H5N1 Panzootic
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The more often the virus infects mammals, the greater the risk. It’s a numbers game.
The currently circulating HPAI H5N1 is derived from viruses of the goose/Guangdong/96- (gsGD)- lineage that were first detected in commercially-farmed geese in China in 1996 and have circulated and evolved in poultry. Multiple strains of virus within the gsGD lineage spread across east and southeast Asia in 2003-04, some of which was the result of spread by wild birds (e.g. to Japan and Republic of Korea). In 2005 the first intercontinental wave of transmission of gsGD viruses occurred across Eurasia and into Africa and has been followed by multiple waves of intercontinental spread. Viruses in the gsGD-lineage viruses have evolved into 5th order clades and have formed multiple genotypes. The A(H5N1) virus that emerged in 2020 belongs to clade 2.3.4.4b and has caused numerous outbreaks in wild birds in Asia and Europe, typically during autumn and winter, as well as in Africa, but has persisted year-round in wild birds in Europe since 2021. That same year, HPAI H5 spread across the Atlantic Ocean to North America, where it spread rapidly across the continent in 2022 and southwards to Central and South America
That’s the first time in the history of this virus, or group of viruses, that we’ve seen that global spread on such a scale. It’s a gamechanger.

Complex Relationships

The relationships between birds and mammals, between wild and domestic animals, are complex. H5N1 is traversing many of them. With the introduction of H5N1 clade 2.3.4.4b the host range has extended dramatically. While waterfowl serves as reservoir, migrating birds are spreading the virus all over the world. From millions of wild birds the virus spreads to wild mammals, but also domestic mammals and domestic birds. Sometimes the virus traverses several species, sometimes the virus is transmitted back to wild birds.
It is unclear what the final host species infecting "patient zero" would look like. It could be a pig acting as an influenza virus mixing vessel. Or a cat living in the same household. It could be a mouse contaminating the food. The relevant mutations could develop in "patient zero" by chance after one of the more common infections by chickens or after drinking contaminated raw cow milk.
Some risks are obvious, for example mink farms. But the risk emanating from millions of infected birds and the transmission back and forth between birds and mammals in the wild is difficult to evaluate. As long as the virus spreads in birds around the world, the spillover events into mammals won't stop. And the risk rises with each opportunity for the virus to adapt to mammals.
The number of dead animals is already catastrophic and some species may become extinct. However, H5N1 is far from running out of animals to infect. With Australia there is still an entire continent left to infect. It's a numbers game and we may become overwhelmed by the sheer number of infections.

In Peru and Chile, more than 500,000 wild birds of at least 65 species and more than 20,000 wild mammals of at least 15 species were reported dead, with actual mortality likely many times larger. This mortality is a potential threat to the conservation of several wild animal species. For example, HPAI-H5-associated losses included about 36% of the endangered Peruvian pelican (Pelecanus thagus) population in Peru, about 13% of the vulnerable Humboldt penguin (Spheniscus humboldti) population in Chile, and about 9% of the South American sea lion (Otaria flavescens) population in Peru and Chile.
In summary, despite lacking an accurate estimate of the true impact on wildlife, we are witnessing a panzootic of an unprecedented and enormous scale. This panzootic did not emerge from nowhere, but rather is the result of 20 years of viral evolution in the ever-expanding global poultry population. Given the key role of poultry production in food chains, and the effect on livelihoods, it is logical for countries to prioritize their response towards poultry. However, that wild bird outbreaks are widely neglected, to the degree that we do not even know the order of magnitude of deaths, nor the population and ecosystem consequences, is highly concerning. As a result, the true impact of this panzootic on wild birds may not be recognised for years to come, and some species may never recover.
Wild birds can transmit the virus, but domestic farms can amplify it.

Wild Animals

While millions of wild animals worldwide succumb to H5N1, all that can be done at a larger scale is to remove infected carcasses to slow down the worldwide spread. What happens in the vast wilderness often stays undetected and may surprise us one day.

>> Wild Animals

We estimate the scale of mortality amongst wild birds is in the millions rather than tens-of-thousands reported, through comparison of notification data to accounts literature.
Although little can be done to stop HPAI H5 from spreading to Antarctica and causing mortality in Antarctic wild birds and mammals, there are several detection and response options possible. These include surveillance and accurate documentation of HPAI-H5-associated mortality events, and following guidelines to reduce risk of human-mediated virus spread

Domestic Animals

The large quantities of animals in factory farming in crammed living conditions are a clear pandemic risk, despite dissenting opinions. This risk is negligently exacerbated due to short-term financial interests, even vaccinations are controversial. More than 100 million chickens have already been culled to curb the spread of H5N1. This is however only a small fraction of the poultry kept by humans. In terms of biomass there is far more livestock than wild mammals and far more poultry than wild birds. And avian influenza has started to spread in dairy cattle as well.

>> Domestic Animals

More than 140 million birds have died and hundreds of millions of pounds have been spent in the past year in the US, UK and EU in tackling bird flu, as some experts said continual culling was “morally” wrong.
Livestock make up 62% of the world’s mammal biomass; humans account for 34%; and wild mammals are just 4%. (...) For birds the distribution is similar: poultry biomass is more than twice that of wild birds.
Bird flu is just the tip of the iceberg. Its prevalence in the past two years follows decades of irresponsible practices that cause and spread disease on industrial animal farms.

Contamination and Transmission

There are several ways how influenza spreads, is transmitted, and contaminates the environment. Most intuitive is the respiratory-aerosol route, where exhaled particles are inhaled and infect the airways. The ingestion of infected animals is another way to get infected. A third option is the fecal-oral route. More generalized influenza can be transmitted by fomites, contaminated inanimate objects. While the actual impact is being researched, H5N1 has a tendency to contaminate and persist. Bird feces contaminate the habitats of seals and sea lions at the coastline, but also bodies of freshwater. Recently bird flu has found a new vector in raw cow milk.

The maximum periods for viral survival were observed in samples stored at +4°C in all tissue types and were 240 days in feather tissues, 160 days in muscle, and 20 days in liver. The viral infectivity at +20°C was maintained for a maximum of 30 days in the feather tissues, 20 days in muscle, and 3 days in liver.
During H5N1 virus outbreaks, numerous environmental samples surrounding outbreak areas are contaminated by the virus and may act as potential sources for human and/or animal contamination.
In an experimental challenge study, we found that IAVs maintained in filtered surface water within wetlands of Alaska and Minnesota for 214 and 226 days, respectively, were infectious in a mallard model. Collectively, our results support surface waters of northern wetlands as a biologically important medium in which IAVs may be both transmitted and maintained, potentially serving as an environmental reservoir for infectious IAVs during the overwintering period of migratory birds.
In summary, the feather epithelium contributes to viral replication, and it is a likely source of environmental infectious material. This underestimated excretion route could greatly impact the ecology of HPAIVs, facilitating airborne and preening-related infections within a flock, and promoting prolonged viral infectivity and long-distance viral transmission between poultry farms.
The quantitative importance of the feather excretion route, compared to the respiratory and digestive shedding routes, still needs to be assessed. Nevertheless, although a definitive conclusion is still premature, the intensity of the viral signal detected in the feather fraction identified in dust samples is remarkable. Current data available in chicken suggest that feather particles make up as much as 10% of the total mass of the dust present in poultry houses, underlying the quantitative importance of animal exposure to this type of substrate.
Altogether, these data support the notion that infected duck feather debris are infectious. Persistence of infectivity over time and dispersion of such infectious debris in the environment remains to be assessed, in particular for long-distance contamination and between-farm dissemination.
However, the actual mechanisms of interfarm transmission are largely unknown. Dispersal of infectious material by wind has been suggested, but never demonstrated, as a possible cause of transmission between farms. Here we provide statistical evidence that the direction of spread of avian influenza A(H7N7) is correlated with the direction of wind at date of infection. Using detailed genetic and epidemiological data, we found the direction of spread by reconstructing the transmission tree for a large outbreak in the Netherlands in 2003. We conservatively estimate the contribution of a possible wind-mediated mechanism to the total amount of spread during this outbreak to be around 18%.
A comparison between the transmission risk pattern predicted by the model and the pattern observed during the 2003 epidemic reveals that the wind-borne route alone is insufficient to explain the observations although it could contribute substantially to the spread over short distance ranges, for example, explaining 24% of the transmission over distances up to 25 km.
H5N1 virus lost infectivity after 30 min at 56°C, after 1 day at 28°C but remained viable for more than 100 days at 4°C.
The virus survived up to 18 h at 42 °C, 24 h at 37 °C, 5 days at 24 °C and 8 weeks at 4 °C in dry and wet faeces, respectively.
The survival time of the avian influenza A(H5N1) virus on plastic surfaces was ≈26 hours and on skin surfaces ≈4.5 hours, >2.5-fold longer than other subtypes. The effectiveness of a relatively low ethanol concentration (32%-36% wt/wt) against the H5N1 subtype was substantially reduced compared with other subtypes. Moreover, recombinant viruses with the neuraminidase gene of H5N1 survived longer on plastic and skin surfaces than other recombinant viruses and were resistant to ethanol. Our results imply that the H5N1 subtype poses a higher contact transmission risk because of its higher stability and ethanol resistance, which might depend on the neuraminidase protein.
These results indicate that deposited virus on milking equipment could remain infectious for long periods of time, posing a potential risk to humans as well as contributing to cow-to-cow transmission. Typically there is only 10-15 min between milking sessions with shared milking equipment, thus virus from an asymptomatic infected cow could remain on the material for multiple rounds milking sessions. These results are currently being validated with bovine H5N1 virus and preliminary data suggests a similar trend in stability, with <2 log="log" decay="decay" at="at" 1="1" hour="hour" of="of" incubation="incubation" 70%="70%" RH="RH" on="on" both="both" surfaces="surfaces">
These data highlight HPAIV persistence at low temperatures, so presenting a greater infection risk to avian species during the cooler months in temperate latitudes, especially in the case of clade 2.3.4.4 H5Nx HPAIVs to waterfowl with subsequent incursion risks for farmed poultry. Our statistical data, using pairwise comparisons of virus DT values and extrapolated extinction times at 4 °C and 20 °C, (...), revealed that, in many instances, the virus survival (stability) of each isolate was significantly different from the others. (...) Interestingly, heat treatment may provide an alternative to chemical disinfection, thereby giving additional importance to the outcomes of viral temperature stability investigations.
Even if this never becomes a pandemic of people, it is a horrible disease for the animals