#17,581
Not quite two months ago we looked at the UK HAIRS Initial Risk Assessment of the threat of human infection in the UK from exposure to infected non-avian wildlife. At that time, this expert group assessed the risk of human infection in the UK as VERY LOW.
As with nearly all emerging disease risk assessments, experts are forced to work with limited and often delayed information, and the knowledge that the pathogen(s) in question continues to evolve.
With H5N1, there are scores of genetically distinct H5Nx sub-clades in circulation around the globe, and untold variants within them, and any one of them has the potential to evolve into a more dangerous variant.
Two weeks ago the UKHSA Announced 2 More (Asymptomatic) H5N1 Cases among poultry workers in the UK, and in recent weeks we've seen outbreaks of H5N1 affecting cats in Poland, cats in South Korea, 20 fur farms in Finland, and dogs and cats on a farm in Italy.
Human infections, thankfully, remain very rare.
However ominous all of this may seem, so far H5N1 doesn't yet appear to have the `right stuff' to spark a pandemic. And it is even possible there is some undefined `species barrier' that prevents that from happening.
That, of course, could change.
Yesterday the UK HAIRS group released an updated risk assessment, taking many of these recent events into consideration. Based on what they know, and the relatively narrow scope of this assessment (spillover of H5N1 to humans in the UK), their conclusions have not changed.
I've only reproduced the summary. Follow the link to read their rationale for their conclusions. I'll have a brief postscript after the break.
Research and analysis
HAIRS risk assessment: avian influenza A(H5N1) in non-avian UK species
Updated 27 July 2023Date of this assessment: July 2023
Version: 2.0
Reason for the assessment: first confirmed detections of avian influenza A(H5N1) in non-avian UK species (for example red foxes, Eurasian otters, harbour and grey seals); concerns for mammalian adaptation of avian influenza A(H5N1) virus.
Completed by: HAIRS members
Non-HAIRS group experts consulted:UKHSA’s Acute Respiratory Infections team
Selene Huntley (Public Health Scotland)
Christopher Williams (Public Health Wales)
Date of initial risk assessment: June 2023
Reason for update: inclusion of new detections of avian influenza A(H5N1) in humans in the UK, and domestic animals (cats and dogs) in Europe.
Information on the risk assessment processes used by the HAIRS group can be found on GOV.UK.
Summary
Avian influenza (AI) is an infectious disease of birds caused by the influenza A virus. Birds are the hosts for most AI viruses (AIV), and a variety of influenza subtypes, including AI A(H5N1), can be found in birds, particularly in waterfowl and shore birds. Domestic poultry are especially vulnerable, and the virus can rapidly cause epidemics in flocks. In October 2020, highly pathogenic AI A(H5N1) clade 2.3.4.4b was detected in Europe, after re-assortment of AI A(H5N8) with wild bird lineage N1 viruses. Since October 2021, AI A(H5N1) clade 2.3.4.4b has become the dominant AI subtype detected in wild and captive birds across Europe and the UK, with a relatively stable genotype.
The virus has now been reported from wild birds and poultry across Africa, Asia, North and South America, Europe and the Middle East. Globally, there has been an increased spillover to non-avian species including wild and captive terrestrial and marine mammals, and domestic pets, likely as a result of the increased environmental pressure from the thousands of wild birds infected, rather than as a result of increased viral affinity for mammalian cells.
Positive detections of AI A(H5N1) have been identified in a range of animals, mostly from the Carnivora family. In the UK, and as of March 2023, retrospective testing of samples collected since 2021 revealed positive detections in red foxes, Eurasian otters, common and grey seals, harbour porpoises and common dolphins, as well as a single event in captive South Africa bush dogs (Speothos venaticus). These were the first detections of AI A(H5N1) in non-avian UK species. Although these findings appear sporadic and isolated incidents, potential mammal-to-mammal transmission of AI A(H5N1) has recently been described in farmed mink in Spain, with genetic analysis revealing an uncommon mutation (T271A) in the PB2 gene which may enhance influenza A viral activity in mammalian host cells.
Detections of AI A(H5N1) in domestic cats (in France, Italy and Poland) and 5 dogs on a single poultry establishment (in Italy) have been reported, although such instances remain rare. The Poland cases have created a lot of interest as the source of infection has not been identified and the companion animals concerned (33 tested positive to date) were from multiple sites across Poland, were both indoor and outdoor cats, some exposed to raw pet food or wild birds and others not. Sequences of viral isolates from infected cats contain the common mutation, E627K in the PB2 gene, as well as the less common K526R, which has been detected in wild bird viral isolates.
More recently, Finland reported that 12 fur farms tested positive for AI A(H5N1). Most farm blue foxes, but also silver foxes, mink and raccoon dogs. The farms house between 3,000 and 50,000 animals. Generally, the first signs of infection were an increase in mortality in a few animals, as well as lethargy, neurological symptoms and diarrhoea. The source of infection is not yet known, although in one instance, a mass mortality event in black headed gulls was reported near one of the farms. Sequencing has been completed, and there were 2 markers in the cleavage site of increased mammalian cell affinity found in one sequence. All sequences aligned with those of wild birds, particularly strains found commonly in Europe in gulls.
Where AI A(H5) subtypes circulate in poultry or wild birds, then sporadic human cases should not be unexpected in people with close contact or high levels of exposure. This is particularly evident for Asian lineage AI A(H5N1), with 868 human cases, including 457 deaths, being reported from 21 countries between January 2003 and January 2023. Where Eurasian lineage AI A(H1N1) clade 2.3.4.4b is concerned, from 2020 to the end of December 2022, 6 human cases were reported, globally. All these cases had exposure to infected poultry. To date, there are no reported transmission events of AI A(H5N1) from non-avian infected species to humans.
This risk assessment will focus predominantly on AI A(H5N1) clade 2.3.4.4b as this is the dominant subtype detected in wild and captive birds across Europe and the UK at the time of writing.
Assessment of the risk of infection in the UK
Probability
General UK population: Very Low
The probability of infection would be considered Low for those exposed to infected live or dead non-avian species.
Impact
The impact on the general UK population would be considered Very Low, while it would be considered Low for higher risk groups (for example individuals with occupational exposure to infected non-avian species and/or immunocompromised or paediatric cases).
Level of confidence in assessment of risk
Satisfactory.
The majority of mammal cases are of the order Carnivora. While they may not all be recognised as commonly predating live or dead avian species, direct contact with a contaminated environment is also a possible transmission route. Without direct observational studies or environmental sampling in areas in the vicinity of known infection, it cannot be proven that mammal-to-mammal transmission is not occurring.
Given human detections of AI A(H5N1) clade 2.3.4.4b are rare, there is a paucity of evidence on what risk factors may increase disease susceptibility, severity and poorer clinical outcomes in human cases. For those cases reported, clinical disease has ranged from mild to severe. There is possible under-ascertainment of cases, particularly in instances where mild disease manifests.
Actions and recommendations
While there have been no reported incidents of people becoming infected as a result of direct contact with an infected wild mammal, captive mammal or companion animal, procedures to reduce human exposure to non-avian species potentially infected with AIV should be implemented, to minimise the risk of zoonotic infections. Members of the public should be discouraged from touching dead or sick animals. Pet owners should be encouraged to speak to their private vet if they are concerned about clinical signs in their companion cat, dog or ferret and are aware it has had contact with wild birds. If a member of the public observes an animal they deem in danger or distress, they should contact an appropriate helpline for advice and assistance (for example the RSPCA in England and Wales, the SSPCA hotline in Scotland and the USPCA in Northern Ireland).
Individuals who come into close contact with wildlife potentially infected with AIV as part of their work should be trained in the use of appropriate personal protective equipment (PPE), including aerosol-related respiratory precautions, to mitigate against the risk of zoonotic infections. Further information on working with AIVs is outlined in guidance published by the Health and Safety Executive (1).
In Great Britain, the APHA wildlife expert group maintains close interactions with non-governmental organisations (NGOs), including rescue centres. Where appropriate, NGOs should be encouraged to collect and submit samples from sick or dead non-avian wildlife to APHA Weybridge diagnostic laboratories for testing, of which AI A(H5N1) should be a considered differential, so as to be alerted to changes in viral epidemiology and potential risk. Additional information can be found on GOV.UK:
- guidance on how veterinarians, diagnostic laboratories, wildlife rehabilitators and research establishments can submit samples for testing (2)
- technical guidance for private laboratories, organisations and individuals in Great Britain involved in testing samples from animals for Influenza A virus (3)
- existing risk assessments for specific AIV subtypes
As a general rule, zoonotic viruses aren't capable of sparking a pandemic until quite suddenly, they do.
- The 2009 H1N1 swine virus kicked around in pigs for at least a decade before suddenly stumbling upon the right combination of mutations that allowed it to spread in humans.
- The same is likely true for SARS-CoV-2, although our knowledge of its origins remain murky.
- In 1968, when the world was dominated by H2N2 influenza (which emerged as a pandemic virus in 1957, supplanting H1N1), an avian H3N2 virus emerged in Hong Kong and rapidly spread around the world, killing a million people. Since then it has become the longest running, and deadliest, seasonal flu on record.
And of course, H5N1 is far from the only virus with pandemic potential we are watching.
COVID could reinvent itself in a human, or non-human, host. MERS-COV is still endemic in camels in the Middle East and occasionally spills over into humans. And the CDC currently follows 23 zoonotic influenza viruses with at least some pandemic potential.
While I'm not convinced that H5N1 will spark the next pandemic, it has to be viewed as a legitimate contender. Regardless, we live in a threat-rich environment, and another pandemic is inevitable.
It's just a matter of time.
