As H5N1 avian influenza continues to spread in wild birds and spills over into domestic birds and mammals of many kinds, we’re becoming more aware of the risks to domestic mammals and there are more questions about test selection and interpretation. Fortunately, testing for H5N1 influenza is relatively straightforward.

• For cats and dogs, the recommended samples for testing are typically oropharyngeal swabs, plus or minus nasal swabs (plus or minus other tissue samples of the animal is deceased. 

What tests are currently being run by veterinary diagnostic labs?

PCR is the most accessible and useful test; diagnostic labs basically offer two types of influenza PCR: matrix / pan-influenza A PCR, and strain-specific PCRs (see below). Different commercial labs offer different tests or combinations of these tests, and the tests offered may also vary by species (i.e. what’s routinely done for dogs can be different from cats). Test offerings may also change over time as labs adapt to the ever-changing situation with flu in different populations. If influenza is a consideration in your patient, check with your lab regarding which tests they will run (particularly if you are submitting samples for a respiratory PCR panel) and how to interpret the results, including whether or not the test will detect H5N1 flu if that’s a concern.

-

Take home message

• Talk to your lab to know what they can (and can’t) do in terms of testing for H5N1 flu, and follow up testing.
• We can’t just stop at “flu positive.” Any such result needs to be scrutinized to make sure we know the strain (or strains) involved.

The annual flu epidemic has started in the Netherlands, the RIVM and Nivel said on Wednesday. And that is visible in the increasingly crowded hospitals and at schools where teachers are struggling to fill rosters and cover for sick colleagues.

The number of people going to the doctor with flu-like symptoms increased sharply in recent weeks. Official flu diagnoses also increased dramatically. The RS virus is also circulating in the country at the moment.

“Because of this combination, it is busier now than last year,” Esther Cornegé-Blokland, chairwoman of the Dutch Association for Clinical Geriatrics (NVKG), told NOS. “We are in a simmering crisis.” Elderly people are extra susceptible to both the flu and the RS virus. “We have shortages anyway - too few staff, too much demand - and with a peak like this, the bucket in elderly care quickly overflows. We can still help patients, but it is under pressure.”

They wrote:

Thus, while A(H5N5) viruses are comparably uncommon, their high virulence and mortality potential demand global surveillance and further studies to untangle the molecular markers influencing virulence, transmission, adaptability, and host susceptibility.

The superpower of influenza A viruses is their ability for different subtypes to co-infect a host, swap genetic material, and generate a new `hybrid' virus; a reassortant.  This reassortment can generate new genotypes, or - if the HA and NA are involved - a new subtype. 

Reassortment - or Antigenic`Shift' - can produce abrupt changes in the behavior of the generated hybrid.  Most are evolutionary failures, unable to compete with its parental strains. But every once in awhile, a new, `improved', virus emerge.  

As any virologist will tell you; `Shift Happens'. 

Reassortment is the process that enabled an avian H5N1 virus (B3.13) to infect cattle, and has recently produced a more virulent D1.1 genotype, which is spreading rapidly across the nation.  It produced a new H5N9 subtype in California poultry, and it could potentially lead to a hybrid of seasonal and avian flu sometime in the future (see Preprint: Intelligent Prediction & Biological Validation of the High Reassortment Potential of Avian H5N1 and Human H3N2 Influenza Viruses).

Today we have a report, published this week in Emerging Microbes & Infections, of the discovery of an HPAI H5N2 clade 2.3.4.4b virus in Egypt, one that came about through the merger of the H5N1 virus and the ubiquitous, and highly mutable, LPAI H9N2 virus. 

We've often discussed the role that H9N2 has played in the creation of some of the most dangerous HPAI viruses, including H5N1, H5N6, H10N3, and H7N9 (see Transboundary & Emerging Dis.: The H5N6 Virus Containing Internal Genes From H9N2 Exhibits Enhanced Pathogenicity and Transmissibility).

While much as been made over the fact that humans may have some limited cross-immunity to the N1 component of H5N1, a new subtype - sporting an N2 or an N9 surface gene - might prove far more problematic. 

-

While the world seems to be focused on HPAI in North America, this should remind us that H5Nx viruses are occurring all around the globe, and that a new threat could emerge anytime, and from just about anywhere. 

I’m not commenting on every new report of H5N1spillover into a domestic animal because it’s not really news anymore. That doesn’t mean it’s not concerning. It definitely is. However, we expect these spillovers to continue and were going to see continued cases as long as this virus is circulating in wild birds, or, in the US, in dairy cattle.

Despite that, a recent case in Oregon highlights something important. Most reported infections in cats have been severe disease, usually with neurological involvement. We’ve been unclear whether this is because cats typically get severe neurological disease when they are infected or whether we tend to only test cats with severe disease. The fraction of milder disease is unknown and that’s really important for considering testing, either of clinical cases or surveillance testing.

-

Should we consider any outdoor/raw fed cat with any signs of respiratory disease flu suspects? Maybe. It’s certainly possible that H5N1 can also cause typical flu-like disease/upper respiratory infection. So, I’d recommend not completely discounting it in any case, but paying particular attention the more severe the disease is.  

As with most emerging diseases, it’s a fluid environment and it’s tough to figure out where to draw the line, balancing protection and practicality. As we learn more, that line will likely move so we must keep an eye on new developments but take reasonable measures in the interim. Personally, I’m always a ‘test more’ and ‘err on the side of being more aggressive at the start and then de-escalate’ but there’s also a practical limit in how far we can go.