As H5N1 continues to spread in birds, and spillover into a wide range of animals, zoonotic risks are hard to message.

• Historically, H5N1 has had reported mortality rates of 30-50%, but it seems to be a lot lower with the strains we’re currently seeing.

• Human infections are really rare, but they occur. Generally milder disease doesn’t mean always milder disease and fatalities have been reported.

• Spillover into domestic animals continues to occur and creates more risk given closer animal-human contact, but surveillance has been limited.

Messaging risks for situations like this a challenging since we want to raise awareness and get people to recognize there is some risk and a need for basic precautions. At the same time, we want to make sure there’s no panic and the risks are dealt with reasonably.

The sweet spot between awareness and paranoia is often tough to find with infectious diseases (as the current hantavirus outbreak also shows, but that’s another story).
A recent report in CDC’s Morbidity and Mortality Weekly Reports describes suspected cat-human transmission of H5N1 and highlights some risks that we’ve been trying to message and address for a few years.

• The good news…it didn’t cause disease (or at least disease that was serious enough to be reported.

• The bad news….it occurred.

The report describes follow-up of people in LA County that were exposed to cats that got H5N1 from raw milk or raw diets.

• There were nine confirmed feline cases (and 10 other suspects).
• 139 people exposed to these cats were monitored for symptoms of flu. 30 developed flu-like disease.
• 33 people, including 18 of the people that had symptoms of upper respiratory tract infection, were tested by PCR and all were negative.  36% tested positive for another respiratory virus, mainly human seasonal flu.

PCR testing requires active infection, where the virus is still present. The challenge with surveillance is that by the time the cat is diagnosed, contacts are identified, contacts are notified and testing is performed, the virus may be long gone.  Flu infections tend to have a short incubation period (the time from exposure to the onset of disease) and people don’t shed the virus very long, so false negative results are not surprising with this type of testing approach. Here, the median duration from exposure to testing was 8 days, which is stretching it for flu.

A complementary method is testing blood for antibodies. Antibodies take time to be produced but they stay in circulation for a prolonged period of time. So, someone that was infected a few weeks ago would likely be PCR negative but have antibodies. The presence of antibodies tells use there was exposure to the virus at some point, but not when. That’s a big limitation in some situations but when we think the risk of exposure outside of the known event (contact with the sick cat) is very unlikely, finding antibodies in a person provides a pretty solid indication that they were infected by the cat.

25 people were tested and one was positive.

• This was a vet who had no other identified risk of exposure. They weren’t sick but had worked on an infected cat without any respiratory or eye protection. So, the presence of antibodies, the known contact and the high-risk contact (inadequate PPE) make it a solid presumptive diagnosis of cat-human H5N1.

Tying discussion of PCR and serology together….the vet who had antibodies against H5N1 had a negative H5N1 PCR test, with the sample taken 7 days after exposure.

You might say ‘they didn’t get sick, so who cares?’. At the individual person level, that’s fair. However, there are broader issues.

Cat-human transmission shows that cats pose some degree of risk. While this person didn’t get sick, the next person might not be so lucky, based on the dose of virus they are exposed to, their underlying health and random quirks of disease.

In the bigger picture, virus is still not well adapted to people but the more it infects and passes between mammals, the greater the risk of it adapting to become better able to infect mammals (including people).

In the even bigger picture, we’re worried about a scenario where someone has human flu and gets exposed to H5N1 at the same time. That creates the potential for recombination, whereby the two flu viruses mix, potentially creating a virus with the bad aspects of both the human flu virus (easily transmitted between people) and H5N1 (new virus for us so our immunity is limited, potentially increased severity).  That’s how pandemic viruses develop. Odds of that are low, but the more this virus mixes in different species, the more that risk increases. Here, a reasonable number of people that were exposed to infected cats had confirmed seasonal flu infections, so it’s far from a theoretical risk.

So, this report doesn’t really change the story too much, but it’s documentation of something we had assumed would happen, so it reinforces the need to take basic infection control precautions, to limit exposure of cats and to continue surveillance.

And….as we saw with SARS-CoV-2 vets are at the forefront of risk.