As H5N1 influenza continues to circulate in wild birds, and spillover into a wide range of other birds and mammals, it’s difficult to find the right messaging with regard to the risk of transmission to people.

• Historically, H5N1 influenza has had a reported mortality rate of 30-50% in people, but it been a lot lower with the strains currently circulating in most parts of the world.

• Human infections with H5N1 influenza continue to be really rare overall, but they do occur. Generally milder disease doesn’t mean always milder disease, and a small number of fatalities have been reported in the last few years.

• Spillover of this virus into domestic animals (including poultry, cattle and cats in particular) continues to occur. These spillovers create more risk to people given the closer and more frequent human contact with domestic animals, but surveillance has been limited in household animals such as cats and dogs.

Communicating risks in situations like this is challenging, since we want to raise awareness so people recognize that there is some risk and a need to take basic precautions, but at the same time, we want to make sure there’s no panic and that the risks are dealt with in a reasonable manner. The sweet spot between awareness and paranoia is often tough to find with infectious diseases (as the current cruise ship hantavirus cluster also shows, but that’s another story).

A recent report in CDC’s Morbidity and Mortality Weekly Reports describes a case of suspected cat-to-human transmission of H5N1 influenza in California. It highlights some risks that we’ve been trying to message for a few years now.

• The good news is the incident didn’t make the person sick (or at least not sick enough that it got reported. The bad news is that there is evidence that tranmission from the cat occurred at all.

The report describes follow-up of people in Los Angeles County who were exposed to cats that got H5N1 influenza from consuming contaminated raw milk or raw diets.

• There were ultimately nine confirmed feline cases, and ten other suspect cases.
• 139 people exposed to these cats were monitored for symptoms of flu; of those, 30 developed flu-like illness.
• 33 people, including 18 of the people who had signs of upper respiratory tract infection, were tested for H5N1 flu by PCR and all were negative, while 36% tested positive for another respiratory virus (mainly human seasonal flu).

PCR testing mostly detects active infection, where the virus is still present. The challenge with this kind of surveillance is that by the time the cats were diagnosed, contacts identified and notified, and testing performed, the virus was likely to be long gone in people (if it was there at all).  Flu infections tend to have a short incubation period (from exposure to onset of illness), and people don’t shed the virus for very long. The median time from exposure to testing in these individuals was 8 days, which is stretching it for flu, no negative results are not surprising, but can’t entirely rule out transmission.

A complementary testing method is looking for antibodies in blood (serology). Antibodies take time to be produced, but they can stay in circulation for a fairly long period of time. So, someone who was infected a few weeks ago would likely be PCR-negative but antibody-positive. The presence of antibodies tells use there was exposure to the virus at some point, but not when. That’s a big limitation of serology in some situations, but in this case where we suspect the risk of exposure to H5N1 flu other than the known contact with the infected cats is very unlikely, finding antibodies in a person is a pretty solid indication that they were infected by the cat.

Twenty-five (25) of the individuals exposed to the infected cats were tested for H5N1 antibodies, and one was positive – a veterinarian, who had no other identified risk of exposure. They didn’t get sick, but they worked on an infected cat without using any respiratory or eye protection (high-risk contact). That makes it a pretty solid presumptive diagnosis of cat-to-human transmission of H5N1 influenza, even though the person was PCR-negative for H5N1 flu when tested 7 days after exposure (so likely missed the viral shedding period).

You might say “they didn’t get sick, so who cares?” At the individual level, that’s fair, but there are broader issues. This case shows that infected cats do pose some degree of risk to people (which we’ve suspected all along). While this person didn’t get sick, the next person might not be so lucky, based on the dose of virus to which they are exposed, their underlying health, and random quirks of disease.

While the H5N1 virus is still not well adapted to people, the more it’s transmitted between mammals, the greater the risk of it adapting to become better able to infect mammals (including people).

We’re also worried about someone with regular human seasonal flu getting exposed to H5N1 flu at the same time. That creates the potential for recombination, whereby the two flu viruses mix together in the same host, potentially creating a new virus strain with the worst parts of both the seasonal flu virus (i.e. easily transmitted between people) and H5N1 flu (a “new” virus to which there is limited individual and population immunity, and potentially could cause more severe illness).  That’s how pandemic viruses emerge. The odds of that happening are low, but the more the viruses mix in different species, the more that risk increases. Here, a reasonable number of people who were exposed to H5N1-infected cats had confirmed seasonal flu infections, so it’s far from a theoretical risk.

Ultimately this report doesn’t really change the current story much, but it’s documentation of something we had assumed would happen. It reinforces the need to take basic infection control precautions around sick cats that have potentially been exposed to H5N1 flu, to take steps to limit exposure of cats to this virus (like keeping them indoors when possible), and to continue surveillance in this and other species.

And as we saw with cat-to-human transmission of SARS-CoV-2 , veterinarians are at the forefront of this risk.