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A lot of infectious disease events get over-hyped by the media, which makes it a bit surprising that this case has flown a bit under the radar. It’s not a sign of an impending “influenza apocalypse,” but it’s a warning sign that more may be going on lately with flu viruses than we’ve been able to observe directly.

The CDC has confirmed a case of H5 influenza infection of a person in Missouri who had no reported contact with animals of any kind. The virus has only been identified as H5 or H5Nx, which means they have not confirmed the N-type, so we can’t say if it’s the same as the H5N1 influenza that has been circulating in wild birds since 2022, or in dairy cattle in the US since spring 2024. It’s surprising that the N-type has not been determined yet, since the infection was detected over 2 weeks ago – but knowing the strains that are circulating in the US right now, I’d say it’s almost certainly H5N1. (Sometimes sample quality can impede the effectiveness of molecular diagnostics too.)

Human H5N1 infections linked to the ongoing massive multiyear avian influenza outbreak have been rare. There have been just 14 reported H5 infections in people in the US so far in 2024, despite a huge amount of potential exposure, particularly among livestock and poultry workers. All previous human infections have been linked with direct and close contact with infected animals.

Rare spillover infections like these are largely expected when there’s lots of disease in animals. The worry is the potential for the virus to change to become amenable to human-to-human spread, so finding a human infection like the one in Missouri with no direct link to animals raises a lot of concern. The source of exposure in this case has not been determined. Details are sparse, but the person was reportedly hospitalized and recovered, and H5N1 testing was done as part of ongoing surveillance.

How could a person get H5N1 without animal contact?

  • Unreported animal contact, possibly due to incomplete history taking, or poor recall or unwillingness to report contact on the part of the patient for some reason)
  • Contact with a surface contaminated by an infected animal
  • Ingestion of contaminated food products

We hope the source of infection in this case was one of those. Hopefully they queried all animal contacts, not just birds and cattle, since we’re also concerned about infection from susceptible species that can bridge bird, cattle and and human populations (particularly cats).

Otherwise, we get concerned about the last option:

  • Contact with another infected person

As has been pretty common, details have been slow in being released. More information is needed about the person’s history, including whether the person had any human contacts that were high risk for exposure (e.g. worked with infected animals), and the genome of the virus to see if it’s consistent with the circulating avian strain, the strain that jumped to dairy cattle, or something different, and whether the strain has any genetic markers that indicate it could be more adept at spreading person-to-person. Missouri hasn’t reported H5N1 in cattle, but it’s circulating in wild birds, with spillover into poultry and backyard chickens. Missouri doesn’t have a huge dairy industry, but there are still lots of dairy cattle around and it doesn’t sound like there’s been much testing (a report in July said that only 17 of the state’s approximately 16,000 dairy cattle had been tested), so we can’t rule out local dairy cattle (or unpasteurized milk) as a source either.

Hopefully this is an oddball infection that died out when the person recovered, i.e. they got infected somehow but didn’t pass it on to anyone else. However, even if that’s the case, this event demonstrates why we need to have comprehensive and nimble influenza surveillance.

  • If the infection is indirect linked to dairy cattle (by finding the dairy cattle strain in the person), it shows again that the US has to take dairy cattle infections more seriously. H5N1 in dairy cattle should be containable with short term but aggressive movement restrictions, testing and infection control measures – short term pain for long term gain. Fewer infected farms are being reported lately, which is great, but it’s still spreading across the country. The longer the outbreak lasts, the greater the chances of interspecies spillover and for the virus to adapt to a new host.
  • If the infection is somehow linked to wild birds, that’s a tougher situation, since controlling the virus in wildlife populations is challenge, to put it mildly.

This case was detected as part of surveillance program. That’s great, in that surveillance found something important and led to an action: an investigation of possible sources and a warning that there could be more. The not-so-great part is that few people with flu-like disease get tested at all, including for H5N1 influenza. If human-to-human spread is occurring, it could easily slip under the radar if there’s insufficient testing happening. That’s particularly true if most infected people only get mild disease, as they’re even less likely to get tested. We don’t know whether this was a lucky detection of a very rare situation, or a more common problem that’s been flying under the radar. Only more time and testing will tell us that.