As concerns about an outbreak of canine infectious respiratory disease in the US continue, we’re still at a point where media hype massively outweighs any true data. Not much new has been reported recently. If anything, I’d say we’re hearing more about things being stable in different areas, that investigations haven’t turned up anything beyond the usual suspects, and the typical messaging to use common sense but relax.

One thing that is getting some press is a suggestion that a rather bizarre little bacterium might be involved in some of the current canine illnesses. “Might” is the key word though. At the risk of having to eat my words later, I’d guess this bug is probably not going to pan out to be a driver of widespread disease – it’s possible, but there’s a long way to go before we can say that with any confidence. In the meantime, let’s recap what we know:

In the spring of 2023, the New Hampshire Veterinary Diagnostic Lab reported they were investigating a potentially novel organism as a cause of respiratory disease in dogs. I remember reading about it in a taxi on my way to the airport in DC; I thought it was interesting, but in my experience, the vast majority of “new pathogens” end up being commensal organisms (i.e. also present in lots of healthy dogs) or otherwise not panning out to being relevant. But, I never totally discount the possibility, and was glad to see it investigated. The initial (and I think only) report involved a pretty small number of dogs. They found snippets of DNA that were similar to IOLA KY405 in 21/31 samples. Their latest update is here.

What on earth is IOLA KY405?

It’s hard to say. As far as I know, it’s only previously been reported in two papers from the same lab in Japan, where it was found in samples from humans with respiratory disease. It’s reported to be a bacterium with a very small and bizarre genome.

• The first study (Fukuda et al. 2014) reported finding gene sequences from IOLA KY405 in a lung fluid sample from one person, then followed up by finding those DNA bits in samples from 6/386 samples from other patients with respiratory disease. Some unique aspects of this bacterium are a very small genome, similar to Mycoplasma  (just over 300K base pairs; for reference, staphylococci have about 2.8 million base pairs), and a very high AT content (about 80%).

• In the second study (Fukuda et al. 2021), they presented the whole genome sequence of the organism. They also used PCR to look for it in samples from more people with respiratory disease, and got positive results in 2.7% of about 500 samples. Eight of the 11 positive patients had significant underlying disease, and five were being treated with corticosteroids or immunosuppressants. So, these individuals had lots of other excuses to have respiratory disease or to be infected with something that’s minimally pathogenic.

Someone with more background in genomics would need to assess the papers to know how confident we can be in the results. If they are real, then the researchers have found a small bacterium that’s similar to Mycoplasma, which maybe isn’t surprising since some Mycoplasma are able to infect lungs (but more often are present as normal respiratory tract inhabitants.)

What we’re still lacking is 1) actually growing the bug to confirm its existence, and most importantly, 2) context. Finding DNA from this bug in a small percentage of people with respiratory disease is interesting, but could it be just as common in healthy individuals and just part of our normal microbiota? I don’t think we can say either way at this point.

When something’s only reported by one group over a long period of time, it raises the question of why. Is one group just way ahead of the curve, or is this something that other people have tried to find but have been unable to replicate the results (or have looked at and dismissed as not being worth investigating)? Publication bias is a big problem in cases like this. If other groups have put in a good effort to investigate this and found nothing, odds are high we wouldn’t find out because there’s a tendency to not publish “negative” results, even though those data are really important. So, we have no idea if there are only two papers because only one group is looking for it, or whether lots of other people have tried and failed to find anything similar.

Genome-based pathogen discovery is an established and effective method. It looks at all the genetic bits we can find in a sample, then tries to assemble them into something interpretable, and then we try to figure out what it actually all means. It’s challenging because we have a vast population of viruses and bacteria that are normal inhabitants in our bodies and those of animals. Most are harmless. Many are beneficial. Some can cause disease. Sorting out into which category a new organism fits takes a lot of work, and is rarely straightforward.

We’ve been lead down the wrong path many times before by reports of a “new” organism found in sick animals (e.g. the panic about canine circovirus). People freak out, start testing more sick animals, find it, and freak out more. However, when the science catches up with the hype, we often realize that we can find the bug in the same percentage of healthy animals, and it’s just a normal inhabitant that we’ve recently discovered, versus something new that is causing disease. With modern molecular techniques, our ability to find something often surpasses our ability to understand it.

While it sounds like I’m downplaying the relevance of this finding, that’s not my intention. I suspect IOLA KY405 is a real organism, I just need a lot more convincing that it’s relevant to disease (in people or animals). In an ideal world, the New Hampshire lab and others would be investigating this robustly, including field studies in dogs, to deterimine what the real story is. Lack of funding for companion animal infectious disease research usually slows these to a crawl. The report from the New Hampshire lab adds good context:

• “It is important to note that this is a preliminary finding, and under normal circumstances of a study we would not release these findings. The technology and methods used by the HCGS include cutting edge metagenomic sequencing, and multiple bioinformatic pipelines that are uncommonly utilized in veterinary medicine. Additionally this is an uncommonly studied group of bacteria. There are multiple experiments that need to be run in order to clarify correlation vs. causation, and this gives reason for pause in releasing the findings. However, the syndrome is ongoing and there may be an opportunity to benefit animal health as we continue to validate these initial findings. There is a chance that this preliminary data is disproven with further study, but at this point it does appear that the bacteria we have identified is a potential causative agent.”

Those disclaimers are key, but unfortunately are usually left out of the media reports.

This is an important but very preliminary finding that needs to be studied. However, we also have to realize that most findings like this don’t turn out to be anything big (or anything at all). We can’t dismiss the potential and it’s great to see the work being done, but we need to make sure that we don’t jump from a preliminary finding of some unusual DNA sequences to “here’s the answer!” which is what human nature wants us to do.