We have different  approaches to rabies in dogs and cats versus humans. The ultimate goal is still the same: preventing this almost invariably fatal infection. However, between humans and animals there are differences in who we target for vaccination, frequency of vaccination, utility of rabies antibody titres, and how we respond to potential rabies exposures, to name a few.

There are good discussion points for all of those, but today I’ll focus on how we deal with rabies antibody titres.

What is a rabies titre?

A rabies titre is a test that measures the amount of anti-rabies antibodies in a person or an animal’s blood. In general, antibodies indicate whether an individual’s immune system has responded to either infection or vaccination; in the case of rabies, because infection is almost always fatal, a titre usually indicates response to a vaccine.  The higher the titre, the more antibodies are present, which usually means a stronger response.  We can periodically recheck an individual’s titre to see how long those antibodies persist over time.

However, interpreting the test results can be a challenge.

While we have reasonable cutoffs for what titre we think indicates a good response to a rabies vaccine, we don’t truly know what is a “protective titre” –  because that would involve testing titres and then seeing which individuals get rabies after being exposed. That’s not the type of research that’s ever going to be done in people (and rarely even in animals, due to risk, ethics and expense, among other things).

Rabies titre monitoring in people

Traditionally, it has been recommended that individuals at higher risk of rabies exposure (like veterinarians and animal control personnel) have their rabies titre checked every 2 years, and that they get a booster vaccine if their titre is below the recommended cut-off (although compliance with that is pretty low).  However, in 2022 the US CDC’s Advisory Committee on Immunization Practices (APIC) updated their recommendations for the prevention of human rabies.  Under the new guidelines, veterinarians fall under category 3 “people who interact with, or are at higher risk to interact, with mammals other than bats that could be rabid, for a period longer than three years after they receive PrEP” (PrEP stand for pre-exposure prophylaxis, which simply means pre-exposure vaccination). The recommendation for individuals in this group is to either have their titre checked 1-3 years after their initial 2-dose vaccination series (with a booster if the titre is low) or get a one-time booster 3 weeks to 3 years after their initial vaccination series. Routine repeat testing every two years is no longer recommended, presumably because they’ve found over time that the vast majority of people who respond to the vaccine initially will have a very good titre for a long time (because human rabies vaccines are very good vaccines).

Rabies titre testing in dogs and cats

We approach titre testing in pets differently and more cautiously than in humans. While not cheap, we can measure rabies titres in dogs and cats and we have a cutoff for what is considered “acceptable” in terms of demonstrating response to previous vaccination.  However, as discussed above, an acceptable titre is not a guarantee of protection against infection if an animal is exposed to rabies.  (Also, while there are some excellent rabies vaccines available for pets, there are a lot more rabies vaccine products for pets than there are for people, and they are not all of equal quality.)

The best way to ensure pets are protected is to use a high-quality vaccine, and vaccinate them according to the manufacturer’s instructions, because research has been done to demonstrate  that this will actually protect the pet from (experimental) infection with rabies.

Many jurisdictions where rabies is being controlled require pets (or at least dogs) to be currently vaccinated against rabies, which typically means  vaccination every 1-3 years depending on the vaccine product used. Titres are not typically considered equivalent to vaccine status, and usually have no influence on what is done in response to rabies exposure in a pet (e.g. if a dog is overdue for its rabies vaccine, it doesn’t matter what its rabies titre is, it is managed the same as any other exposed overdue pet, which often means a long quarantine period (months) at a minimum).

Why do we continually revaccinated dogs/cats against rabies, instead of periodically measuring rabies titres like we do in people?

Part of the reason for this seemingly very cautious approach to protecting pets from rabies prior to exposure is that we don’t have proven post-exposure prophylaxis for dogs and cats like we do in people. If a person reports exposure to rabies, we know how to administer post-exposure prophylaxis such that we can provide virtually 100% protection from infection, whether the person is vaccinated (easier) or unvaccinated (harder, but still extremely effective).  We expect that vaccinated individuals would be able to report most potential exposures and get post-exposure prophylaxis.  Pre-exposure vaccination helps reduce the risk associated with any unknown or inadequately addressed rabies exposures that may occur because these individuals are in higher-risk positions, but even a person with an adequate rabies titre should still receive post-exposure prophylaxis to be confident that infections will be prevented.

For dogs and cats, revaccination after an exposure is still highly recommended / required, whether the animal is currently vaccinated or not, just as post-exposure vaccination is recommended in exposed people. We have more confidence in being able to protect a vaccinated vs unvaccinated animal this way, so vaccinated animals usually have lower or sometimes no requirements for quarantine as long as they’re revaccinated in time.  Unfortunately though, we have no proven post-exposure treatment in pets, so we can’t be as confident in the protection provided as we can be in people.

We also have less confidence in identifying rabies exposures in animals (because pets can get into all sorts of trouble when we’re not looking!).  Therefore, we’re therefore more reliant on vaccination as the main line of defense against rabies in pets. If we had proven post-exposure regimens for dogs and cats, and we had a way to be very confident that we’d identify all exposures, using an identical approach to that for humans would make sense. Since we don’t, and since rabies is almost invariably fatal (and since one infected pet can potentially expose lots of other animals and people), the default is to err on the side of vaccination.

Rabies vaccines are relatively cheap (much cheaper than titres), very safe and effective.  The downsides associated with regular revaccination are outweighed by the potential downsides of taking a titre-based approach when we have little data, no proven post-exposure regimens and limited confidence in identifying all potential exposures in pets.

As canine flu causes another (and particularly impressive) round of outbreaks in the US, a lot of questions arise. A big one involves vaccination.

I won’t go over the whole “what is canine flu?” spiel in this post, but I’ll give a quick overview of why we care about it. It’s a highly transmissible virus that acts… well… like flu does in people. It can cause disease in dogs ranging from mild to fatal. The mortality rate is hard to estimate but it’s probably 1-2%. It was ~2% in our Canadian outbreak of canine influenza in 2018 and we had really intensive surveillance, so it’s probably a pretty accurate number. Deaths are most often reported in older dogs. Dogs with underlying heart or lung disease are presumably at higher risk for mortality too. The same might apply to brachycephalic breeds (squishy faced breeds like bulldogs) since they are more prone to respiratory complications. Like human flu, deaths in otherwise healthy, younger individuals are rare but can occur.

Flu outbreaks are a big problem, and that can be a bigger issue in dogs than people, because we don’t have the same degree of seasonal flu every year in dogs. In humans, there’s a lot more population immunity because of repeated exposure and vaccination. Most dogs in North America have neither been exposed nor infected, so they’re ripe-for-the-picking immunologically.

Obviously there’s a canine flu vaccine, since that the topic du jour…

Yes, we have a couple of canine flu vaccines. They can be for the H3N2 strain alone, or H3N2 and H3N8. H3N2 is the currently circulating canine flu strain. It’s an avian-origin strain that has become adapted to dogs and entered the US from Asia in 2015 (and repeatedly thereafter). H3N8 canine flu emerged in the early 2000s, but as far as we can tell, it hasn’t been around for a while. So, H3N2 vaccination is the key.

How good is the canine flu vaccine?

Well, it’s a flu vaccine. They’re not known for being incredibly effective, but are useful to reduce the incidence and severity of disease. I’m most motivated to have higher risk dogs (e.g. old dogs, dogs with other health problems) vaccinated to reduce the risk of them getting severe disease. It’s going to be less effective as a population control measure since it isn’t great for protection against viral shedding, but it should help some.

What dogs should be routinely vaccinated against flu?

That’s a tough call since it’s a really sporadic disease. You might not have flu within 100 km of your dog for its entire life, or you might run into an infected dog tomorrow.

My main considerations are risk of exposure and risk of severe disease.

  • Risk of exposure depends on whether the virus is in the area, how likely it is that it will be brought into the area (e.g. outbreaks nearby), how likely it is for the dog to be exposed somewhere else (e.g. the dog travels with its owner or goes to dog shows), how likely it is for the dog to be exposed to a high risk dog from somewhere else (e.g. contact with dogs imported from Asia, or dogs from other areas where flu is active) and how many dog contacts it has (the more contacts, the greater the risk, particularly if there are contacts with dogs of unknown health and travel status).
  • Risk of severe disease is the other consideration, as described above.  I’m quicker to recommend any respiratory disease vaccine in seniors, dogs with other illnesses and brachycephalics.

Thinking about those two components helps assess how useful the vaccine might be.

If flu is active in your area, vaccination is definitely worth talking about with your veterinarian.

How is canine flu vaccine given, and how often?

It’s an injectable vaccine.  It requires an initial dose and then a booster 2-4 weeks later. That booster is important and shouldn’t be missed. We don’t do that in people, but dogs need it since most don’t have pre-existing immunity from earlier exposure and vaccination. After that initial series, it’s boosted once a year.

Another potential issue is vaccine availability. It’s been a niche vaccine, but with the large number of outbreaks in the US at the moment, demand has outpaced supply. Shortages are currently an issue in many areas.

While not related to the vaccination theme of today’s post, the question of whether canine influenza poses a risk to people often comes up too.

As far as we know, currently circulating canine flu strains do not infect people. That doesn’t mean it’s impossible (the current H3N2 changed from a bird to canine flu virus) but there’s no evidence it’s a concern right now. The main concern is the potential for a recombination, where different flu viruses (e.g. human, avian, swine, canine) infect the same host and the same time, and then reassort and create a new flu virus. We don’t have evidence of this happening but it’s always a concern with flu viruses, and it’s why we try to limit the number of different flu viruses in circulation (in any species).

What am I doing about canine flu?

At this point, we don’t have any evidence of canine flu in Canada. It might occur any time, and who knows where it will pop up, but at this point, the risk of infected dogs in my area is low.

Beyond that, Ozzie and Merlin don’t’ have particularly busy social calendars. We live in the country and they don’t see other dogs here. They see a small number of family members’ dogs sporadically, but their overall dog contacts are limited.

Ozzie (pictured here) is young and probably at limited risk of severe disease.

Merlin’s 11 and has chronic lymphoid leukemia that we’ve been managing for a year. He’s pretty healthy, but presumably at higher risk of a complication.

If flu was in the area, I might vaccinate them, but their risk of exposure is still pretty low so I’m not sure I would. If they had more contacts, I’d vaccinate Merlin for sure, and probably Ozzie too. With no flu in the area and limited dog contacts, I’m not motivated to vaccinate them at the moment. For some dogs, though, vaccination is definitely worth considering.

And from a non-canine standpoint… get your own flu shot. It won’t protect you or your dog from canine flu, but it’s been a nasty human flu season, and it can definitely help with that.

How do I link all those? It’s not as big of a stretch as you might think, but it’s definitely getting into some theoretical components.

Dogs are unique from a Lyme disease perspective in that healthy individuals are very commonly tested.

Hundreds of thousands of dogs get tested every year for heartworm, and common heartworm tests also test for antibodies against Borrelia burgdorferi, the bacterium that causes Lyme disease. Seropositivity rates vary a lot by geography and lifestyle, but rates of up to 10% are not uncommon in some areas. The vast majority of those dogs don’t have Lyme disease. They were exposed to the bacterium at some point from an infected tick, mounted an immune response that produced detectable antibodies, and nothing untoward happened to the dog. A minority of exposed dogs ever go on to developing Lyme disease.

The upside: We get lots of surveillance data with all this routine testing.

The downside: There’s often a pressure to “do something” when there’s a positive result, even though doing nothing is usually the best approach.

I think things are improving, but a large number of healthy dogs are still treated unnecessarily with antibiotics (mainly doxycycline) because of positive routine antibody tests.

There are several concerns with that, but the potential for emergence of antibiotic resistance is one of the main ones.  Sometimes, people think that means a higher risk of resistance of Borrelia burgdorferi to antibiotics.  However, I’m concerned about emergence of resistance in the myriad other bacteria that are present in and on the dog, such as staphylococci and E. coli.

The risk of emergence of doxycycline resistance in Borrelia from unnecessary treatment of dogs is basically zero. It’s not because Borrelia can’t become resistant. Presumably it can, but it comes down to some basic ecology. There are a few basic things that need to occur for resistance to be an issue:

  • The bacterium has to be present.
  • A resistant strain has to emerge.
  • That resistant strain has to be spread to other individuals (directly or indirectly).

In dogs that are not actively infected (but still antibody-positive), resistance in Borrelia can’t emerge because the bacterium is not there.

In dogs that are actually actively infected, it’s theoretically possible that resistance could emerge during treatment. However, that would be the end of it because dogs are “dead end hosts” that don’t spread the bacterium any further. Emergence of resistance in reservoirs of the bacteria (in this case rodents, particularly white-footed mice) would be a concern, because then ticks could spread the resistant strain to many dogs (or people).

The main risk of emergence of doxycycline resistance in Borrelia burgdorferi is more likely heavy use of tetracycline in livestock, especially pigs.  Tetracycline is closely related to doxycycline, and the bacterial resistance mechanisms to the two drugs overlap. So, tetracycline exposure is a risk for emergence of doxycycline resistance, in general.

Livestock aren’t reservoirs for Borrelia, but heavy use of tetracycline on farms, especially in feed, could lead to exposure of mice to the antibiotic (when they get into stored or spilled feed, for example), and then theoretically there would be some resistance selection pressure if those mice are carrying Borrelia.

Does this happen?

I don’t know. I’m not sure it’s been investigated. Resistance doesn’t currently seem to be a big deal in Borrelia . However, it makes sense biologically.  While it’s not likely to cause a rapid increase in resistant Lyme disease, we worry about the longterm, cumulative impact of any antibiotic use, in any species (humans and animals). So, I wouldn’t discount it, and it’s yet another reason for us to try to minimize and optimize antimicrobial use in livestock and reduce environmental contamination with antimicrobials (from livestock and other sources).

Image from https://www.idexx.com/files/flex4-head-to-head-white-paper.pdf

As World Antimicrobial Awareness Week 2022 winds down, I’ll touch on a statement that I’ve seen a lot over the past week. “We need to reduce misuse and overuse of antibiotics” or “Misuse and overuse of antibiotics are driving antimicrobial resistance (AMR).” Those are great sound bites but largely miss the mark.

Yes, misuse and overuse are problems, but that’s only part of the story.  Focusing on misuse and overuse alone can lead to overly simplistic and ineffective approaches to combating AMR.

Anytime an antimicrobial is used in people, animals or plants, there’s some degree of selection pressure and risk of further dissemination of AMR.  It doesn’t matter if we consider it to be overuse, misuse or appropriate use. It’s what happens to the bacteria that are exposed to the drug that matters.

  • Misuse is important because there’s risk of selection for AMR with less clinical benefit.
  • The same applies for overuse: we create extra AMR risk without extra benefits.
  • But ANY use still potentially cause problems.

So, we have a problem with antimicrobial USE. Period. Misuse and overuse are part of that, but not the whole story.

Misuse and overuse are also sometimes subjective. We can say that antimicrobials shouldn’t be “misused,” but if we can’t clearly explain to prescribers and users what that means, we don’t achieve anything.

We absolutely need to reduce misuse and overuse. They contribute to resistance risk while providing little to no significant benefits.  For an issue like AMR, where there’s always risk, cost-benefit considerations are key.

But just as important is the need to IMPROVE use of ALL sorts. That often includes reducing use, but not always. It can involve changing things such as drug selection and duration or timing of treatment, to maximize the benefits and minimize the risks.

So, how to do we address antimicrobial “use” overall?

  • Pay attention to misuse and overuse, and try to eliminate those.
  • Better understand and communicate what constitutes “appropriate” use.
  • Develop robust surveillance systems so we can understand how antimicrobials are used, so we can know what’s actually happening and where we can intervene.

What’s as important, though, is reducing the need for any use at all by preventing infections before they start.

Antimicrobial resistance is an outcome of antimicrobial use, and antimicrobial use is an outcome of animal (and human) health issues. If we improve animal management systems, we improve animal health and we reduce the need for antimicrobials. That can include things like better raising of farm animals, vaccination, use of antimicrobial alternatives and improved access to veterinary care.  Improving public health and human healthcare likewise improves human health, and reduces the need for antimicrobials in people.

Healthy animals need fewer antibiotics.  The same is true for healthy people.

Improving health makes sense but gets less attention. There’s nothing sexy about it. It’s usually low-tech, and often involves improving use of routine measures such as maintaining water quality, sanitation, hygiene, ventilation and preventive medicine like vaccination. We’re not likely going to “tech” our way out of AMR. We’re going to improve things by using myriad basic health strategies to reduce our need for antimicrobials and preserve the efficacy of the ones we have.

I’m focusing on antimicrobials this week since it’s World Antimicrobial Awareness Week, but this is a timely topic and there’s an antimicrobial twist.

A couple of recent reports about a canine pneumovirus outbreak in a shelter in Tacoma WA and a separate outbreak of canine pneumovirus in a shelter in Las Vegas NV have, predictably, launched more concern about this virus (and some over-reaction).

The antimicrobial stewardship (or lack thereof) aspect is highlighted by a quote from shelter personnel in one of those reports: “We’re really treating it symptomatically by throwing antibiotics at it, that’s all we’ve essentially come up with.”

Throwing antibiotics at it.  For a viral outbreak.

Sometimes we need antibiotics during respiratory disease outbreaks to treat secondary bacterial infections in certain dogs, but antibiotics are massively overused in dogs with (often mild) upper respiratory tract infections, in both shelters and the community at large. Our ISCAID antimicrobial use guidelines for treatment of respiratory tract disease in dogs and cats are getting a bit dated (2017), but still highlight the considerations for antibiotic use in respiratory disease – and the overall limited need for such use.

Outbreaks like these are important reminders of the need for good routine infection control, prompt response to disease incidents, and effective communication.

They should also be a reminder to think about how we use antibiotics in respiratory disease in dogs and cats. I understand why antibiotics are “thrown” at outbreaks… they’re stressful situations, and there’s often pressure to just “DO SOMETHING!!!” However, from the standpoint of both effectiveness and antimicrobial stewardship (paraphrasing the immortal words of Winnie the Pooh), sometimes doing nothing is the best something.

Back to the pneumovirus outbreaks:

Since I’m lazy, I’ll cut-and-paste from a post about a canine pneumovirus outbreak in another shelter from earlier in the year, as not much has changed since then.

I always talk about pneumovirus when I list potential causes of infectious respiratory disease in dogs, but usually with the disclaimer “I don’t really know how important it is.” Studies that have looked at different dog populations have reported finding canine pneumovirus in 1-15% of dogs with respiratory disease, but most often in less than 5%. Rates of 0-6.1% have been reported in healthy dogs. Finding the virus in healthy dogs doesn’t mean it can’t cause disease, it just makes it harder to determine if it’s relevant in sick dogs.

Studies looking at antibodies against penumovirus in dogs (an indication of previous infection) have found high rates in healthy dogs, often over 50%. Dogs often develop antibodies to the virus after being admitted to a shelter. This suggests that this virus is circulating widely in the dog population and probably not causing much disease, or at least not much serious disease. When dogs mix in congregate settings like shelters, the risk of infection goes up.

My guess is that this virus does cause some disease, but likely usually just mild upper respiratory tract infections, with exposure being common when younger dogs start mixing. Once they’ve been infected, dogs are probably low risk for getting sick later in life. Shelters are high risk for exposure because of the number and variety of dogs in close quarters.  Dogs that haven’t been previously infected would be susceptible, and that could lead to an outbreak with what I’d expect to be relatively mild disease.

So, do these recent reports indicate that things are changing, since we’ve had a couple new reports of outbreaks in shelters?

Probably not. Most likely, this virus has been a cause of outbreaks like this before and we just couldn’t put a name to it. With advances in testing, we can identify things we missed before. Most likely, we’re just picking up the sporadic outbreaks of typically mild disease that pneumovirus has probably been causing for some time.

That doesn’t mean we should ignore it. We need to use good infection control practices to reduce disease and outbreaks in shelters. However, at the same time, we need to take care not to over-react to disease or to “new” things that might not actually be very new.

I’ve spent a lot of time in meetings listening to people debating whether to use the word “antibiotic” vs “antimicrobial.” I tend to stay out of those discussions because I don’t care too much either way.

  • Yes, they mean somewhat different things.
  • Yes, we want to be precise when writing guidance documents where the difference might be relevant.

However, 99% of the time, it doesn’t matter which term we use.  Their definitions are pretty variable depending on where you look, but commonly it’s something along the lines of:

  • Antimicrobials: substances that inhibit or kill microbes, including bacteria, viruses, fungi and protozoa (microscopic parasites).
  • Antibiotics:  substances that inhibit or kill bacteria.

So, antibiotics are a subset of antimicrobials. Most of the time, when we’re talking about use, resistance or stewardship, we’re focused on bacteria, and therefore antibiotics. However, it’s not all about bacteria, and some substances that inhibit bacteria also inhibit other types of microbes.

  • I tend to use antimicrobial when I’m writing scientifically.
  • I tend to use antibiotic and antimicrobial rather interchangeably otherwise.

Why not just use the “proper” term all the time?

  • Part of it is habit.
  • Part of it is a lack of motivation.
  • Part of it is using a term people are most likely to understand.

If you asked 100 people “What kind of drug do you usually get if you have a urinary tract infection?” I’d guess almost all would say “An antibiotic.”

If you asked 100 veterinarian or physicians “What kind of drug do you usually prescribe for a urinary tract infection?” I’d bet over 90% would also say ” An antibiotic.” Maybe even 100%.

That doesn’t mean we should avoid using the proper term when it’s important. If we’re working on international guidelines, we need to be absolutely clear what we’re talking about.  But beyond that…

TomAYto, tomAHto. PotAYto, PotAHto.

I don’t really care what we call them most of the time, I just want us to use them better.

As we start World Antimicrobial Awareness Week, I’m going to  try to write a few posts about various aspects of antimicrobial use and resistance in animals. This first post is a bit long, but it covers an important topic: antimicrobial use targets.

I get asked a lot about whether antimicrobial use targets are need in veterinary medicine. My typical answer is, “Yes, we need them, but we can’t set good targets – yet – in most situations.”

In Canada, we have no way to set proper targets because we don’t have enough good data on current antimicrobial use and efficacy, and we don’t know what targets would be useful. Targets need to be more than a political or marketing statement. If we were to say “Yay, we reduced antibiotic use in animals by X%,” but we have no idea if it was useful in terms of the animal health impact or reduction of antimicrobial resistance, so what?

In concept, antimicrobial use targets are simple: we set a level of use that we want to be below, at a national, sector (e.g. beef cattle), prescriber or farm level. However, it’s a lot more complicated than it appears.

  • Targets can be helpful, when they improve antimicrobial use, but “improve use” is poorly defined. It’s typically used synonymously with “reduce use” but they’re not always the same. How and when we use antimicrobials, how long we use them and which antimicrobials we choose are as, or more, important than the total amount.
  • Targets can also be bad, when they compromise animal health and welfare, and/or result in shifts in drug use that reduce the total amount of antimicrobials used, but actually worsen how and what antimicrobials used.

Most often, the focus of antimicrobial use targets is the total mass of drugs (kgs, tonnes) used. Why?

Total mass of drugs sold / prescribed / dispensed is usually the easiest number to get, and it’s often a big, scary number that gets attention. At the crudest level, it can be reporting of the total mass of antibiotics used in animals, overall. That’s pretty useless. We can get more information by looking at use in specific populations or animals.

My personal opinion is that mass-based metrics (the main way used to measure and set targets for antimicrobial use) largely suck. I use them, but that’s because it’s typically all we have, but they have major limitations.

What are some of the limitations of mass-based metrics for measuring antimicrobial use?

Mass just tells us how much antibiotic went into the whole animal population. It doesn’t tell us why, when or how.  Mass data of all antibiotics combined is particularly useless, because we use different dosages for different antibiotics, we treat different species differently, and there are large differences in sizes of different animals, from grams (e.g. chicks) to hundreds of kilograms (e.g. cattle).

Differences in drug potency also make it extremely difficult to interpret such a measure. For example, if I change from a drug that is dosed at 20 mg/kg twice a day to one that is dosed at 2 mg/kg once a day, I’ve reduced the mass of drug used by 95% (40 mg/kg/day to 2 mg/kg/day). That sounds great at first glance; however, it could actually be the last thing we want, since higher potency drugs (that are used at a lower dosage) are usually newer, broad spectrum, higher-tier drugs that are more important in human medicine as well. So, if a target was set to reduce antimicrobial use in Canada by 50%, we could do that quickly by switching to higher potency drugs, but it would actually increase the risk of emergence of serious antimicrobial resistance to more important drugs.

The table below shows an example of antimicobial use in dogs in two different scenarios. I took some of our published data about treatment of dogs for bacterial cystitis (Weese et al. JVIM 2021) and calculated the total antimicrobial use for 1000 dogs based on the study data, versus following the recommended ISCAID guidelines for antimicrobial treatment of dogs with cystits instead.

There’s a big difference in total antimicrobial use between the two scenarios, but the totally actually increases when the guidelines are followed! Why? Because use is shifted away from the newer, broad spectrum, higher-tier drugs that are dosed at lower mg/kg  than older drugs that are similarly effective. So, this change would probably be beneficial from a resistance standpoint, but would look terrible if we only focused on total drug mass used. I added a scenario at the bottom of the table where our intervention also dropped the treatment duration from 10 days to 5 days, to highlight how important duration of treatment is.  This should be a big focus for companion animal interventions since we still tend to use excessively long treatment courses.

Overall drug mass data can be useful if we’re comparing apples to apples, such as looking at year-to-year total kgs of antibiotics used in a certain species if the population hasn’t changed and if relative use of different drugs hasn’t changed. Mass-based measures of antimicrobial use have been used successfully to reduce use in livestock in Denmark, through their “Yellow Card” system. So, I don’t discount the utility of more refined mass-based approaches, but we can do better.  Overall mass of drugs used can be misleading in some situations, and doesn’t guide optimal stewardship activities. Ultimately, it’s a crude measure that can be hard to use outside of situations where there’s a very narrow and well defined scope of use.

There are additional metrics that can be used to provide more refined information, such as mg/PCU (population correction unit), defined daily dose (DDDvet), defined course dose (DCDvet) and animal daily dose (ADD). These all attempt to provide more context to the results, but each has its own limitations. They’re still better than just looking at total mass of drug, but even with these metrics we’re still left with a lot of gaps in understanding how antibiotics are used.

Ok, so I’ve whined enough about how mass-based metrics suck (or at least aren’t good enough). What can we do?

There’s not a single, one-size-fits-all measure that works best for all species, situations and goals, but we do have options. While everyone wants a single number on which to focus, that’s usually not be possible. We need to use combinations of metrics, including mass-based and dose-based metrics, and ideally also look more at how we use antibiotics and areas that are more amenable to action-based targets.  Here are some examples of things we could assess:

Percentage of animals treated

This can be a very practical and useful approach, looking at either an entire animal population or a more targeted subpopulation (e.g. a farm or production group). For example, we could look at the percentage of feedlot cattle that get antimicrobials for respiratory disease, or the percentage of dairy cattle that get antimicrobials for mastitis during a lactation. In companion animals we could look at things like the percentage of cats with lower urinary tract disease that get antimicrobials (which should be very low, because most don’t have infections), the percentage of dogs with acute diarrhea that get antibiotics (ditto) or the percentage of animals undergoing surgery that get peri-operative antimicrobials. This measure can tell us more about specific use and provide useful comparisons. If a feedlot treats 95% of their cattle for pneumonia, but a similar sized feedlot in the same province only treats 50% of their animals, that’s a relevant difference. If the farms are truly similar, it tells the farm treating 95% of cattle that they can likely reduce their use a lot through management changes or being more selective about which animals are treated (and they could look to the other farm for examples of what they could change). It’s directly actionable information that doesn’t necessarily aim to penalize the first farm, but can ideally spark some action.

Appropriateness of use

This is a big one for me. If we can measure how often antimicrobials are used appropriately (i.e. not just what and how much, but how they are used and, importantly, whether use fits with standard practices), we have a great metric to track. For example, knowing that 100 animals in a group were treated is somewhat useful, but knowing that 80 animals were treated according to guidelines and 20 were not tells me a lot more, and lets us focus our efforts on the situations where treatment wasn’t consistent with guidelines.

Who defines “appropriate” antimicrobial use and how that’s determined then become the big questions. Ideally, we’d look at what percentage of antimicrobial use follows accepted guidelines, but that only works if we have good guidelines. We have guidelines for use in some situations, but for others, so it’s not an instant fix.  We’ll never have guidelines that cover everything, but we should still strive to look at the appropriateness of use in common situations.

What do we need to have useful antimicrobial use targets of any sort?

  • A robust, accurate, secure and user-friendly data collection system that lets us efficiently measure antimicrobial use at the animal/veterinary/farm level
  • Political will to act (in Canada, our federated system means we require buy-in from all provinces, territories and the federal government)
  • Adequate and sustained funding
  • Effective targets that will actually have an impact on antimicrobial resistance (and not just another metric)

In the agriculture sector, we also need (well, maybe don’t actually need but really want) buy-in from industry groups. There will always be some hesitation to participate from groups that don’t want external interference or monitoring, but proper surveillance and targeting can be useful to them as well.  Ideally targets aren’t punitive, they’re informative. Knowing how a farm uses antimicrobials and how that compares to similar farms can be useful for assessing a farm’s practices. If one farm uses 50% more antibiotics than a similar farm, they need to think about why.

  • Are there management issues that can be improved so antimicrobials aren’t needed as often?
  • Are antimicrobials being used when they aren’t necessary due to misinformation or practices that simply need to be updated?

Having data can help figure out what’s happening, which can lead to action and ultimately improve production and save a lot of money on antimicrobials (and other veterinary costs). There will also likely be more scrutiny from consumers and trade partners about how antimicrobials are used. The goal of antimicrobial use targets doesn’t have to be restrictive. Yes, there could ultimately be an approach that penalizes people for being above the target level, but that’s not what targets are really about. They are meant to help us understand how we are using antimicrobials and identify ways to improve and monitor how we’re doing.

Back to the initial question: Do we need veterinary antimicrobial use targets?

  • Yes.

Can we set them now?

  • Not in Canada.

What do we need?

  • Development of a system to efficiently monitor antimicrobial use, and political will to put the time and effort into creating that system. Then we can think about how to use those data to improve things.

Dead raccoons have gotten a lot of attention in Toronto lately, for various reasons. Many urban areas have abundant raccoon populations, and whenever there are a lot of animals (especially of the same species) living in a relatively small area, there’s greater risk for disease outbreaks. A distemper outbreak is playing a role (maybe a big role) in the latest rash of dead raccoons being found across the Toronto area. That’s bad news for the raccoons, and unpleasant for the people who who find them, not to mention the overworked animal control agencies that get called to pick up the dead raccoons, while also trying to attend to sick and injured animals of all species.

Beyond the ick factor of finding these dead raccoons, there’s fear of infectious disease exposure, particularly for dogs, from raccoon carcasses and sick raccoons. (And let’s not forget about cats either… risks to cats usually get ignored in these situations).

What are the real disease risks from all these dead raccoons?

Overall, the risks are pretty limited.

Distemper in raccoons is caused by canine distemper virus (CDV), the virus that causes (unsurprisingly) distemper in dogs. Distemper can cause serious, including fatal, disease in dogs, just like it does in raccoons.

So are dogs at risk from sick and dead raccoons?

Yes, dogs can get distemper from raccoons, but the good news is that we have very effective vaccines against distemper in dogs. Distemper is included in the standard “core” vaccines that all dogs should get regularly. We typically start vaccinating puppies at 8 weeks of age and vaccinate them monthly until 16-20 weeks of age. At that point, we’re pretty confident they will be able to respond to the vaccine properly, so we normally then vaccinate a year later, then every 3 years. Distemper is extremely rare in properly vaccinated dogs. Even a dog that is overdue for vaccines is probably at very low risk of infection is they were properly vaccinated as a puppy.

How would a dog get distemper from a raccoon?

Most likely, it would occur when an unvaccinated (or under-vaccinated) dog has direct contact with an infected raccoon. Although the virus is excreted in respiratory secretions and feces which can contaminate the environemnt, most of the risk probably comes from direct contact with the animal. Survival of CDV in the envionment hasn’t been well studied in field situations, but it probably only survives for hours or at most a few days. If there’s sunlight, dry periods and temperature swings, that helps inactivate the virus faster. So while we can’t dismiss the risk from indirect contact, I’m mostly worried about a dog tangling directly with an infected raccoon, which happens commonly enough even when the raccoon isn’t sick or behaving abnormally.

What’s the risk from raccoon carcasses?

The risk of distemper exposure from raccoon carcasses is probably not much. While the carcasses are unsightly, any virus on the outside of the body would die fairly quickly. The longer the raccoon has been dead, the lower the risk, so delays removing dead raccoons create more ick than disease risk.

It’s still best to get dispose of carcasses (of any kind) as soon as is reasonable. Beyond distemper, there are other potential general infectious disease risks from carcasses, but overall the risk is low, and the risk of distemper transmission to dogs is very low.

That said, why tempt fate and have a dog potentially exposed to anything from a raccoon carcass? Regular readers will have seen various pictures of our new puppy, Ozzie. It’s looking like he’s (unfortunately) going to be one of those dogs that likes to roll in disgusting things. So, job #1 is keeping him from away from animal carcasses. If he did roll on a raccoon carcass, I’d be more concerned about the smell than a disease, but I’d still give him a bath (while trying not to contaminate myself in the process).

Raccoons with distemper can act strangely. Do we have to worry about rabies?

Yes and no. We’re always concerned about rabies. However, we don’t have raccoon variant rabies in Toronto (as far as we know). There’s pretty good surveillance in the region, and it seems not to have made its way to Toronto after its last incursion into Ontario in 2015, when raccoon rabies was focused a bit further west in the Hamilton area.  (In the last two years the only cases of raccoon rabies in Ontario were detected in skunks in the Niagara region.  Check out the interactive Ontario rabies case map for the latest surveillance and case info.)

At this point, the vast majority of abnormally-behaving raccoons in Toronto will have distemper. But, we can never completely dismiss the potential for rabies, either because raccoon rabies has sneaked into the city, or a raccoon was infected by another rabies virus strain (e.g. from a bat). Therefore, it’s important to keep people and animals away from raccoons – even those that look normal, but especially those that are acting strangely.

The take-home messages are pretty simple:

  • Keep pets under control and away from wildlife, being particularly strict with unvaccinated and under-vaccinated dogs.
  • Make sure dogs are vaccinated.

That’s about it. With some common sense and basic veterinary care, we can relax about the canine implications of distemper in raccoons.

Titres… ugh. I spend a lot of time answering questions about titres, with little data to go on.

What are titres?

Titres are a measure of antibody levels in the bloodstream. Antibodies are produced by the body in response to infection or vaccination.

What do titres tell us?

Titres indicate whether a specific antibody is present in the blood, and how much (or a relative idea of the amount of antibody that is present). No more, no less. It doesn’t mean that the antibodies are actually useful, or that the amount present is enough to prevent infection. It just tells us whether or not the specific antibodies we’re assessing are there.

What do titres not tell us?

Titres don’t tell us anything about other parts of the immune system, most importantly the components that make up what’s called “cell-mediated immunity.” I won’t get too far into the immunology here, but basically there are two main arms of the immune system, humoral immunity and cell-mediated immunity. Humoral immunity is driven by B cells (a type of white blood cell) that produce antibodies to specific antigens. Cell-mediated immunity is driven by the action of T cells (a different type of white blood cell) and does not involve antibodies. Both are very important for fighting infections, but measuring antibodies tells us nothing about cell-mediated immunity.

What is a “protective titre?”

By definition, a titre that is known to be high enough to protect against infection after exposure to a specific pathogen would be considered “protective.”  This can be determined through prospective studies following animals with known titres that are naturally exposed to the pathogen, or through experimental studies in which animals are exposed in a laboratory setting, and then watching/testing to see which animals still get sick or stay healthy. However, we don’t have much data about protective titres for disease in animals (and almost nothing that applies to field situations).

But labs report “cut-offs” for titres, so that’s the protective titre, right?

Here’s a statement from the 2022 AAHA Canine Vaccination Guidelines:

  • “…, at best, the determination of “protective titers” has been based on limited data. These data were thoroughly reviewed 20 years ago. Nothing more substantive has become available since then. ELISA-based in-clinic antibody detection tests have been available for CPV and CDV for more than 20 years. HI and VN tests, respectively, were used as “gold standards” to determine their sensitivity and specificity, as it relates to a “protective titer.” Commercial ELISAs have been applied in shelter populations outside of the laboratory and further compared with HI and VN tests. Such applications have provided no further basis for a determination of “protective titers,” primarily because the titers or amounts of antibody were not correlated with clinical outcomes. Recognizing these limitations, no values for “protective titers” are indicated in these guidelines, although some commercial laboratories will provide them.”

Some labs will report cut-offs, but it’s not clear from where those values came, and it’s exceedingly unlikely they are based on any study of protection from actual disease.

Here’s another statement from the 2022 AAHA Canine Vaccination Guidelines:

  • “Altogether, a titer, almost regardless of the amount, is not necessarily indicative of protection or susceptibility. Rather, it is more complicated than that. Disease in the individual animal results from the interaction of host, pathogen, and environmental cofactors. It can be misleading to forecast an outcome on the basis of one cofactor: a titer.

All that said, the presence of a detectable titre is probably a good sign and, in general, higher is better. However, what specific titres mean in terms of protection is impossible to say. No one should ever interpret a titre as indicating there’s no risk or no need to vaccinate. Similarly, a very low titre shouldn’t be interpreted as zero protection. We simply don’t know what those values mean.

Can titre testing be use lieu of vaccination?

This is the most common question about titres, and I’m not overly comfortable with it. It’s an appealing approach in some situations (although more costly that vaccinating). A high titre probably means good protection. A low titre might mean protection is poor, but it’s quite possible that the animal is still protected because there’s still sufficient antibodies and/or cell-mediated immunity (which we can’t measure directly). If there’s reason to consider stopping routine vaccination (e.g. adverse reactions, vaccine hesitancy), I focus less on titres and more on the animal’s vaccination history (i.e. number of previous doses and timing) and the animal’s ongoing risk of exposure. Rarely would a titre change what I’d recommend.

I’m required by law to have my pet vaccinated against rabies. Does a positive titre mean I can get an exemption?

No (or at least not anywhere that I know about). Rabies vaccination is required in many jurisdictions, including in Ontario for all dogs, cats and ferrets over 3 months of age. Sometimes exemptions can be made for pets that have a medical reason that vaccination should be avoided. However, that only exempts the pet from the legal requirement to be vaccinated, it doesn’t exempt it from the implications of a potential rabies exposure. If a dog or cat is exposed to a rabid animal, its vaccination status is a key determinant in what happens, ranging from a short observation period to 6 months strict quarantine (or even euthanasia). It doesn’t matter why the dog wasn’t vaccinated or if it has a high rabies antibody titre. A good titre would be some reassurance that the dog is likely protected, but it’s not enough of a guarantee to change the post-exposure management requirements.

There are specific titre tests for rabies that are required by some countries for importation of dogs. Those should be good, right?

“Good” in terms of accurate, with well-described, standard methods? Yes.

“Good” enough to prove that an animal has been vaccinated against rabies? Yes.

“Good” enough to show the animal is protected against rabies? Not necessarily.

While there is a standard cut-off for rabies titres for the purposes of international travel, it does not guarantee the animal is protected from  infection.  For good reasons, no one has done live animal studies looking at what titres protect dogs and cats from rabies virus infection. The 2022 AAHA Canine Vaccination Guidelines state “Antibody titer levels as correlates of protection have not been established for rabies, and serologic testing is not considered a substitute for vaccination.” So, rabies titres are best to prove that an animal has been vaccinated and provides a reasonable suspicion that they would be protected, but are far from a guarantee. That’s why we want to vaccinate whenever possible.

What is titre testing good for?

To me, titre testing is useful to say whether an animal has been vaccinated or has previously been infected. It’s probably of most use in a shelter situation where animals often come in with no vaccination history. If they have a titre, they have either been vaccinated or been previously infected (and are quite possibly immune to reinfection, at least for a while). That can be useful information for managing the animal (e.g. where to house it, whether to foster it, priority for vaccination, isolation approaches), particularly in situations where there’s an outbreak or high disease exposure risk.

There might also be value in testing dogs and cats whose last “core” vaccine was at 16 weeks of age. That’s the age where we assume they’ll respond to the vaccine, but some don’t. Personally, if in doubt, I’d rather just give another dose at 20 weeks (as per guidelines) but if there’s a reason to avoid vaccination, titres could be considered to see if there’s been a response to any of the earlier vaccines. I’d be looking at a yes/no versus a number, as with shelter admissions.

Beyond that, I’m less convinced and think the following series of questions provides more insight into immune status and the need for vaccination:

  • How old is your dog/cat?
  • With what has it been vaccinated and when?
  • What is your pet’s lifestyle, including exposure to other animals?

With those, I can have a pretty good idea about immune protection and disease risk, maybe as much (or more) than if I had a titre measurement.

I think this concludes our vaccination question series, but if there are other questions, send them my way, and we can move on to Part 6.

A busy hockey weekend delayed this topic. I thought this would be a quick one, but there are some interesting and complex issues…and as we move deeper into the vaccination series, there’s even less information on which to base decisions.

This post deals with issues surrounding vaccination at or near the time of surgery. Typically, we try not to load up on different procedures at the same time, but sometimes surgery may coincide with optimal timing for vaccination, or the time of surgery might be one of the few (or only) times an animal is seen by a veterinarian and thus the only opportunity to vaccinate (e.g. trap/neuter/release programs, barn cats).

When thinking about if/when/how to vaccinate, we need to consider a variety of factors, including impact on vaccine efficacy, risk of adverse events, ability to detect and manage adverse events, and practical components.

In humans, there’s no clear evidence that vaccination at the time of surgery is associated with a poorer vaccine response or increased risk of adverse events. An older review of the effects of anesthesia on vaccinationin children (Seibert et al. 2007) stated “We conclude that the immunomodulatory influence of anesthesia during elective surgery is both minor and transient (around 48 h) and that the current evidence does not provide any contraindication to the immunization of healthy children scheduled for elective surgery. However, respecting a minimal delay of 2 days (inactivated vaccines) or 14-21 days (live attenuated viral vaccines) between immunization and anesthesia may be useful to avoid the risk of misinterpretation of vaccine-driven adverse events as postoperative complications.”

The latter part of that statement is a common recommendation, i.e. avoiding vaccination close to the time of surgery to avoid situations where there’s a try to differentiate whether a fever or other non-specific issue is the result of a developing post-surgical complication (that might lead to something more serious and needs more investigation) or a common typically transient vaccine reaction (that might just need a dose or two of an anti-inflammatory). That’s relevant to veterinary procedures to some degree, but probably a lot less than in humans, since we don’t tend to recognize mild reactions like malaise as commonly or easily in our patients. It’s still something we have to consider if a patient has a surgery and a vaccine, and is a little bit off the next day… is something brewing, or is it just from the vaccine? However, I’d say those circumstances are pretty rare.

My take home message is that it’s probably better to space out surgery and vaccines if we can, but we don’t want to miss an important opportunity to vaccinate. If there’s concern that we might not see the animal again, I’d vaccinate (especially for an important vaccine that is needed asap). If the owner is committed to bringing the animal in later (e.g. we can vaccinate at the time of suture removal or shortly thereafter), then that’s probably ideal. However, we don’t want to let perfection to be the enemy of the good, so we should err on the side of making sure the vaccine gets administered, one way or the other.

So if we decide to vaccinate around the time of surgery, when do we do it?

  • Before surgery?
  • After the procedure but while still under anesthesia?
  • During anaesthetic recovery?
  • After the animal is awake but before the animal goes home?

Here are my thoughts:

Before surgery

  • Nope. The procedure is probably more important than the vaccine. We don’t want to risk having to abandon the procedure because of a vaccine reaction. There’s also the potential that any less serious reaction could impact response to anaesthesia, particularly blood pressure.

After the procedure while still under anesthesia

  • The pros are it’s easy to vaccinate an unconscious animal. We likely still have airway and IV access in the rare event that something really bad happens.
  • The cons are we can’t necessarily identify reactions as effectively if the animal is not fully awake.
  • I’ve seen some guidance on vaccination during anesthesia in humans that recommends avoiding vaccination under anesthesia apart from some select circumstances (e.g. certain developmental or behavioural disorders, or people with extreme anxiety or needle phobia). The analogy in the veterinary world would be an animal that is very difficult to handle and vaccinate, and the risks to the animal and handlers from vaccination while the animal is conscious outweigh any minor concerns about vaccination during anesthesia (e.g. vaccination of feral cats).

During anaesthetic recovery

  • There’s a lot of overlap between this option and vaccinating while the animal is still fully anesthetized (see above). We still hopefully have IV access (but not necessarily, depending on the clinic and procedure), so it’s easier to manage a serious complication. However, anesthetic recovery is already a complex time physiologically and it might be harder to identify early signs of an adverse reaction.

After the animal is awake but before the animal goes home

  • The pros are the animal has recovered from anesthesia and is getting back to normal physiologically, and we have a better ability to detect any complications that develop. The cons are the animals has to be handled more and poked after going through a procedure. Those concerns are minor for most animals, but the additional downside (which may be the main issue) is probably logistics and the risk of forgetting to give the vaccine.

Considering all these factors, it probably makes the most sense to vaccinate after anesthetic recovery, as long as the animal can be safely handled. Ideally that’s well after anesthetic recovery, but not as the patient’s walking out the door, so there’s a bit of time to observe the animal after vaccination. If the animal is getting an anesthetic in the morning, and is going home in the evening, vaccination an hour or two before discharge might be the sweet spot.

Like a lot of issues pertaining to vaccination, our decisions should be based on consideration of costs and benefits, but are complicated by the fact that we have almost no hard data on those costs and benefits. Some common sense can guide us; while I think my comments above are pretty reasonable, they are undeniably light on evidence.