Hello, everyone, and thank you for joining us today. My name is Doctor Nova Schiller and I'm the veterinary medical advisor at BioGal Labs. Biogal is the manufacturer of VaccineCheck, an in-house titer test for core vaccines in dogs and cats.
It is my pleasure to introduce our speaker today, Doctor Richard Ford. A bit about Doctor Ford, a graduate of the Ohio State University, Doctor Ford practised small animal and equine medicine prior to completing the internal medicine residency at Michigan State University. Subsequently, he taught internal medicine at Purdue University for 4 years, after which he joined the medicine faculty at North Carolina State University.
Doctor Ford was also the lead editor of the 2017 Aha canine vaccination guidelines and has served as a co-author on the AAF. Feline vaccination guidelines. He currently coordinates the Rabies Awareness Initiative in the US and the rabiesAware.org website, a resource in the US for veterinarians on state laws and regulations governing rabies and rabies vaccination.
Outside of veterinary medicine, Dr. Ford spent 28 years with the US Air Force as a biomedical scientist. He retired from the USAF Reserve as a brigadier General, where he was assigned to the office of the Air Force Surgeon General at the Pentagon.
Now, before we begin, if anybody has any questions during the webinar, please, please feel free to write them, but to write them in the Q&A box and not in the chat box, and we will be doing a Q&A session at the end. So again, thank you so much, Doctor Ford, for joining us today, and I will pass it on to you now. Well, thank you, Noga.
I really appreciate the invitation. And a special thanks to all of you who have, signed into this. You're gonna have to excuse me, I'm recovering from kennel cough, and, but I think we can get through this, all right today.
The point I wanted to make before we actually start is the fact that this is a new presentation. And I've developed this in order to communicate some of these really key issues regarding the role of serology in clinical practise. And I think from my perspective, this is a very underutilised resource in veterinary medicine.
So as we go through this, I hope to stimulate your interest and hopefully, we'll have time for a few questions at the end. I might add that I have written a manuscript pertaining to this lecture, and as we were discussing earlier, we're going to make that available on the BioGal website, so you should have access to that in the very near future. Now, with this slide, what I wanted to do was kind of review immunology, everything you learned in veterinary school on one slide.
If you look at this image, the green viruses are attacking the patient. Through a series of steps, activated B lymphocytes are released, and they subsequently release antibody which binds to the pathogenic virus and neutralises the infection and protects the patient. But as you know, there's, in addition to B cells, there are T cells.
So we're dealing here with humeral immunity, the B cells, and cell-mediated immunity, the T cells. But with both B cells and T cells, there are, This phenomenon called memory. And memory is a subset of lymphocytes that live in the germinal centres of lymph nodes and have this incredible ability to recognise and remember.
A particular antigen, even in the absence of antibody. And this is what provides really long-term protection. The point here is that we can't measure memory, B cell or T cell.
We can measure cell-mediated immunity, but it is very complex and extremely laboratory-centered. So what we're talking about is Antibody, something we can easily and inexpensively measure. The point of this lecture is to talk about some of the issues concerning the application and indications for using antibody testing in clinical practise.
Now, antibody testing in food-animal medicine has been around for a long time, and I use as an example, these commercial flocks of birds in which they have literally millions of birds in the population at risk. In order to monitor the population health and do surveillance for infectious disease. The managers will actually take 5 or 6 birds from each of the designated pens each week.
They'll kill the bird and test those for antibody to as many as 10 or 12 different viruses and bacteria. And as they do this, they'll get a little background noise, monitoring the flock on a weekly basis. But, All of a sudden, in one pen, there's a red flag.
There's a, a group of birds that have a high level of antibody to one pathogen, indicating that the flock, at least that pen, is infected. They use this and in some cases, depending on the pathogen. They may kill all of the birds in that area to save the population at risk.
So, antibody testing from a herd health perspective has really been around for several years. But something happened, and it happened in the early 2000s when we began to write vaccination guidelines for the dog and the cat. And for those of you who were practising at that time, you may remember the fact that we recommended extended booster intervals for the core vaccines, distemper, parvo and adeno, Panluke, herpes, and calici.
That recommendation created incredible controversy. Most veterinarians had been given annual vaccines and continued to do so despite the recommendations. And the issue of should we use a three-year interval or not remained very controversial, actually for quite some time.
Now, what's interesting, this actually was a key driving point in the role of applying or using antibody testing in practise in individual patients. And what did that is veterinarians who are saying, you know, I really don't trust your 3-year interval thing. So, I'm going to do antibody testing to verify that parvovirus and distemper virus actually immunise these patients for more than one year.
Concurrent with that was an interesting phenomenon in human medicine. And if you recall, in 1998, a physician, Doctor Andrew Wakefield, published a report, this was not a research paper. Detailing the fact that in 6 children.
He assumed or presumed that measles vaccine resulted in autism spectrum disorder. That literally became the shot heard around the world. As you know, parents quit vaccinating their children for measles, and subsequently, measles outbreaks surfaced in multiple locations around the world.
And interestingly, they continue today. In South Carolina, in the United States, They've just yesterday confirmed 1000 people with measles, mostly children, over 90% of whom were never vaccinated. So, it is a very real phenomenon.
But the spin-off from vaccine hesitancy in human medicine is clearly impacting veterinary medicine. This interestingly became a key driver for Clients of dogs and cats were requesting that a veterinarian perform antibody testing rather than routine vaccination. It was an interesting phenomenon to see that.
So, Now, veterinarians are submitting blood for titers, for individual patients, not the herd, but they wanna know what is the antibody titer in that cat. Now, what's interesting. Is that, as I've looked at this for some years now, I find that the profession has really been kind of the doubting Thomas on all of this.
There's been a lot of hesitancy on the part of our profession regarding the adoption of antibody testing. And there are 3 key questions that I've surmised result in this perspective. And one is an antibody test really a valid indicator of protection or protective immunity?
Important question. Secondly, why would I test? What are the indications for testing in clinical practise?
Is this a reasonable thing to do? And 3rd, if I do test, And I get a positive versus a negative result, how does that test result get interpreted to the point that it impacts individual patient management? This is what we're gonna talk about.
This is kind of the primer on antibody testing and practise, and we'll centre around these questions. First of all, I wanna be very clear. With what we know today, and this is in contrast to what I was taught, but what we know today is that a positive antibody test result is in fact a valid indicator of protective immunity.
So it gives the clinician objective information. For some But not all vaccine preventable disease, and that's important to recognise. When you talk about antibody testing, or it's critical to, I think, understand there are two fundamental or basic categories of antibody testing platforms.
One is quantitative testing. This is a laboratory-based reference standard. The other one is qualitative, or in this case of the vaccine check test kit, semi-quantitative testing.
The differences are this, when you're doing a quantitative test, you're sending serum or blood to a laboratory to get a number, a specific number that represents the dilution of antibody that neutralises virus in an in vitro system. This is an end-point test, and it is only laboratory-based. You're not doing titers in practise, per se.
Now, this was interesting. I've looked at several reports from commercial laboratories, and the results would come back posted 1 to 1600, for example, for parvovirus, positive. What I have found is this interpretation or reporting has caused confusion among the clinicians, in that they've interpreted, quote, positive in a couple of different ways.
One indicating that, gosh, the patient actually has parvovirus as, and is infected. But I wanted to emphasise that laboratories do not make a diagnosis. They report the results as positive or negative with a tighter.
In, on the basis of a, you're exceeding or at the standard laboratory reference value for that laboratory. And this is not necessarily something that would apply to other laboratories. So these tests are actually unique to the individual laboratory.
It takes days, usually 2 to 3 days at least, to get the results back. On the other hand, and this is where the technology has really improved, the qualitative, semi-quantitative testing platforms give you truly a, a yes, positive, or no negative, which is all the clinician needs. It is not relevant to know the amplitude of the titer since that doesn't reflect the degree of immunity.
You're either immune or you're not. These are in-clinic or point of care test kits, and interestingly, the results are available in minutes, and they are available at a significantly lower cost than a commercial laboratory, at least in the United States. I've queried several of these laboratories, and the prices are very varied from $200 to as much as $400 for a simple antibody titer.
So, there's an opportunity cost-wise with today, what's equivalent information. Now, this is the take-home message. Today, using either the quantitative or qualitative testing platforms, there is exceptional correlation between a positive test result and protective immunity for canine distemper, parvovirus, adenovirus, and feline parvovirus.
That's the key message, and we're going to centre around those four viruses. There are 2 test kits available in the United States, the vaccineCheck, which is now available in multiple countries, and a test called the tier check. It was an older test purchased by Pfizer Animal Health, now called Zoatis, in the day.
The VacineCheck test kit is a much newer, easier technology to perform, and it offers testing for distemper, parvo, and adenovirus. It also, they have another test kit for feline Panluke, herpes virus, and calici. I put herpes and calicivirus in parentheses because there is not good correlation between antibody and protective immunity because of the role of cell-mediated immunity in protecting cats against these infections.
So we're really focused on the 43 canine panluke for the cat. Results in less than 25 minutes. So it could be done with a client still in the practise.
The cost, I just verified this, at least in US dollars, is somewhere around $30 a little bit less. The Tighter check test kit is an older and somewhat more cumbersome technology. It's been around for several years, but it does require man, managing and maintaining a group of solutions to perform the test.
It really lends itself well to batch testing, but the VxiCheck test kit, It lends itself well to either individual patient testing or batches of tests. I wanted to show you, a little example of what I use when I'm teaching this, in that, I think it's relevant to everybody who's considering, antibody testing in practise to grasp this concept. What does a positive antibody test result mean?
Remember, this is different than an antigen test. We're talking about antibody, and there are variations to that, and I use the acronym PII. I think this is.
A way of helping you to remember how to interpret these results. You know, and I know that there are lots of antibody tests available commercially and through test kits, and it's important to understand what a positive test result means. And it can mean one of three things.
It can mean either the patient is protected. Or it can mean the patient isn't protected, but is actually infected. And on some instances, it can mean the patient is exposed to a particular pathogen.
Now, we've already established the fact that for distemper, parvo, adenovirus, and feline panluke, a positive antibody test correlates. Exceptionally well with protection. It gives you and the client objective information about the immune status of that patient for those diseases.
Now What about infected? Can you think of particular diseases for which a positive antibody test is used to diagnose infection? I think the obvious one is leptospirosis.
A lepto antibody titer is not a correlate of protection, but it is used to confirm infection. Lyme disease, if you're doing that using the C6 peptides as the target antigen, antibody to that correlates exceptionally well with a patient that is infected with Borrelia bergdorferi. It's a very good correlation on that, if using the C6 peptide as the target antigen.
FIV cats that have FIV immunodeficiency virus antibody have a positive Antibody test, they are infected. They are not protected, and they have not, it is not just a measure of exposure. Now, there are antibody tests that if positive, only reflect The fact that the patient has been exposed, not infected nor protected, and Ehrlichia and anaplasma are classic examples.
Following exposure, these animals, dogs can maintain Ehrlichia antibody for months, if not longer, following exposure, yet never manifest clinical disease. In addition, toxoplasmosis, antibody to the canine influenza viruses, which we've seen in the past in the US, pretty rare today, but we were one time, and you can purchase antibody to that. By the time the antibody develops, the virus.
Has already stopped. It is, the viremia has ended. It's a very short-lived infection, but the antibody lives on.
So CIV antibody only really means in the patient has been expected. In this context, there is one more. Everybody watching this has to know this.
I think it's really important to know one more disease or pathogen produces antibody that only is interpreted as exposure, not infection, not protection. And that is rabies. Internationally, That a rabies antibody titer is not a legal index of of protection.
Certainly doesn't reflect infection, but it only means the patient has been exposed, if you will, to the vaccine, and it's used in the form of titers to verify or validate that the patient has met vaccination requirements, depending on the country. But it is not a legal. Representation of protection.
Now, with regard to antibody testing, what I'd like to do is kind of walk through some of the testing indications and how to interpret the test result, given the indication. What do you do if it's positive? What do you do if it's negative?
And I've gone into quite a bit of detail in this, in the manuscript that will be posted for you if you're interested in looking at that. But And you don't have to write this down, but I wanted to show you, these are the Some recommended indications. Now, this is my list, based on my experience and that of other veterinarians who are actually using antibody testing in their practise.
I've looked at this for, for about 67 years now. Now, most of these at the top of the list, to verify post-vaccination immunity, there are several, Categories under that, that I think have relevance for some, maybe not all, but for certainly for some dogs and cats. For example, those being bred for resale.
Certainly, pups and kittens being sold are frequently taken to shows where there's a lot of exposure. It would be nice to know what their vaccination or immunisation status is prior to being exposed to a lot of other dogs. Canine competitions.
I had no idea how much went on in this category. I'll show you some pictures. And certainly dog parks, daycare facilities.
For young dogs, in particular, maybe not for all dogs, but for young dogs participating or frequenting dog parks and being left in daycare facilities, knowing that the dog. Has been vaccinated and is immune is an option or an opportunity to provide objective information to the owner that, yeah, your dog's protected against these core diseases. Then there's the issue of the non-responder.
I'll show you some pictures of that. Dogs, cats, presented to the practise with an incomplete or no history of prior vaccination, you can at least assess their immune status with a simple and quick antibody test. There are other medical reasons which are listed below there, vaccine adverse reactions, the vaccine hesitant client, Immune-mediated diseases, chronic illness, and I'll go through with a few examples of each of those.
I think all of you are familiar with the basic juvenile vaccination series for the dog and the cat. This is an example of the dog. We've published this in the guidelines, both the BSAVA in Britain and the The American Animal Hospital Association guidelines in the US all are saying the same thing.
We recommend 3 doses of C. Vaccine. Now, the issue with the juvenile dog and cat is the purple curve.
That purple curve represents maternal antibody. And we know, and I think all of us do, that if you attempt to vaccinate in the presence of maternal antibody, Immunity doesn't occur. Maternal antibody is profoundly capable of interfering with vaccine.
Now, the argument is, we don't know what the magnitude or amplitude or the slope of that purple curve is in every patient, and it does vary, even within a litter, it can vary quite substantially. But what we do know today, and at least in a pretty large study done by the University of Wisconsin, In the United States, it's estimated today that about 50% of the dogs vaccinated at 3 months of age, 12 weeks. Still have sufficient.
Maternal antibody to interfere against Parvo. And distemper, about 50% of the dogs vaccinated, at least in the US, Do not enjoy immunity to parvo and distemper, which puts emphasis on that last dose, the 16 week dose when maternal antibody is at its lowest ebb, is the dose in most cases most likely to immunise against these core diseases. But in that University of Wisconsin study, it was noted that up to about 15% of dogs, even at 16 weeks of age, were not immunised against distemper and parvo, leaving us to wonder just how big of an issue can this be in the clinical setting.
We assume that maternal antibody has waned to negligible amounts by 16 weeks, but it appears today that that is not the case, and there are actually reasons for that. But the bottom line is, In order to verify that a dog, that is, for example, a valuable dog that will be attending dog shows, or a pet that will be going to daycare, or dog parks. Knowing that they're immune can be established by testing them for antibody.
2 to 4 weeks following the last dose administered in the initial series, and that gives you a very objective picture of their immune response to the core vaccines. If, in fact, they are negative, it is essential that they be re-vaccinated immediately. So, that's a good management tool from that standpoint.
And again, not for every client, perhaps, but I think for those that do. See potential for risk or for congregate activities that there may be value in recommending that. This surprised me.
I've never been, Much into the dog sale business, but there are websites that provide a little bit of insight on how large the dog sales market really is. And as I did a little background search on that, it surprised me that in Europe, online sales annually are about €1.3 billion.
In the United States, dog sales are $4 billion annually. This is big business. And if there's that much value attached to selling dogs, Understanding or knowledge that this dog is in fact Immune to the core diseases, these critical diseases, is value-added.
So there's an opportunity, I think, and we do recommend that for dogs that are being presented for sale. And of course, congregate activities, the dog parks. Obviously, antibody testing for every dog going to a dog park is probably not practical or even necessary.
But for the young dog, recently vaccinated, under a year of age, that will be attending dog parks or daycare facilities regularly, there is, I think, a level of confidence that can be gained for the clinician, as well as the owner, knowing that the dog. Has protective immunity, or in the case of the cat, panleukopenia, not that you see a lot of cats in dog parks, but I do see a lot of young dogs, pups in dog parks, probably, some of which shouldn't even be there. My favourite Oh, I guess it's my favourite liability for dogs is the community water bowl you see on the right.
What a perfect way to spread disease. But they're everywhere. They're outside retail stores, they're in dog parks.
So, this is another reason. Knowing that the patient is objectively immune provides that level of comfort, confidence that you're OK to participate. Kenneloff may be an exception there.
This surprised me. I had no idea the magnitude to which dogs engaged in competitive sports globally. Now, I did research on this too, not that this has any continuing education value whatsoever, but I wanted you to see this.
I found 78 different categories of sports that dogs compete in. In those 78 categories, there are over 50 different specific competitions. Have you heard of these?
Some of you may have tribal or urban herding, very popular in Germany. It's kind of dog soccer, I guess, with a great big soccer ball. Then there's, if I pronounce this correctly, bike joking, or canro, or bike skiing.
In which a dog is attached to a human, and they compete on bikes, or skis, or just cross-country running. I had no idea those kinds of competitions took place. And then, of course, this dog competitions, very popular around the world, very impressive, but it's, it's an aggregate community thing, and if your dog is going to participate in those kinds of activities, It might be reasonable to assure the client that their dog is immunised.
And in the United States, I don't know how prominent this is outside the US. We have puppy bowl competitions, and I can't help but wonder how many of those puppies have finished their juvenile series of vaccines. And then this one.
You tell me if I don't even think I can pronounce that correct, Shepherd's shimozel. This is a New Zealand thing. It's an annual, huge event where hundreds and hundreds of dogs get together and compete on an obstacle course with their owner.
I just wanted to make sure that you knew that. Now, aside from the social activities and risk for exposure and potential application of antibody testing, there are some more medically-centric reasons. And this one is pretty significant.
For those of you who were practising in the 1980s, That's when we really discovered parvo virus, and the first vaccines were released in the mid-1980s. But during that time, veterinarians very quickly realised that there were some dogs, certain breeds, Dobermans and Rottweilers, that despite being well vaccinated, were not immunised, and they got parvo. And we attributed this to maternal antibody in the day, but it turns out that it has nothing to do with maternal antibody.
These dogs actually have a genetic defect in which they fail to express the epitopes on the antigen presenting cells. In effect, when they see a parvovirus vaccine, they don't see it. They don't process it.
They don't make antibody. So, these are now deemed the genetic non-responder. And the emphasis point here is these dogs are recognised globally.
These dogs are not unique to Dobermans and Rottweilers. We identified 22 genetic non-responders in one practise in California a couple of years ago. In a 3-month period.
So they are out there. We actually have anecdotal reports suggesting that the American Pit bull Terrier is one of the dog breeds, if you call that a breed, but one of the breeds that is susceptible to being a genetic non-responder. At least there are lineages of those, within the pit bull breed.
What's interesting, there are international estimates that 1 in 1000 dogs are parvovirus non-responders. You cannot force immunity by giving them more vaccine. They can't process the antigen.
And interestingly, it is estimated that 1 in 5000 dogs are Non-responders to distemper. So, it is interesting, they are out there. The only way to identify the non-responder is to test them for antibody 2 to 4 weeks after completion of the juvenile series.
Something to consider, particularly in somebody's dog who is particularly valuable. Another area of indication is in the vaccine adverse reactions category. This is in the United States, probably fairly poorly addressed.
In the UK and Canada, they actually do a much better job of documenting suspected adverse reactions to vaccination. So, I've collected a list, this is my list of adverse events that occur associated with vaccination. This probably isn't comprehensive, but it is documented.
Each of these are, are pretty well identified and described in the literature. So, it does occur. But what I wanted to emphasise is that in a very, very large study done by George Moore out of Purdue University, looking at almost 6 million dogs and 250,000 cats.
The estimated incidence of adverse reactions to vaccines is about 0.1%. So, they don't occur very often, but they do occur, and they usually occur in the young dog, 1 year of age and younger, most often, although they can occur at any age.
They occur in small breeds. Dogs under 10 kilogrammes, 22 pounds, seem to be at greater risk, particularly dogs receiving multiple doses of vaccine at the same appointment. And a good example is this.
I think most of us on the webinar today have seen this. This is angioedema. It is an acute type one hypersensitivity, literally, local anaphylaxis.
So, this is a generally pretty benign procedure, consequence of vaccination, generally attributed to The culture medium used in developing the vaccine, bovine serum albumin. And this kind of reaction does occur, it occurs acutely, and in the process of treating these patients, it's not unusual to give corticosteroids. The question always comes up, if I give corticosteroids to a patient that I've just given a vaccine to, what does the steroid dose do to the immune response associated with the vaccine?
I want to be very clear on this. It does essentially nothing. Antibody responses, B cell responses are not impacted adversely by doses of corticosteroid.
Cell-mediated immunity is. Big misconception in human and veterinary medicine, that corticosteroids compromise the immune response to a vaccine. I will tell you, I've reviewed this in the emergency department literature just recently.
Of all of the papers and the guidelines for treating post-vaccinal angioedema in children. They all give corticosteroids. They will give children epinephrine because of the tendency for laryngeal edoema.
But the point I wanted to make with this slide is that, if this patient, and they usually do, survives, and comes back for another dose of vaccine, is there a risk that re-vaccinating the patient will exacerbate an adverse event? Well, the option as an alternative is to test them and determine whether or not they have antibody. If they do have antibody, there's no need to administer vaccine.
It gives you that option. It gets a little more complicated if they don't have an antibody response, and they are deemed as a pup or a kitten susceptible. So, then the option of giving a vaccine may be necessary to pre-treat with corticosteroid, or more likely, an antihistamine.
I mentioned earlier, the issue of vaccine hesitancy among veterinary clientele. It is Seemingly becoming a significant issue, big enough that it is actually impacting national vaccine sales, at least in the United States. Now, there's a lot of people who are concerned, and their concerns are pretty standard, you're over-vaccinating my dog, vaccines don't work in dogs.
Vaccines cause injury, vaccines are unnecessary. These are kind of the concerns expressed. There's one rather large survey recently published in the US that pointed out that of the dog owners they consulted or surveyed, half of them support one of these concerns.
I find that kind of interesting. So there's, there's a lot of concern out there. And for the truly hesitant client that just doesn't want their dog vaccinated.
The option or an alternative, rather than just say, get over it, get the vaccine, which is not what people want to hear, you can at least offer them the option of doing antibody testing to see if they even need to be vaccinated. This, however, raises the question. If a dog is Vaccinated and has a positive antibody test today, will that test be positive tomorrow?
So does a positive test today look forward? And in a sense, it really does. Let me share with you a quick story.
On immune boosting. Now, every Christmas, my sister-in-law sends me a bottle of stuff like this. She thinks I need my immunity boosted, so I have a freezer full of immune boosting pills.
I looked into this to try to discover what this stuff really is. And in my research, quote unquote, I discovered a very interesting article, medical published publication, that interviewed the general public on what they considered to be an immune boost, what boosts your immunity the most, and they ranked them from high to low, 1 to 28. And at the top of the list, diet was the most significant immune boosting thing along with fruit.
Vitamin C, antioxidants, and then down at the bottom of the list, between soups and honey is the only one thing on that list that's really known to boost immunity, vaccines. Why would I vaccinate my dog when I can just give him some chicken soup. So you can see the perspective of the general public on where vaccines fall into the category of immune boosting.
But let me share with you a couple of things that you probably didn't get in veterinary school. Question to all of you, what is a boost? There is an immunologic definition of a boost.
And it is a fourfold or greater increase in the antibody titer following administration of a vaccine. That is a boost. If it's less than a fourfold increase, that is not a boost.
So, given that, I have found there are 3 major misconceptions regarding antibody. Boosting in veterinary medicine, at least. And one of them is that the higher the antibody, the tighter the greater the immunity.
And that's not true. You're either immune or you're not. So, when testing for antibody, a tighter number, and numerical value isn't essential.
You just need to know if they've exceeded the threshold for that particular test or not. So, that is incorrect. The second misconception is that when I get boosters, and we do this all the time, you're actually boosting antibody.
You're actually raising the titer by 4-fold or greater. Are you? Let me show you what actually happens, and this is relevant in real life.
In this graph, tier is on the up and down axis and age on the horizontal axis, and I'm gonna add in here the threshold for immunity. So, to be protected, the antibody titer has to exceed that threshold. Now, in the young juvenile dog or cat, you're going to give 3 doses, presumptively, of the initial core vaccines.
One of those, most likely the 3rd 1, will immunise the dog or the cat, and the antibody response to distemper parvo adeno and feline parvo panleukopenia very much looks like this. Now, it will vary from dog to dog, cat to cat, but the bottom line is you get a profound, lasting response in most. Not all, about 15%, don't enjoy this level of immunity following the juvenile series, which is why we give a booster one year later.
Now, for most dogs and cats, when you do that booster, the existing antibody interferes with the boosting. Just in the same way, maternal antibody interferes with the vaccine. So, you can see that you're doing that one-year booster after the primary series to really target those Percentage of animals, dogs and cats that didn't respond as well to initially to the vaccination, in the juvenile series.
So we tell the patient, conventionally, return in 3 years for another booster. But interestingly, the dog or the cat is now 4 years and a few months old, and there's still sufficient antibody there that boosting, in most cases, is not likely to happen because of interfering levels of existing antibody. Antibody does last a long time.
For the core, at least for the core vaccines. Now, 3 years later, they come back, antibody, like any other protein, will degrade over time. And as a result of that, When you do administer a booster.
Say 6 years later, That booster in the presence of low levels of antibody does, in fact, boost the antibody level. So that may be the first boost that actually occurs. We don't know that every dog, every cat will be somewhat different.
But the bottom line is, this is a pretty good general perspective of the population at large. Now the issue that this raises, if you can see my cursor is what happens when the antibody level falls below the threshold. Is the patient susceptible?
That's the third misconception. And now we say, gee whiz, he's vulnerable. But is he?
So, in this span of time, when the antibody level wanes below the protective threshold, Interestingly, and you know this, we don't see distemper in adult dogs. We don't see parvo in adult dogs or Panluke in adult cats. So, the bottom line is, What is doing this?
And the fact is that a low or negative antibody titer doesn't necessarily mean susceptible. It does in the juvenile patient, but it doesn't in the adult, if they've been previously vaccinated because they have memory. And it's that memory that serves to protect us and animals if they've been previously vaccinated.
So, you can see the perspective, and you can see how doing antibody titers or antibody level testing qualitatively or quantitatively can bring some value in knowing where the patient is in the scheme of things over time. The patient that has been previously treated for immune-mediated disease, particularly, we're talking about hemolytic anaemia or immune-mediated thrombocytopenia. All of the vaccine recommendations generally recommend not vaccinating these patients that have recovered from IMHA or thrombocytopenia using a modified live vaccine.
The issue is that administering a modified live vaccine versus a killed vaccine may actually provoke the immune response sufficiently to reactivate the disease. This isn't known, this isn't well-documented, but it is hypothetical among immunologists. So, it's a reasonable concern that if a patient that has recovered from IMHA or IMT that in fact, Rather than administer a booster dose, the alternative is to measure the antibody, and in all likelihood, that patient will have a positive antibody test, giving the clinician and the client comfort knowing the dog is protected now and has.
Memory that will probably last for Many years. Assessment of the patient with chronic illness. Now you and I know that from across the room, you can tell this patient is drinking a lot of water.
Now, chronic illness is a real unknown with regard to vaccine. What happens immunologically when you vaccinate? Do you, does the patient even respond if he's hyperadrenal corticism, chronic kidney disease, cancer, cancer, chemotherapy?
Are they able to respond? And I think another question in this equation is, could vaccination in some way compromise the patient with chronic illness? And that's an important issue as well.
So, the point I'm making here is that by testing for antibody, You can make that decision as to whether or not vaccination is even necessary in the patient. Objective information can quickly be provided in these subsets of patients. A question that I get, actually quite often, is, when do I stop vaccinations?
We all know when to start them. We've all published these in feline and canine guidelines. The starting point of vaccination is very clear.
Less clear is when to quit. And we get this question, I do, from veterinarians in practise, as well as from clients, is how long do I have to give these? For something like rabies, where rabies vaccine is required, by law, it must be given at the appropriate interval throughout life.
But what about the core vaccines, distemper, parvoadal, Panluke? It is reasonable around. 1011 years of age to test for antibody.
If these dogs or cats have a positive antibody test, they will be immune for quite some time. And I think it's reasonable, they'll be immune the rest of their lives, and it's feasible to discontinue, given the objective information you've gained from the antibody level, to discontinue the routine. Triennial boosters.
And the last example that I have, we've looked at this quite a bit, and this is more of a population management issue for shelter house dogs. There's been a couple of papers published that suggest that in shelter house dogs, I don't have that information on cats, but in shelter house dogs, up to 50% of dogs entering animal shelters do not have antibody to parvo or distemper. In other words, they've probably never been exposed or vaccinated.
Now, the point of bringing this up is in outbreak management. In the event there is an outbreak, we know that at least in the United States, there are numerous examples of individual shelters that diagnosed 2 or 3 cases of parvovirus in the shelter, and in order to manage the population, they euthanize every dog. Completely unnecessary if any of the dogs have an antibody titer to parvo or distemper.
So, the bottom line is, shelters in the US at least, are using this as a just in time type of management tool. If there is an outbreak, they will test to determine which animals need to be fostered. They don't have antibody, we need to get them out of the facility as quickly as possible, versus which animals don't need to be fostered and can be, can remain in the facility, because they are protected.
So you can see, what I've offered are some examples of how this antibody testing platform can be applied in clinical practise. I hope it gives you a little bit of insight. I think we need to perhaps learn more, do it more often.
I think there are more indications than I showed at the beginning. And are published in that paper that I can make it, that will be made available to you. But it is a unique resource.
It's a valid resource, and it provides objective information pertaining to the management of individual patients. So with that, I think I've run out of time. I think it's appropriate that we stop.
And I do have an opportunity to take any questions that you might have. Noga, if you're still online, we can do those. I am still online, of course.
First of all, thank you very much, Doctor Ford. It was really, really interesting. We do have quite a few questions.
We probably won't be able to get to them all, but I wanna try to give you a few. There were a few topics also that I saw a few people had asked. So, So something general about immunity.
With any vaccination immunity, there's cellular and humeral protection. How do we measure cellular protection? What is the protective cutoff?
There is no defined cutoff. Cell-mediated immunity is a function of the cell, the, the lymphocyte itself. And to measure that is done by lymphoblastogenesis testing in a laboratory.
It's very tedious and somewhat subjective in interpreting the results. So, it, there is no clearly defined cutoff. Other than what they might use in a research laboratory.
So, actually measuring To put it in perspective, Noga, antibody is critical. Antibody prevents disease. Cell-mediated immunity is what we use to recover from disease.
I think that's the easiest way to put it. We can measure antibody, obviously, but measuring the function of an individual lymphocyte is very complex and isn't done routinely. The technology just hasn't gotten to the point where we can define a clear cutoff.
Yeah. So you did touch on this, but maybe you'd wanna expand. How would you know how long the immunity lasts?
So for kennels or home boarding, the owner needs to know if the immunity still lasts at the time of the holiday. Do they require to have a test at the time of the booking and then again at the time of the stay? Very good question.
Given the fact that an individual, like in humans, the rabies, titers are all over the place in people. And we know the same is true with parvo, distemper, panleukopenia. Most dogs enjoy many years of immunity following.
The parvovirus vaccine. Same with cats that are immunised as kittens against panleukopenia. They may enjoy lifelong immunity, but Noga, we know that that's not true for every cat and every dog.
So the bottom line is, there's no clean answer for that question, but it raises a good point as to Is this a reasonable option for the client to know whether or not they need to be vaccinated, knowing that information. But I think it's fair to say, if you have a baseline knowledge that they have responded to a vaccine, you have an antibody level in the record. You know, they have memory.
If they've made antibody, they have B cell memory as well. So that's an advantage from that standpoint. Right.
We have a few questions about maternal antibodies. So let's do at least one of them. If we know that maternal immunity is still so high at 8 weeks, why are we vaccinating them so young?
And knowing that some are still not protected at the 16-week dose, why wouldn't we just start later and then do a dose at 20 weeks as well? Noga, this, this is a really challenging question. And the answer, I think, comes with the fact that purple curve of maternal antibody that I showed graphically, we don't know where it is in the individual animal.
For example, if it's a, an orphan pup, that eight-week dose will immunise the patient. With a modified live vaccine. A single dose will do that.
But we know that the, the mom dog or cat, the queen, may or may not permit nursing. They have to acquire that maternal antibody within about the 1st 3 days of life, in order to have a sustained level. After that, the gut begins to shut down and they ingest colostrum, but they don't absorb it.
So, the bottom line is, it can be highly variable, depending on how well the pup nurses, how well mom allows the pup or kitten to nurse. Too many variables in that equation. So, generally, we find that recommending 3 doses, and in high-risk parvo environments, we do recommend a 4th dose at 20 weeks.
So there is that option to do that. And I think the antibody testing gives you clear visibility on where you are in that individual. Right, right.
So this is always a great question. How does long, you touched on it a bit also, but how does long-term pred treatment in chronic dermatology cases affect response to yearly or triannual boosters? And does that vary depending upon which vaccine?
Interestingly, it doesn't. Long-term dermatologic use of corticosteroids, for example, are at a relatively low dose. And the studies done in dogs, cats, interestingly, horses, And a lot of studies done in humans show that there's a negligible effect of corticosteroid therapy at these lower doses on antibody responses to vaccine.
On the other hand, long-term treatment with corticosteroids will impact cell-mediated immunity. In other words, the ability of the patient to respond or recover from an infection. So, that's the downside.
But the data today is pretty clear on that in human and veterinary medicine, that, no, I wouldn't worry about it. If they're being treated with corticosteroids for it. Dermatologic problem.
It's a relatively low dose. Vaccinate them, and don't worry about that. It would be interesting, Noga, this is an interesting point.
If you did vaccinate them and measured their antibody, looked at their antibody levels to determine whether or not they're responding to the vaccine, my guess is they would. Yeah, absolutely. I've had actually that question by a few veterinarians that they're doing long term treatment with pred and kind of were asking me also, should I titer test during the treatment?
Should I titer test after? And yeah, it depends what, what you want to know, what information you want to get out of it. So, definitely.
Another good question about puppies, do you recommend breeders use nomographs to plan vaccinations for litters? We have looked at nomographs. I'm not a fan of them, to be honest.
I think the protocol that we've laid out. And it varies. The UK has a different perspective on that, the early Finnish versus the US.
So there are quite a bit of international variations on the juvenile series. The nomographs, I think, are a general broadcast of how well or when to do the vaccines, but I don't know that we've created a problem by sticking to a standard prescribed protocol. I think we're doing very well with that.
I do like the concept of testing them. If these pups are going to be sold, knowing that they've been immunised is probably the best value. I think that's more objective than trying to use a nomograph.
Personally. We have a lot of great questions, so I'm trying to choose a few cause we don't have a lot of time left. And are there any future studies planned to look at the possibility of extending the three-year vaccine recommendation?
It's an interesting question. There actually have been studies done. I wanna make one thing clear, the only requirement to adhere to an interval between doses of vaccine is for rabies.
Veterinarians legally have the discretion to use any interval they want. So you could conceivably base it on antibody testing rather than routine vaccination. That is done, occasionally.
If, if the owner is particularly, really hesitant about having boosters administered on a routine basis, but yeah, that, that is an option. It is being looked at. But I think the, the value added of having the patient come in for routine vaccines, medically is an advantage to the patient and the practise.
So, I don't see it being adopted anytime soon. Although we know most dogs, most cats, for core vaccines, enjoy a long duration of immunity. All right.
We got a few of these questions. So I will bring it up again. How often, how frequently do you recommend titer testing?
Again, we went through a series of indications. It really depends on what you're doing it for, Noga. I think you and I would probably both agree on that.
Yeah, personally, I do not see a primary purpose of antibody testing as a means of replacing vaccination. I think it's a supplement to that. And verification of immunity under certain circumstances, but I really don't do it on a designated interval.
I do, however, advocate a baseline. Knowing the dog, following the initial series has established its baseline antibody response, and it is immunised, that should be assurance the dog has memory. And the dog also has a pretty long life of protection, right there.
So, I don't really prescribe to annual or triennial antibody testing. Mhm. All right, let's do maybe one last question.
. I did get a few. We do have a few about. The lepto vaccine.
So maybe let's answer one of those. Sure. OK, hold on, let me find the one I was looking at.
Why is titer testing for lepto not correlated with immunity? You know, probably noted the same reason that herpes and caliciviruss are not. Lepto is a significant cell-mediated immune response to leptoimmunity.
And we're looking at lepto titers as a diagnostic tool, rather than, it, it just doesn't reflect immunity. Dogs have tighter, but they're obviously not protected, because we're using that as a diagnostic tool. And, So clearly there's no Protective immunity conferred for lepto, when you, if you measure that immunity, that antibody level, and it's positive, it really is more indicative of infection than it is protection.
So, no, it's, it's not gonna be a, a protective indicator, a good licence. You just have to vaccinate and hope it works. Yeah, absolutely.
OK. We need to wrap it up. I'm sorry for the questions that we couldn't get to.
I wanna thank you again, Doctor Ford. If anyone of the viewers would like more info about BoxyCheck, then you can visit our website at www.biiogal.com or you can also write us directly at [email protected].
One last thing, for all the viewers, you will be receiving a recording of this webinar and also a CPD or CE certificate within 24 hours. Thank you again, Doctor Ford. Thank you for all the viewers that joined us today.
Have a great rest of your day, evening, night, wherever you are in the world, and thank you so much. Thanks. Bye.
