Dr. Dryden Webinar Recording (2023-09-18 12:12 GMT-7) - Transcript

Transcript

This editable transcript was computer generated and might contain errors. People can also change the text after it was created.

Melissa Schalles: Today, we have with us Dr. Michael Dryden. He is the Distinguished, professor emeritus at Kansas State University. Dr. Dryden has about a hundred and over a hundred and fifty, scientific research publications. He's performed over 1,500 different lectures in over 22 different countries and he is the winner of numerous awards, Dr. Dryden, We appreciate your spending the time with us today and welcome.

Michael Dryden: Thank you very much, I appreciate the opportunity to talk about this really important topic today. One that actually is incredibly clinically relevant and one that and quite frankly is a little bit scary when it comes to how we deal with hookworms and dogs. So, obviously, I'm gonna talk about Antimic resistance in Ann's, lost McCain, item, an emerging threat. And this clearly is an emerging threat and is only going to get worse for the next several years until we figure out a way to really manage this extremely well. I'm gonna talk today about What I think, maybe the best way currently that we can do this very important parasite.

Michael Dryden: But no, before we get to that resistance aspect, which is going to be, obviously a major focus of this obviously, with do a little background because we've got a little background on understanding of the hookworms and dogs in order to basically understand how we're going to manage this. So we really got two important hookworms in the United States. When it comes to dogs, they are ants lost, McCain item. The classic dog hookworm. And we've also got Unscenaryist in Encephala and we will briefly talk about that. There is another one out there and philosopher. Brazilian say it's a true southern form. It has been found in Dogs and cats along the Gulf Coast states into Florida. But in all honesty, we know very little about this organism. It's amazing how important this cookworm is in equatorial zone throughout the world.

Michael Dryden: But we just don't have a lot of background on its biology. So we think it's probably fairly similar to and Sauce McCain item, but that would just be a guess. So today, I'm gonna have to focus on ass can item and briefly on scenarios to Encephalop and that matter.

Michael Dryden: Bookworms are really pretty common and you look at these national surveys that they do and they say hookworms, it could be and so lost going in there, some months in area, could be Brazilian say as well, but whatever it is, hookworms are pretty prevalent. And if you look at these, various demographic situations of further south east, you go, the worst it gets, and they're on the West coast where it's dryer that tend to be lower incidents, but whatever it is. It's in shelter dogs across the United States about 20% of all shelter. Dogs have an philosophical in scenario. If dogs are coming into a veterinary practice and they're adult dogs and they're coming here for annual visits, it's actually further low about two and a half percent, but if dogs are going places and doing things like dog parks,

Michael Dryden: Is up to about seven percent of these animals. In a national nationwide, survey of over 300 dog parks about seven percent. So depending upon the age of the animal and the lifestyle of actors that animal, and of course the geographic situation where you're at, it's going to fairly dramatically across the United States, but no matter where you at dogs, can't get exposed hookworms and their lives. Our problem, we're going to talk about this resistance issue here, again just a few minutes. Understanding that and we'll talk about this, it originated out of the Greyhound industry, but it's now rapidly spreading because we tend to take our dogs places and we tend to do things with them. And now it is spreading very dramatically into our pet dog population.

Michael Dryden: So we need to talk about the life cycle. This parasite a little bit because this is where some of our confusion comes in and some of our diagnostic dilemma. I exerted this diagram out of an old Georgie's, textbook, event comparisonology, really fairly complicated for that matter, and all honesty. But what it really is trying to represent is something actually over here, in these Five Points. Number one, How do dogs get infected with hookworms and sauce became items? Specifically relish your appear. they can't ingest the larvae by basically chewing in the dirt chewing on grass things like that. The larvae can be in Fairly commonly. they cross the skin skin barrier and get into the

Michael Dryden: Circulation and only migrate to the gut. We call this percutaneous That's our really common mode of infection of a lot of species out there in nature dogs, lay down in the sand exposed England region or through their foot pads, and these larva connection can drink fairly rapidly. Transmemory. This is really, really common in puppies. sometimes during the life of that female, dog. these larvae get insisted in somatic, tissues. And then when she gets pregnant and then she starts to lactate these larvae rule migrate and cross over in the milk. And in fact, these puppies it's a real common mode. Unlike roundworms like toxic Carecanus, there's no trans for several transmission with hookworms. That does not happen. There's no transplant transmission with ants lost McCain item. It's Transmemory is a main means of infection to puppies.

00:05:00

Michael Dryden: A lesser known one out there and there's only been a couple studies ever done and they were done way back in the 1960s It does appear that Parente coast like rodents and cockroaches. May also play a certain role in this probably not as much as it does with roundworms. But there are some evidence that this goes on that, these animals, particularly rodents, can't even get affected by these larvine nature and then if animals a dog preys upon them, they can pick those large be up. And those are because then migrate but we don't know much about that. And all that's the only two studies way. Back the 1960s, the other one. That's very important to us. And this is one that confuses us when it comes to resistance. And that is what we call larva leak or leak back. and this happens when we have larvae that are insisted in these tissues,

Michael Dryden: And then for various reasons, they become reactivated out of these. insisted stages and completed migration back to that gut, probably going back through the lungs through a Draco, migration route, and completing their way back into that small intestine. various things can cause So a dog later like female pregnant and the stress of pregnancy. Hormonal changes can cause reactivation larvae just normal stress patterns and we've seen this dogs that are shipped can actually have that or dogs that actually have surgery. And then after the fact, because of the stress associated with that can have some reactivation to larvae.

Michael Dryden: again we mentioned the transport. There's also been some good studies showing that a dog's having intestinal infection, that antibody response. Actually, you keeps the larvae insisted and you deworm them, we warm those dogs and then some of the lobby become reactivated and can we have the reasons as well? This is really common in greyhounds and we're not sure quite why. In fact, there's almost universally common in the Greyhound breed. Not so commonly in other breeds but it does happen and it has been documented, but larva. Leak is important. So we basically have five ways that dogs can get intestinal infections, if you will ingestion of Barbie, percutaneous of basic, transmission of warby across skin barrier, transmemory infection in puppies.

Michael Dryden: If they pray upon some animal, like a rodent and simile data cockroaches, which again, has been documented and then this Lord will eager leak back. So there's multiple ways that dogs can get an intestinal infection with these hookworms. That's lost. Also important years to recognize it There are what we call prepayton periods, associated with these different modes of infection. as early Some as long as by four to five weeks, but quite frankly, you never really know how this dog. It gets infected. So we need to remember from the time. A dog is infected. These worms could potentially mature and be shedding eggs. In a short isn't about two weeks, And that's an important number two weeks. We'll come back that a little bit later, I want to reiterate. This one's kind of interesting.

Michael Dryden: And Sloth McCain item, This hookworm is the only known nematode parasite that undergoes larva lee from somatic tissues to repopulate the gastrointestinal tract, There's some protozoa that do that and we know that that happens, but when it comes to other nematode parasite does this that is that larval leakage back. that small intestine. So it's really pretty unique for this one, parasite.

Michael Dryden: on scenario the far, less common hookwormer dogs. United States, much simpler infections are probably acquired primarily by the oral route. Yeah, there's probably minimal to no percutaneous absorption, there's no transmamory transmission. at all the eggs, a little bit larger, I'll show you a picture that a little bit later but being fairly similar about two weeks and this is his historically a more northern adapted parasite. We know this but the European situation where we're shortly found in more northern areas of Europe. And in fact, it's the only hope from this endemic to the United Kingdom in the United States that really doesn't fall like pattern. Because there's been so much movement of dogs, people tend to move snowbirds into move, a lot of northern to southern states and you really don't find that northern to southern basically distribution like you do in other parts of the world, But it is a more

Michael Dryden: Adapted, species, truly is in a mixed infection. If you have a bunch of eggs in feces, if you take that fecal mass and you chill it down to about freezing, zero Celsius, 32% degrees Fahrenheit, all the amp sauce, McCain Idaho eggs will die in the unscenary eggs will survive. So it is truly more northern adapted species in most places in the world.

00:10:00

Michael Dryden: But in the United States it's really fairly in common and you can see here even in the southeast, it's still the highest prevalence. But again, a lot of those probably dogs are red rated the north and then came south at some point. So there's not that northern South Southern distribution but what we do all do know and this is very important is the level of a scenario is significantly less than the level. We see Nanos McCain item. In fact depending on the region of the country it's about seven and a half to 29 times more prevalent. That is an slothment, then his engineer. So it's really the most important one that we deal with out there,

Michael Dryden: From a pathogenesis standpoint ending. And this is important because we can't manage ants and salasma will manage our dogs. In other words, they can kill dogs. So ants, lost again on him is a highly pathogenic blood feeding nematode lashes on to the microvill Consumes anticoagulants even after warm moves from spot to spot to spot this year's behind it, continue to bleed and significant amount of blood loss can't occur. There's been two studies looking at this and I thought the range was kind of huge so I'm not sure exactly. Where the number actually is one study said that hookworms consume about a tenth of an male ML blood per day for the study said eight tenths of an ML of blood per day for worm. Again that's a huge range.

Michael Dryden: Are a full differential, but whatever it is, it's significant and sadly, those of us who've worked in this arena record, the scene dogs to come to massive, hookworm infections. We know that. Okay, and I've seen puppies that have succumbed to this with just met, massive hemorrhagic diarrhea and it's not just the adults it can do this. The actually L4 is before they melt adults in the intestine can actually do this. and in fact, these tissue sections, here are from a puppy, that died of what we call parachute hook, or anemia death due to The immature kill this puppy, even not the mature worms. In fact, in that one slide set of over there where they see that millimeter scale. There's only one adult there but there are dozens, in fact, you go through the entire intestinal tract, thousands of immaterial force that hit this dog and we're killing this dog. In fact, this puppy speaker was naked. So again, pretty massive larva load.

Michael Dryden: Dog and in this dog to come fairly rapidly. in scenario, on the other hand, again, it doesn't occur very commonly seven and a half to 29 times less frequent than ants lost but Daughter, that is actually not very pathogenic. And in fact, the American Association event REPAIRISTOLOGIST on their website. Says, It's probably the least pathogenic of the firm infections. There's been some studies out there. It may only consume one to two percent of blood that ants lost me. Does some textbooks says it's mild, even non-pathogenic and quite frankly gets real hard to find reports out there even a European literature of clinical disease associated with unscenario with massive infections. in dogs, In one study, they had minimal, pathology some protein, losing interopathy, some optimal growth, but that was with a massive, horrible infections that occurred. So,

Michael Dryden: Even though it does occur very often. We're actually not too concerned about anyway because it's just not that very pathogenic in our dogs. I guess we're pretty fortunate for that. And almost be honest, if you run in a vehicle and you see hookworm eggs, I mean, how many technicians are veterinarians out. There are going to differentiate ants lost bags from the slightly larger on scenario eggs. We got something around 70. Microns a little bit larger. I'm just not sure. Most of us were with every recognize that without a lot of training, all honesty. but again not to be too concerned. So when it comes to hookworms, historically we know we begin treatment and puppies about two weeks of age. We try to help minimize the viral contamination, entry that ppy as well. The puppies on monthly preventives as soon as the labels allow and administer these broad spectrum parasite products

Michael Dryden: With FJ against hookworms and other parasites. Of course, round rooms as well, roundworms and maybe whip worms and of course, heartworm and keep them on these products throughout their life, to protect the animals and minimize amount of ants loss percent the environment.

Michael Dryden: And because We're not only trying to protect the dog, but we're also trying to protect, human population in particularly the family, if possible. So, these recreations have been out there for a long time. Adopted by American Vet Comparistologist, the CDC also recognizes he recommendations as well as organizations, like, and Ava. So these are pretty, why they recognize recommendation out there historically and this is really work really well for us. Okay, so in that regard again, a few more set up slides here. If I've got a normal puppy that comes into my practice and it's eight weeks of age, which of the products here that I've listed good idea, we're in that puppy with which means that in order to get a product approved, the United States by the FDA

00:15:00

Michael Dryden: As a parasiticide, when you administer that drug, you need to be able to kill. weren't population in that dog. with a single dose. Again, it's a 90% threshold. That is always been basically recognized by the FDA to get drug approval and you're gonna have to have at least two laboratory trials and a field trial in order to get this drug approved. So, which of these products we got advantage multi or the generics John gel plus heart guard, plus the various generics, they're very interceptor. Formulations nic here. Mx canon revolution, the sentinels spectrum products out there, some parent trio trifexis, and of course, we now also have next guard plus, which I probably need to add to the slide almost there right now next guard plus as well. So of all these, I've got the A through J. And now we get add Kay as well. Next guard plus, which of these products out there are actually label.

Michael Dryden: And effective to deworm a puppy France. Lost McKean item. the answer is everything but Does not the Transdermal canon revolution, just not achieve high enough, blood level solemectin to have in. Again, sell them back in, is basically taken by the liver and it treated unchanged into mile and they're just not enough of it being dumped into the bile in order to get that job done in the dog. And again, I don't have K. This list which probably should have, but we put this together before that product got approved and that start plus, we do it as well. So basically there's a lot of products out there that are extremely effective Deworming a dog normally. For ants lost McCain, the other part of this is again, we got to get this groundwork done before we get to the resistance aspect.

Michael Dryden: Historically we do see positive beagles in dogs that are basically being given these monthly broad spectrum products. So how can you have a dog on a monthly broad spectrum, Macaulay product? We're talking These monthly administered heartworm products that also have activity against ants lost them. How can you have a dog on this given him on monthly product and still have a fecal pop-up positive for hookworms. Okay, and this hat has happened, historically way before we dealt with the resistance. we got to go back to some things we talked about earlier and that is the prepaid period that is in the time. A dog is infected. Until that were matures and is producing eggs. We can detect in the fecal. Remember that can be as short as 14 to 15 days depending upon the round of infection and since we're given a product once a month, once every 30 days, it was not, uncommon

Michael Dryden: for people like myself a betteristology, get a call from a practitioner. I've got a dog on Heartgard plus, I got a dog on interceptor, whatever it may be and I've got a fecal. That's got a few hookworm eggs in it. Not a big deal, all honest is give the next dose and go on it. Just the fact these dogs are getting a lot of exposure.

Michael Dryden: You've got a positive equal. Thank goodness. We had him on that product and we were doing a good job of maintaining that, Because remember that that can happen. Historically, the other thing that happened is when I just came out with their fecal antigen technology, a few years ago, looking at people antigens around folks and whips. and now they got additional parasites as well. We saw this positive People antigen test and they actually published to the shows that these extra choice. You go. Antigens can be detected is really nine days after dogs. Infected there were managing. They're not We're antigens that they're being very rapidly. So yes, even with the idea to be gladogen test, you can come up with a positive vehicle on them, on a monthly product. And then we know that happen. And the other thing, it happened as a dog. Might just eat other animal species and dogs are highly couple of major and the' In fact, it in eggs can be going through. So historically before we got to the resistance issue, historically,

00:20:00

Michael Dryden: Several reasons why we might see a positive fecal. In a dog that's on a monthly broad spectrum, heartburn prevent so in these things we've talked about historically for, A couple decades with prepaid period copper AG and more recently in the last five years or so with the Atlanta just but it's been out there and we knew that. that's our groundwork. Now we need to move on to The newer issues now, so chronic hookworm cases. So, several years ago, and I can't tell exactly when that was, at least five years ago, probably going back a little bit earlier than that. And all honesty. Maybe seven, eight years ago. Now, we started seeing an increase in what we call. Chronic Oprahome cases, not just the ones that popped up now but we started to see more and more. These Initially, they were almost excrucially in retired, racing grounds.

Michael Dryden: But then as time went on, we start seeing the other animals as well. And initially we kind of struggled as to why that was. But ultimately we now recognize, we've got some issues here. So we've got to walk through these whole scenarios. So Yes, there can be several reasons why dogs have chronic cookware problems and we've kind of talked about some of that historically, but we need to go through this again, Because we got to build up to this to make sure daughter eyes and cross our Jesus is important from a clinical standpoint. So first of all, is this dog living in A contaminated yard. Is it going to a dog park? Is it going places? Getting refected on a regular basis? Okay, so we've got to ask some questions about the lifestyle of this animal because remember the repeating period is shortest, two weeks.

Michael Dryden: And many of these heartburn products were giving one same month. And so they communication to get reinfected in shed, eggs, between monthly dosing. We know that's a reality. So let's just ask some questions about that, there's ways to figure this talk about repeatedly I mean in order to figure this out is this a contaminated yard or this resistance? You run a fecal positive give your dewormer come back. 10 days, two weeks later on another vehicle. If it's a contaminated yard

Michael Dryden: They should be gone. He killed the worms and it's too soon according to be reinfected to be shedding eggs So that 10 day to two week, post treatment reduction, test, basically it's really fairly simple to do that. And again, this is the common thing we do to figure out where this resistance, or some other issue begin talk about and ask questions about. Where's this dog going? What does this dog doing? Okay, copper phasing real common. I mean, I've seen this many many times. Let's face it Eat other animals feces. They do it really pretty regularly and one of the things they like these, you like to eat large animal feces and so mean the cattle sheep, goats things like that horses on farms. But deer commonly live within urban environments anymore. So if a dog got access to these things or eating them on a routine basis,

Michael Dryden: Many of these animals almost universally infected, what we've called strong Giles, that's the large animal, strong gile, be that in ruminance, whether that's ostrichia humungous, various superior, whatever, it may be very other room in it some of the equine, small, large, Sean Giles and horses. Those eggs look fairly similar to an ants lost mag, which in fairly similar, family strong idea, they're very similar family. So those eggs are passing through, And they're not actually infected you go. So first of all you got to Identify the eggs has lost my leg? Or is it somebody larger? Because most of these tend to be much larger that can be hard to determine sometimes just board this animal for a couple days. What all that pass through, and look at a fecal boredom on a Friday night. Looking at people on Monday. It's negative that was Copper Veggie or have the aunt or have the owner. Put this animal in a place where can eat animal feces, okay?

Michael Dryden: The other thing works really good is a fecal energy test for my decks because fecal and idex will differentiate Is this a anselosma fecal antigen or there's no antigen there at all. So the idx vehicle energy test will quickly tell you whether this dog is actually affected with anceloster or not or whether these eggs or something else, So there's various ways of figuring out as this copper Beijing. But again, This happens a lot that there's a really cool study there. I think it was done in Switzerland a few years ago and they found that in 30% of Dog fecals that on visual inspection when they did a big ass. Centigration did a fecal looked out of the microscope. In 30% of the dogs had positive eagles. There were actually cat hookworm eggs in those vehicles. Because they could do this with PCR 30% of dog fecals that had eggs in them.

00:25:00

Michael Dryden: Some of those egg cat before makes dogs only effect with ants lost. But two before me those dogs, drinking cat feces, so it's not uncommon that copper page, you can be potential issues. So again What's this dog doing where it's going? And there's a few simple things we talked about here, you can do to differentiate this and boarding the animals, and simple way to do that or the ideal energy. Yes, will tell you. Is this dog actually affected or is it not infected? And then the leak back problem. Real common in retired racing greyhounds, rarely other breeds. But I've seen a number of cases over the years and other breeds as well but really leak back that larva leak. These dogs have these insisted somatic tissue burdens.

Michael Dryden: Larvae required throughout their life by being raised wherever they're being raised. Some of the larvae populate the gut, some of these larva be going to somatic tissues. We remain there, the life of these dogs and under those various situations we talked about earlier pregnancy, Stress transport Prolong boarding, Boston, Current tests on infection, some of the RV, some of them will become reactivated and repopulate that gut, and it can look like your monthly products aren't working. Or you might give a dog you'll draw until panic here or interceptor. And then come back, three, four weeks later and run a fecal, and they're positive again. So, it looks like our products aren't working and initially it can look like resistance again, there's ways of figuring this out, first of all. You've got one of these dogs that. Yeah. I'm seeing positive equals. We said it before.

Michael Dryden: Treat the animal. Come back 10 days, two weeks later, run another fecal. and it should be negative again, I've given the dog until mythic Come back 10 days, two weeks later, run a fecal and it should be negative and come back again in 30 days and sometimes you find a positive again that again, they got reinfected that larva league is leaking back in the situations. So during that time frame, you got to minimize your possible exposure, out there in the environment as possible, but really pretty common here and again, if it's just leak back and you warm them, two weeks later to see who's gonna be negative. Okay,

Michael Dryden: We've often seen this in dogs that have kind of a repeated positive equals over time. they're positive or negative positive because you're killing the ones. Then sometimes later the larva leak back again more common. In retired racing greyhounds, you've got to initial when you got a differentiate from resistance and all talk about them more later. But again, really not that difficult to figure this out. Because if you deworm them and you come back, two weeks later on a vehicle, it's gonna be negative if it's Laura leak. Could you killed this up the worms? And they haven't leaked back yet and matured yet in order to have a boss speaker again so it's not that difficult. So when we have one of these, chronic larva leak dogs and again we dealt with it. These historically for decades we've known this raw and particularly in greyhounds which is really common in pride racing greyhounds, almost universalism. We've had really good luck using topicals.

Michael Dryden: Transdermal advantage, molting, moxide metaphor. We also have generics like a moxie, I say topical transdermal we need to recognize and we're putting moxie decked in based formulations topically on a dog, they're actually transdermal because the moxide is being absorb systemically and in working systemically. So that's transdermal, topical application, they'll slow, normal shorts and half, life of the formulation allows a steady state of machinectin within three to four months and that's what we're after the steady state. And I'll show you slide here in just a moment. And we suspected this high studies ahead and mark to death. And it's achieved after three to four. Doses, is killing these insisted larvae once they are reactivated, We're not killing the metabolically, dormant insisted Laurie. We know that, okay, we're not killing them, we're killing the ones that become reactivated before they can get to the And we're really, really Now, we also recognize that sometimes we can increase the frequency, we can go days,

Michael Dryden: So 1430 instead of monthly we go zero fourteen, thirty, then monthly and that's really very safe to do in these dogs as well. If you want to try to get that steady state a little bit quicker. Okay, so far this has worked really well for us. Egg counts. Usually drop sometimes a zero within 30 days. So some dogs can actually take a couple two, three months before it gets down to zero but generally within three to four months, these dogs will be negative if it's just leaked back. Okay, I'll be honest with you, I haven't been able to fall every case up. I always ask that Marion should call me back. The general economy back of things don't work in all honesty so a lot of cases lost to follow up so I can't tell you it Is worked in every link back case. But I think it's worked in the vast majority of them.

00:30:00

Michael Dryden: One case is important here that kind of reiterate some of these issues. So we had a retired raking ground certain number years go up in Omaha it really classic chronic egg shedding regardless of Royal Enfield views. if you go negative positive and then come positive again. Then you treat to go negative composite again this kind of repeated positivity over time. Okay you can think you get the vehicles negative but they'd always come back. Okay, so we put this dog on advantage multi we talked about before. In fact this dog, we did zero two weeks 30, 30 days, then monthly thereafter vehicles went negative within three months. People was negative with kind of what generally happens. They kept the dog and advantage multi for a year and then much They did this, but the dog was taken off advantage, after a year.

Michael Dryden: Put on another oral heartburn product, and two months later, the fecal repositive again, okay, dog was placed back on advantage, multi on a monthly basis and egg setting, cease pretty rapidly. I'm not sure how long it takes to eliminate somatic, burden, in these dogs. Don't know. Year wasn't long enough again, because we're not killing Dormant insisted larvae. We are killing Larry wants to become reactivated. So based on that, particularly these once we have a larva league greyhound, I just stay put them on advantage multi or generic like a moxie transformer oxide product. For life because we just don't know, it just easier to go that way. That would be got Prevention ground hooks and whips and we got it covered in these dogs for life because I just don't know how long until we can pull them up, but I'm on something else.

Michael Dryden: Okay, so the other question that comes up, often is, Can I use injectable moxidectin to achieve the same results? Prohard 6 pro, her 12. Okay. there's never been head studies done. Looking at this, but you can go back and you can pull up the published date on the farmer, go kinetic. So this is the pharmacokinetic profile of cohort chicks. Okay, showing that about day eight, we're kind of peaked out just under five nanograms per ml in these dogs and then over the course of the next number of months, 112 days. We get down to point seven five nanogrammel and this is what that monthly application based upon the farmer who

Michael Dryden: They've been published for Advantage, Multi look like, and you get out there at the end that 112 days. We've got almost, 30 fold higher, blood levels of machetected. So that's what we were after that long term steady state. As you can see, you get out there at the various doses out One dose, two, three, four, doses. You get out there to steady state about 21, 22 nanogram for ML. And as long as you maintain that dosing, you're gonna maintain that level. And that's what we're after. Maintain that high level of mock detect, anytime you start making reactivated, we're killing them. And that's not what we're getting with, Bro. Hardships.

Michael Dryden: there's only been one study that I can find with prohart 12 and believe it or not, in this study, they were looking at a bioaccumulation, so they give it once every So they gave pro heart 12 once every six months, okay, but that's The bottom line is, you look at that hundred and twenty day, 112 day profile and we're Between one or two nanograms again, it's just still I high enough dose, it's less than two, so that's tenfold less. So cohort, 12 doesn't give us that the level of much addict and that we're after in this situation, We don't have bile Cumulation studies yet, with oral moxidectin, either next guard some character trio at 24, or

Michael Dryden: Or higher nanogram, basically milk and makes per cake when those formulations, I think once twelve and one's 24 orally, we just don't have that data yet. I know single dose, we're not going to get near that high, we know that, but what kind of bug in which native, we just don't have at this point. So for now, I got to stick with the topical, transdermal medical formulations like advantage multi or moxie or any other generic there might be out there. Okay and finally this is what this was all about, right? Anthony Resistance.

Michael Dryden: documented, okay, and I've given you a list of the studies down there. We've now got seven published studies and there may be more not coming all the time. So we now have seven scientific studies that have been published on Amazon resistance, I mean, that's lost canine. So we know it's out there, this is a major problem So some of these dogs are truly multi Antimic drug resistance madrs. So resistance in Benazola has been documented. my son has been documented, parental has been documented, Machin has been documented, and I've Remington has been documented.

00:35:00

Michael Dryden: Resistance to all those and in some dogs, multiple combinations of these as well. So, some of these dogs are truly madr and that's the problem. The other issue that we're facing is that we don't have good genetic tests for this. benzemit has all resistance test. For the 16s 167 y and the Q134h genes but we don't have them for these others. We have no genetic tests. Remember Myison irondale match addicted ivermectin We don't have that. Antac has been Zim is all resistance green. That's good. It tells us that they've only got it for one allele now just the 167, When that's all when we've got. So it's a nice task. But it doesn't begin to answer the questions we need because there's so many alphabetic issues out there as well, okay? We know the started on Greyhound farms.

Michael Dryden: With the massive exposure, these dogs are given a Greyhound farms. These dogs are raised on Sandy soil, types situations, great for hookworms. They're administered large and helmetics on a rotating basis weekly and then monthly for life, bombarded in a confined setting.

Michael Dryden: This is a beautiful resistant scenario, selection mechanism. The resistance did not come about because of us giving broad spectrum products to our Dogs out there, did not. We know that this is a Greyhound farm situation and then radiated out at some point, this will cease because the ground industry is basically almost non-existent. I think there's three tracks left in two states. So this industry is dying. If there's eight nails in a coffin, seven have been driven in. but still at some these dogs are still going out, but it's too late on these dogs, went out into our homes. These dogs went out into City parks other places defecated. And this is spreading rapidly publication. Now a couple years old, they found it in 21 different dog breeds.

Michael Dryden: Yes Madr has been now found in 21 different dog breeds. That's not good and that's just what we know. And so basically the horses around the barn and the barns burned down, we getting this wink in this back. When we're not getting the genie back in that bottle, it ain't happening. This is only gonna get worse, there's now actually been a really good publication. Were Res of found in a Labrador kennel. These dogs are multiple and antimic resistance in them to multiple different products, but they were able genetically trace that somehow we don't know exactly how

Michael Dryden: It's Greyhound source. So somehow a dog came in there was exposed to greyhound feces at some point in contaminated larvae. But they can trace these back and it genetically traced back to the ground source. So grounds tend to be original source, but now it's going everywhere, this is not good. Okay.

Michael Dryden: If you've never been on a Greyhound farm around the ground industry, we did a lot of work here back in 1990s, looking at antomething Warm issues in Greyhound farms. And so, we were able to get access to these farms and this is the actual deworming protocol from one ground farm. There was near Abilene Kansas. This is a dog farm that had over 500 dogs on site at the time. And as you can see here, this is just an incredible array of antimics large animal products. We have $500. You're not giving small animal that they can't afford it. So they're going to the local farm and feed store the co-ops buying these products, and just doing that at these dogs. Everything you throw at them, multitude of ray of these large animal products and really try to remarkable. And again, you can think of, every category event out, there is being with strolling at these dogs. In a confined setting Again, remarkable resistance, selection scenario,

Michael Dryden: how do we figure out from all those other issues? Do we talked about before copperphagia exposure leak back? How do we say This is truly a resistance case. Here we go. What we do is Obviously you got a dog's, got a positive, Okay, you've dewormed it before with that of a product, it is and the vehicles positive. So what we've got to do is you're gonna get a fecal from that dog. And you're going to send it off to it to some lab and here I got the information for Idex but others will do it well and tech will do it. Various research institutions that have been schools to do this as well and I'll come back to the idex thing here in a moment. You send it off to that lab and you say I want to quantitative equal exam.

00:40:00

Michael Dryden: The standard one you get is called a qualitative, negative. Okay, I want to quantitative equals am where I can get the numbers of eggs per gram, and you're gonna result back 500,000 5,000, some number eggs, per gram of feces, and what you do is, you minister The correct dose of your antoinic, whatever. The implementing is your concerned about And then you come back 10 to 14 days later, get that dog back in collect and have the owner bring in a fresh fecal, send it off as well and get another quantitative equal exam. And what you're after is you want to know what percent decrease in numbers of eggs, do we got what we want? Generally is at least 95% reduction 90 To 95% reduction. You can look at the publication. They talk about what 75 or less means? Okay then yeah, little too complicated.

Michael Dryden: I want a 90 to 95% reduction in the numbers of eggs in that dog after a single dose. I'm pretty happy. If I'm not getting that, I'm not happy. Means you're probably doing with the resistance scenario, again with idex really fairly simple, their code for their basically quantitative people exam, epg is 17002. Here it is right from the record laboratory and here's the link and they give you the number bags, reported per gram. They takes about one or two days to get it back. They need about 10 grams, that's not 10 fresh species, 10 grams is right back about the size of two Hershey's kisses. Okay, so it's not a lot of feces, but it's more than a fecal loop standing to them, and they will give you back that epg. so the people off

Michael Dryden: Deworm ten days, two weeks later, get another fecal, send it off. And I want to see that 995% reduction in number of eggs. That's what we're after. If we don't get that, we've got a problem, So, if post treatment account reduction is not 90% and we can expect resistance, In that product. and that's the issue we have, Once we have one of these cases that is resistant. we can try different antlement things. maybe it's resistant to power tail, not to tremendous all may position. Finn bin is all not to oxide. We can play that game. If you want to that, you can do that piecemeal game. Generally what we do, once we find one of these cases is We're going to administer some kind of moxidectin medical, transdermal product with some kind with John, tell plus. Okay, here's the key. A lot of these are.

Michael Dryden: Hill Prevented all resistance, some of them are resisted to two enemies at once. But rarely are they resistant to a parent telephone all at the same time? It has happened, but that's fairly uncommon. So generally the resistant to one or two classes, the drugs at the same time. So what we're attacking them with is we're attacking him with a three-pronged approach box, addicting actually, black, don't draw until plus.

Michael Dryden: Tyrantel. And if a bantel and draw ontoplastic converted tooth in benidazole. So the different approaches are I give them transgender machinectin and John tell plus, or I give them transdermaloxidectin been ben, isol, and power until separately. If you got panic here and pyrantel on your shelf, so you can go either approach. But you're doing the exact same thing because John tell plus contains pyrotel and for battle and the liver converge a bantle tooth in benazol. So, basically multimodal approaches here, one or two, Or really the same. Okay, so In the study that was published out of Ohio State University. They gave the transdermal topical advantage multi with drawn to plus and they built in 24 hours apart, And what they do is you administer these things. That combination monthly Until the fecal is negative.

Michael Dryden: Once it's negative, you pull the animal off of the drawn tail plus and keep them on the Topical, transdermal moxadecimeter, corporate advantage, multi for life. And then you check because repeatedly and if it comes back positive and it can add the drontal plus back into it. Until it goes negative again. In the vast majority of cases. This has worked. because rarely do you find these ants last minute that are resistant to all three classes of the drugs at the same time. that's why However, it doesn't work every time. And there have been documented cases where this has not worked because these are truly madr.

00:45:00

Michael Dryden: Reclasses of resistance at the exact same time. that's not good. So, if you've gone to out of this multimodal approach, we just talked about, you've done this for three to four months. If equals don't go negative, we're not knocking these egg counts down. It's not looking good at all. We've seen that now, it means resistance to Ben Simmons, always resistance Jack magnetic Blackstone, same time now. We got a problem. There is now been a publication that has documented the use of the topical, transdermal cat. Profender Given orally to dogs at one third, the cat dose. this is a difficult thing to talk about, in all. Honestly, I'll be honest with difficult to talk about, The drug is in middle peptide.

Michael Dryden: We have no approval in the United States for a middle pepside in dogs, is approved for dogs in Europe as an oral product. It won't work. Topically in a dog, like, a dozen a cat. So, in Europe, it's an oral tablet. We don't have the United States. never been approved in United States, so, we're talking completely unapproved drug here. We're only going to get to the use of the topical. Cat. Profender product orally in the dog. After everything, we talked about today Everything has failed. And in fact, what we generally recommend is before you do what. We're gonna talk about here in a moment, you contact a veterinary peristologist, maybe me or some veinary, paristologist, did some veterinary institution near where you're at, to have them help you through these cases. This is very important. We can't just start using a metal pep side, orally in dogs, on a regular basis.

Michael Dryden: It's the last until mythic on the planet In these madrs. It's the last antimic. I know repeat myself on the planet that works in these dogs. We can't lose it. We can't. Okay. So we've got to dotted our eyes crossed our T's make sure everything else has failed us. That's where I went through everything. After this point about the life cycle reinfections infection Coprophagee all that stuff. We got to make sure. this is a last resort. Okay, so what they do is you take the Topical cat product and we're dosing it in one big per keg orally in a dog. Again, it's not approved. This is a last resort.

Michael Dryden: The other thing, you remember, these dogs cannot have heartworm and circulating, Michael Floria. This is a very potent, Michael Flareside into kill these dogs. So you've got to make sure these dogs don't have heartworm a certainly, Michael Flurry. It also has to be used with caution if at all in dogs, we suspect might have an Avery mcnocent sensitivity that MDR one gene, deletion issue dogs, that have problems with high dose of ivermectin, Because this drug works very similar in that regard, and that's So, a couple big cautionary notes here, so, topical cap, profender Regardless of this of the size of the product contains 21 point four milligrams per ml. So, what you do is you take the weight of the dog and kilograms

Michael Dryden: Multiply by one. Okay, the semantics here, divided by 21.4 and that gives you the amount of you ministered to that, dog of that oral product orally. So if I got a 20 kilogram dog, Divide that by 21.4 milligrams per kilogram body weight. That means of that cat product. I'm given that 20 kilogram dog less than an I'm giving it 0.94, MLS tuberculin syringe. You're going to. Accurately doses in these dogs. So you're gonna get less than an ML and a 20 kilogram dog? Again, This has been published this show that it works in. These ones that are Resisted, all three classes of product out there and again, there's a couple publications out there now on this but be careful. Last resort, please. And of course, the other issue we face when it comes to hookworms.

Michael Dryden: There's zoonotic that they could talk cause continuous over my grants. That's a major problem. The creeping eruptions in humans. Particularly in beach areas though, quite frankly, most of the issues we face down in Florida, beaches are probably Brazilian and not Caninem based on that all the feral cats down their defeating on the beaches until that. That's been really fairly well. Documented and Brazilians, 18, worst, lesions, and canine of does, but again, it's still a significant candle containers over my Antelope Caninem as well. Brazilian CNC can actually in some people get to the longs and kind cause a pneumonitis and very rarely they've made it back into the small intestine And if I can write us,'t Humans have their own hookworms, so these didn't mature in people, but the immature larva caused a problem.

00:50:00

Michael Dryden: There's a lot of references out there. All this stuff is documented, all these references are there. You can pull them up. You look at them yourself. But remember if we get to the issue there at the end where we think we got to use a middle peptide I always recommend you contact a veterologist to walk you through this scenario. I hope this has been beneficial I appreciate the opportunity to present this to you again. I'll thank you very, very much.

Melissa Schalles: Dr. Dryden, thank you so very much. We appreciate it.

Michael Dryden: You're welcome.

Meeting ended after 00:50:53 👋