Fighting Resistant Hookworms: Inside the AAVP Task Force's New Diagnosis and Treatment Guidelines

Hookworm cases that “just won’t clear” are no longer a weird outlier, and that should change how we practice. We sit down with parasitology expert Dr. Ray Kaplan to unpack the American Association of Veterinary Parasitologists (AAVP) Hookworm Task Force recommendations on diagnosing and treating multidrug-resistant canine hookworms, including what clinics can do right now to stop guessing and start confirming.

We talk through how this problem came to light, why drug-resistant hookworms likely gained traction in greyhound breeding and racing environments, and why it’s now a pet dog problem across breeds and regions. We also zoom out to the biology that makes Ancylostoma caninum such a persistent threat, from multiple routes of infection to the possibility of “larva leak,” and then get practical about what should raise suspicion. 

From there, we map out a clear diagnostic path. We discuss the value of a two-week post-treatment fecal recheck, how to use a fecal egg count reduction test to quantify efficacy, and what “good” reduction should look like. We cover the task force approach to treatment and testing across the three drug classes (topical moxidectin, pyrantel, and benzimidazoles like fenbendazole or febantel), the limits of current PCR testing, and when extra-label emodepside enters the conversation with important safety precautions. If you want a grounded, clinic-ready framework that also addresses environmental contamination and zoonotic risk, this one’s for you. 

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Transcript

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Welcome And Why This Review Matters

Lisa Fortier 0:32

Welcome to Epic Award-winning Veterinary Vertex, the AMA journal's podcast where we delve into behind-the-scenes look with manuscript authors. I'm editor-in-chief Lisa Fortier, joined by Associate Editor Sarah Wright. Today we're discussing the American Association of Veterinary Parasitologists, or the AAVP Hookworm Task Force review on best practices for diagnosis and treatment of multidrug-resistant hookworms with our guest, Ray Kaplan. Thank you for joining us, Ray.

Ray Kaplan 1:01

Thank you for having me.

Lisa Fortier 1:02

All right, Ray, to

How The Task Force Began

Lisa Fortier 1:03

get started. Uh, what prompted the AAVP to establish this hookworm task force in around, I think, 2021?

Ray Kaplan 1:10

Yeah, so uh back around nine, uh about 2017, um, I became aware from some communications with colleagues that there seemed to be cases uh of hookworms that weren't that weren't um uh able to be uh treated. Um so I um being an expert in drug resistance and parasites, but for primarily most of my focus in my career has been on large animal parasites, where drug resistance is known to be a problem for a long time, um, I decided to just take a look and see if there's something there. Um I put on, uh I had a new uh new PhD student uh and uh we agreed he would he would pursue that, uh, Dr. Pablo Jimenez uh Castro. Um and so it just led us on this um grand uh uh you know you know bit of work uh and over a few years. And the more we delved into it, the more we the more we were finding this was a pretty big problem. Um and so we first we first published a paper uh after having uh clearly establishing uh using molecular um in vitro and in vivo um testing that we had multiple drug resistance um in uh in hookworms. And then from there we you know we did further studies and kept further characterizing the problem. Um and eventually that culminated in doing a national survey um with the assistance uh of IDEX, who provided us uh samples from four regional labs. And and so that we went up testing 685 samples um using uh um uh a sequence, DNA sequencing uh method, um, and uh just found that the resistance problem was really widespread around the country uh at pretty high levels. Um and so once once we had that information and we presented it at the AAVP meeting, um uh had some discussions with AAVP leadership, uh, and it was decided that this is this is uh something that really needs uh the attention of AAVP. Uh and so that task force was formed uh to try to develop some um some unified uh recommendations uh for how veterinarians can can understand and manage the problem.

Why Hookworms Still Threaten Dogs

Sarah Wright 3:32

Ray, for listeners who may not deal with parasitology every day, why are hookworms such an important parasite in canine medicine?

Ray Kaplan 3:39

Uh that's a good question. I mean, years ago, hookworms were extremely prevalent in dogs. Uh, depending upon the study, it varied from you know, 10 to up to 50% of dogs were infected with hookworms. Uh, you know, that was, you know, many decades ago. Um, but with um better nutrition, uh more awareness of fecal hygiene, um, and and then all of the great uh anthematic drugs um that we have, and including all dogs that are on uh monthly heart hormor-flee um prevention, uh, are getting medications that also um uh kill internal internal parasites uh such as hookworms. Um so the prevalence of hookworms fell dramatically um over several decades. Um but even today it's still the most prevalent um intestinal um helmet of dogs. And it is highly pathogenic. Um and it's very successful parasite because it can infect dogs in multiple routes uh um orally um or percutaneously. Um it can be uh can be transmitted to puppies through the milk after they're born. And so it's it's a very clever parasite. Um so it's transmitted in a number of ways that make it make it quite successful. And it's highly pathogenic. It's uh it's it feeds on blood and uh and it can cause severe anemia and in dogs and potentially death in in cases where there's a very heavy infection.

How Resistance Emerged And Spread

Lisa Fortier 5:11

Yeah, all good reminders. It's been a long time since I thought about hookworms in dogs as an equine practitioner. Still a problem, but um, I thought really interesting, Ray, was that uh the evidence in your article suggested that hookworms originated in greyhound breeding in racing environments. How did you figure that out and how did it spread beyond that population?

Ray Kaplan 5:32

Well, that would be the the the drug-resistant hookworms. Yes. Yes. Um well um it it came about mostly because most of the c early cases um that were being done that were being diagnosed uh were in greyhounds. And and um greyhounds seemed to be heavily infected with with hookworms, and and then when we would test them, they were um at resistant at very, very high levels. Um and so it appeared that um it's likely originated in greyhounds, but but that's not real evidence. But when we started doing um some of the um uh DNA sequencing, um then we started getting genetic evidence. And the um the genetic backgrounds of the worms uh that we were seeing the resistance on um was was with that we saw in pets was the same one we saw in greyhounds, but at much, much higher level in greyhounds. Um and so it really pointed to um that that the the that the mutations uh uh first appeared um on greyhound breeding farms and kennels, um, and then from there spread to the dog population. Um so the we don't the evidence is not yet definitive, but it's it's pretty strong that that this is what happened. And um and greyhounds, you know, the the way they're raised, um um, they they they for years they were uh viewwormed at extremely frequent intervals, uh and they uh they they were exercised in sand uh areas of sand, um uh which is an ideal trans transmitter uh uh for uh for hookworms. So um so it appears that you know that in their attempt to limit the effects of hookworms on the greyhounds is that they selected for multiple drug-resistant uh hookworms. And then as those uh greyhounds uh were adopted out um and and homed, um they then spread those worms um into the general pet population.

Sarah Wright 7:40

That is fascinating and also very scary. I don't know how I feel about that.

Ray Kaplan 7:44

One thing I'd like to add, though, is that it's really important uh for everyone, including veterinarians and and and dog owners, to understand as well, though, that this is no longer a greyhound problem. There aren't that many greyhounds left racing. Greyhound racing is pretty much almost eliminated. West Virginia is the only state left that that has illegal greyhound racing. So there's really not many greyhounds. Uh and and whatever the few of the there, probably the the the industry is on its last legs. Um this is a this is a a dog problem, a pet dog problem. And um uh and it's spread, we see it in every single breed, um uh every every part of the country. Uh so this is it's you know, the greyhounds are still probably more likely um to have the problem, um, but uh especially if they're more recently coming off the track uh or or off the breeding farm, but it's a problem across uh all breeds and and types of dogs um throughout the U.S.

Sarah Wright 8:47

That's a

The Biggest Misconception In Practice

Sarah Wright 8:48

great clarification. Actually, a great segue too to our next question. What are some of the biggest misconceptions veterinarians may still have about drug-resistant hookworms?

Ray Kaplan 8:57

I I think the misconception is the same one I saw with large animal parasites, um, is that um they they they they accept that it's an issue, but it's uh not an issue in their practice. It's somebody else's. It's like we saw we saw farms where we were seeing high prevalence of resistance uh on farms, meaning this such to a point that almost every farm we knew had drug-resistant worms, but farmers still thought it was their neighbor's issue and not theirs, um, and because because nobody was really doing any testing. Um it's the same thing that I think happened uh in with small animal medicine. Um, you know, veterinarians would would um treat dogs for hookworms, uh send them home, just assume the treatment worked, um, and no follow-up was really done. And I don't, I I still don't think there's a lot of follow-up that's being done yet. And so um, you know, dogs, most adult dogs, you know, have fairly good immunity to hookworms. Um, so if they have them, um, they're probably at a low level in most cases, um, and they're not going to be causing uh severe disease in most cases. So um I think I think most veterinarians are are not aware of how prevalent this problem really is, uh, and that the they need to be more aware of it and do more testing and surveillance uh to detect

Red Flags And The Right Follow-Up

Ray Kaplan 10:20

it.

Lisa Fortier 10:20

Although on that line, Ray, what clues should alert a veterinarian that they might be dealing with a drug-resistant case rather than a treatment failure or reinfection?

Ray Kaplan 10:29

It's a good question because it because the answer to that question would have been different, you know, 10 years ago. Um, because hookworms are known to have this complex biology where where larvae that penetrate uh through the skin of mature dogs will go into the somatic tissues uh and in some cases then can leak out, something called larva leak. It's a well, you know, well-described phenomena. Although it's not well understood, it's well described. And at first, even in these greyhound dogs, most peristologists that were dealing with them, because again, I was, you know, my focus in peristology was more on the large animal side. Um, and so but the people the veterinarians on the swamp side that were dealing with some of these cases and the greyhounds, they were assuming that this was larva leak at first, because that is that is uh known. So, and then of course there's always reinfection as well. The bottom line is that those things can happen, but given what we know now about the prevalence and distribution of these multiple drug reduced and hookworms, that those are much less likely than resistance to explain a dog that's that has uh chronic hookworm infection. Um, so if a dog is on any type of heartworm um uh preventive, a monthly preventive, they shouldn't have any hookworms. Um, if they do, that's gonna be uh uh a red flag for uh likely resistance. Um also dogs that kind of come into the clinic with hookworms that maybe aren't on uh you know monthly um gearworm treatment, you know the veterinari should be suspicious of any case, really at this point in time that it is resistant. It may or may not be, but um but the prudent thing to do uh it would be to um actually once you have a worm-positive case and you treat it, that you do a follow-up fecal uh two weeks later. Um and all these drugs originally when they were first uh uh marketed, all had virtually almost 100% efficacy in reducing egg counts. Uh against the worms, it's more like 99% efficacy, but in terms of reducing egg counts, it's virtually it was virtually 100%. Uh unless the unless the the dog had a huge, very high egg count, um, they should go to zero or near zero. And so on a on a flotation, you shouldn't see you shouldn't see any eggs post-treatment or very few eggs. Um and uh so just doing that simple thing um can can can can help a veterinarian uh determine whether they need to be more suspicious of resistance. If they are suspicious of resistance, then they should they'll need to do actually a diagnostic, which would involve what's called a fecal egg count reduction test, um, where you um do an actual fecal egg count, like we do in sheep before the treatment and then two weeks after treatment and calculate uh what the reduction in egg counts were. Again, that we should see um very high reductions in egg counts. And whether we use one drug or multiple drugs to treat will determine what efficacy we should expect, but we should expect high efficacy with these drugs. Um, and if we don't see high efficacy, then that's strong evidence uh that we have a resistance case.

Triple-Drug Testing And Treatment Paths

Sarah Wright 13:52

Once resistance is suspected or confirmed, what are the key treatment and management recommendations from the task force?

Ray Kaplan 13:58

Okay, so as far as for treating um drug resistant hookworms, um one thing uh um to keep in mind is that resistance is not all or nothing. Um it's uh worms can become more and more resistant over time. Um and of course, there's multiple drugs. And so uh some of these worms that we're seeing um are resistant to every drug that we that's labeled for use to treat hookworms. But in some cases, um the worms may be still susceptible to one or two of the drugs and only resistant to maybe one drug. Um there's no way of knowing um and uh without actually testing um the dogs. And um so so how so if if if um treatment failure is suspected due to one drug, it becomes complicated to and expensive as to try to test every single drug separately. So what we recommend in the task force is that once there's uh evidence that there's drug resistance, um, that um a fecal account reduction test be performed using drugs of all three classes, uh which include topical moxidectin, uh, pyrantel, and then either fenbenazole or feventel of the benzymidazole class. Treat with all three drugs, um, and then measure the percent reduction. Uh it should be the egg counts should be reduced by greater than 98%. Um if they're not, then that's suggestive of multiple resistance to all three classes of drugs, which is a big problem then, because those are the those are all the classes of drugs that are that are labeled for treatment of folk worms. Um in um if if so if multiple drug resistance to all the drug classes is then confirmed, uh, then the only available treatment we we have right now we can recommend is treatment with hemodepside, which is uh a drug uh uh label for cats. Um it's a topical um uh formulation for cats. And um and so it's it's an extra so it's extra label use for dogs, but there's a lot of caveats for using it um um in in in dogs, because due to the nature of being an extra label drug, and and it's um it's safe, the drug is quite safe um when when dosed correctly, um, but there is there is potential for toxicity and other side effects from that drug. Um so there's uh so there's a list of precautions uh that the task force has written has listed in the paper of veterinarians that they're gonna use emodepside um uh to be aware of. And and we strongly recommend that emodepside only be used um after first confirming that using uh the triple combination uh will not will not be successful in eliminating the the infections. The one other the one um sorry, the one one other um um area of diagnostics that I need to mention is that uh there's also um uh a PCR test. Um it's part of the key um key screen from from um antec. And that that test will will test for resistance to just one drug class, the benzemizole class. That's the only class where we have um knowledge of the mutations. Uh it's only it's the only drug test where we have knowledge of the mutations that cause resistance. So those that's where we can actually do the genetic testing for that drug. Um and the the test, uh the PCR test can determine if the mutations for benzene resistant are present. However, that test doesn't measure the level of those mutations. Um and so the mutations might be present at a low level where the drugs still could be effective, or they could be present at a high level where the drugs will be completely ineffective. You can't tell that with the PCR test. All you can tell is if is if that dog's hookworms possess the mutation for benzenazole resistance, but it doesn't also tell you anything about resistance to pyrental or resistance to the um mexicaclactone drugs. So it has its limitations, but in our experience, it seems that we're not saying we in in the in the research we did, we didn't find dogs that only had benzenazole resistance. Most of the dogs had um resistance to all three classes, um, most of the time. The one exception in terms of the profile of resistance was that moxidectin um uh when given as a topical formulation, it's a very high dose of moxidectin, much, much higher than the uh than than the than the dose levels that are included in the monthly preventives, or all monthly preventives. Um and and uh we found that that some of the worms um were still in some cases moxidectin, topcom oxidextin was still quite effective. Um so that's kind of like the last the last uh drug uh standing in a sense. Um so if uh so you might have you could have resistance to the other drugs, because um clearly resistance to pyrotentella medzimizoles, um the evidence suggests that those occurred first. Um and moxidectin was kind of the last the last drug that finally to finally go. So if moxidectin um it may work, um and that's why it's important to test that triple combination. Um if moxidectin doesn't work, then you're you're you're only left with the medopside.

The One Takeaway And Zoonotic Risk

Lisa Fortier 19:46

So many uh good points, Ray, from you and the task force uh and throughout this episode. And if you could distill, if you had one thing that you wanted the veterinarian to remember, just one thing that you want veterinarians to remember about drug-resistant canine hookworms, what would it be?

Ray Kaplan 20:02

Um It would be that they're present uh in your practice area and that you need to be changing your approach on how you diagnose and manage hookworms, and that doing um, you know, testing for every time you see diagnose a case of hookworms, you should be testing to determine if they are resistant. Um, sending the dog home on medication um and then telling him to come back in a year is is really not an appropriate response anymore. You really need to test to see if those hookworms are resistant. Um, because if they are, then um the dog will will contaminate the environment, reinfect itself, potentially reinfect other dogs, uh, as well as the fact that uh that that um slosmicinum is zoonotic. So there is, there is a zoonotic risk as well. So there's you know quite a few reasons why it's really important to make sure that in cases, any hookworm-positive cases that you're dealing with, that the treatment you administer is fully effective. And if it's not fully effective, then you have to do the follow-up testing um and uh and appropriate treatment uh to make sure that you eliminate that infection from that dog.

Sarah Wright 21:18

Ray, thank you so much for joining us today. We appreciate it.

Ray Kaplan 21:21

Oh, for sure. Thank you so much for having me.

Where To Read More And Closing

Sarah Wright 21:24

For our listeners and viewers, you can read Ray's article in JAVMA. I'm Sarah Wright with Lisa Fortier. Be sure to tune in next week for another episode of Veterinary Vertex. And don't forget to leave us a rating review on Apple Podcasts or wherever you listen.