Wormsheild from Banfield

[MaryP]

I received an application for a foster dog and they listed Hannah Worm Sheild as their hw preventative. It is Banfield's brand of hw preventative and it includes pyrantel in addition to ivermectin. Is there any concern about giving pyrantel on a regular (monthly) basis long-term? It seems overkill to me.

[Maralynn]

I received an application for a foster dog and they listed Hannah Worm Sheild as their hw preventative. It is Banfield's brand of hw preventative and it includes pyrantel in addition to ivermectin. Is there any concern about giving pyrantel on a regular (monthly) basis long-term? It seems overkill to me.

 

Those are the same active ingredients that are in Heartgard Plus

[Lenajo]

overuse and underdose - a recipe for parasitic resistance

[PennyT]

overuse and underdose - a recipe for parasitic resistance

 

Absolutely.

 

I am amazed at how long ivermectin based HW drugs worked. Consider the problem, particularly in Texas I hear, with sheep parasite resistance to ivermectin type wormers. Resistant heartworms were a long time coming. My vet here in Poplarville told me the problem is a post Katrina issue, so that opens up avenues of inquiry: 1) overuse and underdosage in New Orleans and the Gulf Coast prodded the evolution of resistance which marched northward with evacuation, an obvious conclusion he did not bother to discuss; 2) some new mosquito carries more HW, a possibility he mentioned that has been discussed; 3) Katrina stirred up things better left alone and long buried. 3 is a science fiction notion of mine, more likely to be a reality in terms of cancer producing agents than for heartworms.

 

Penny

[Lenajo]

they don't make brand Filarabits anymore, but the generic is still out there. While it's more annoying (must be given daily, no missing, and it cannot be used on hw+ dogs) it is a totally different chemical that has not in my reading been recorded as being ineffective.

 

Are any of these dogs coming up positive on Intraceptor?

[MaryP]

Those are the same active ingredients that are in Heartgard Plus

 

Oh, I didn't realize that. I don't use Heartgard, but I guess I could have taken a moment to look up the ingredients of HG, since I was told that WS is like a generic HG (though I hear it costs the same ). Seems silly to me to worm a dog every month without cause, though.

 

It's certainly scary to think that hw's may be becoming resistant to Ivermectin. Time to leave the south!

[Mark Billadeau]

Unless you have evidence that HWs are becoming resistant to HW preventatives, PLEASE, don't imply it. That is how internet roomers get started and many people will believe what they read on the internet (for example: Border Collies are sensitive to ivermectin).

 

If you have evidence that HW are becoming resistant to preventatives please provided it for all to read.

 

Mark

[PennyT]

Mark, you think the drug manufacturers are paying for treatment on the basis of a rumor?

 

I took the time out from my busy life to provide you with information. I don't care if you believe it.

 

It strikes me as very odd that you accuse me of rumor mongering without at least googling heartworm resistance dog or some similar combination yourself.

[Mark Billadeau]

Reports of Lack of Efficacy

Lack of efficacy (LOE) of a heartworm preventive product is defined by the Center for Veterinary Medicine of the Food and Drug Administration (FDA) in the USA as a dog testing heartworm positive while consistently receiving heartworm prevention. There are many possible reasons for reports of LOE, including failure to administer sufficient preventive, failure to administer the preventive at the appropriate time interval, failure of a dog to retain a dose and failure of absorption of active ingredient. There is also biological variation in how hosts within the same species metabolize a drug as well as how parasites respond to a drug. Thus, the exact cause of a reported LOE of a product is extremely difficult to determine.

 

Most LOE claims can be explained by compliance issues, either between the clinic and the client or the client and the pet. It is possible for an animal to become infected by missing or receiving a delayed administration of just one dose of a heartworm preventive product. The likelihood of this occurring is increased in endemic areas where infection challenges are exceptionally high when compared with other sections of the USA. Highly endemic areas typically have warm temperatures most of the year, an abundance of standing water and substantial mosquito populations. Many of these areas also have large populations of wild canids, with most of the animals infected with heartworms providing a large reservoir of infection. In addition, manufacturers have improved the sensitivity of heartworm antigen tests during the past decade and more animals with low female worm burdens are now being detected. The increase in the number of LOE reports to the FDA during the past several years has lead to concerns of possible heartworm resistance to the current heartworm preventives. First, it is important to understand that parasites do not become resistant to drugs, but rather, product use under specific conditions inadvertently selects worms with resistance genes. These populations of surviving worms are called resistant strains. Some conditions are known to favor the selection of resistant strains, as occurs with trichostrongylid nematodes of small ruminants and with horn flies. Limited refugia (i.e., worms with wild-type genes), a direct life cycle, treatment of entire groups of confined individuals, and the presence of heavy parasites burdens reduce the refugia and support the concentration of selected, resistant genes. Thus, the shorter the life cycle of the parasite, the more rapidly the resistant-gene-selection process proceeds. If we examine heartworm infection using the same selection factors, we see a converse scenario. Factors such as a long life cycle, relatively light worm burden, an indirect life cycle with mosquitoes as vectors, a large refugia of infected but untreated pets and wild canids that roam freely throughout their territories, treatment of dogs singly rather than in large groups, and pets that travel widely with their owners do not favor the selection of resistant strains. The epidemiology, treatment patterns and abundance of refugia of parasites such as heartworms ensures the wide distribution of large populations of heartworms that are not under strong selection pressure, and their wild-type genes serve to dilute any resistance genes that exist in geographically different worm populations. These conditions greatly decrease the likelihood of widespread emergence of resistant heartworm strains and any resistant strain would likely remain localized. Professional and client education are perhaps the most important factors to consider in addressing the reports of apparent lack of efficacy of preventive products. The complex biology of the parasite, the effect of changing environmental conditions that affect vector populations, the dynamics of host (wild and domestic) populations, and even the dynamics of human interactions with their pets are also relevant. In the face of the many variable factors, it is critical that veterinary practices ensure that clients understand the risk of heartworm infection in their area and provide their pets with appropriate heartworm prevention, i.e., consistent year-round administration of preventives.

 

Source: American Heartworm Society

 

Battle Against Heartworms Getting Tougher!

 

Every month, lots of dog owners, and a few cat owners, give their pets some form of heartworm prevention. But recent studies are showing increasing numbers of heartworm positive pets across the country. Some people believe the worms now have the upper hand. Has our trusted protection failed us?

 

By: Dr. Jim Humphries, Veterinary News Network

 

Dog owners, and a growing number of cat owners understand that once -a-month heartworm preventives keep their pets safe from a very serious cardiovascular parasitic disease. Despite consistent use of preventive medications, a significant number of dogs are testing positive for heartworms, especially in the mosquito heavy Southeastern US. Are we seeing the beginnings of a resistance movement?

 

In some cases, careful questioning of the clients reveals some monthly doses of medication were not given, opening the door for potential infection. In other cases, medical records and client compliance appear to be complete, yet the pet is positive on the annual heartworm blood test.

 

Heartworm preventive works by killing immature heartworm larvae that are spread by mosquitoes. In theory, a pet who receives medication each month should be protected and never have a positive heartworm test. Why then, do some dogs test positive?

 

Many owners are quick to blame the heartworm preventives. They believe continued use of the drugs will create resistant worms and that will lead to an increase in positive cases. On the surface, this theory appears to have merit. After all, we know that improper and excessive use of antibiotics can create resistant bacteria.

 

But according to an article in Veterinary Parasitology, heartworm resistance should not occur. The authors looked at the life cycle of the heartworm, genetic mechanisms of resistance as well as the timing and dose of the heartworm medications. Their conclusion shows the current medications are unlikely to select for any sort of genetic resistance among the heartworm parasite. In other words, it is doubtful current heartworm preventive practices are causing any resistance. So, what is happening with these heartworm positive dogs?

 

As unpopular as it sounds, pet owners and veterinarians may have to share the blame. A pet owner who fails to purchase enough preventative medication is putting their pet at risk. Also, research shows that nearly 50% of dog owners who buy heartworm prevention do not give the medication as directed.

......

 

Is anthelmintic resistance a concern for heartworm control?

 

6. Conclusions

 

Anthelmintic resistance is already a severe problem in some trichostrongylid nematodes of ruminants and small strongyles of horses. The global and regional control programs for human filarial nematode parasites are likely to impose significant selection pressure for anthelmintic resistance to develop, and already there are a few reports of sub-optimal responses and genetic changes consistent with resistance being selected. However, in non-filarial nematode parasites in humans, selection for anthelmintic resistance is likely to be peak unless chemotherapeutic control is intensified. Because of certain factors (i.e., the extent of refugia, treatment coverage, the low drug dosage rate used, the number of genes involved, and the complexity of the resistance mechanism(s) to avermectin/milbemycin anthelmintics), which are important for resistance selection, the selection for resistance in D. immitis is likely to be very low, and a resistance problem is not likely to occur with current heartworm control practices.

[juliepoudrier]

Without Googling either, ISTM that HW preventive manufacturers have *always* provided treatment for HW+ dogs when it could be proven that the dogs had been given HW preventive as prescribed (at least it was the case back when I was working for a vet in the mid- to late-80s). So the question is whether the number of dogs they've had to pay to treat has increased. Another thing I'd be curious to know is whether HW infection is on the increase in general among all dogs, treated or not.

 

I also think it would be interesting to find out if climate trends have had an impact on increased spread of HW (if, for example, you must have at least three nights in a row where the temps are 54 or higher--or whatever that magic number is--for mosquitoes to be able to spread HW is that then also a factor in observed increases in infection?).

 

ETA It would appear that Mark has found references that at least answer the resistance issue.

 

FWIW, I know there are plenty of people who stretch treatments out to the 45-day mark, but it might make sense to back that off by a few days, say, 40 days, just to be safe.

 

J.

[Mark Billadeau]

There you go Penny.

 

BTW Manufacturers pay to have problems go away since they know hat bad press impacts profit. It's easier (and better for their image) to pay for the treatment than to prove the ower did not make sure the dog recieved and retained the correct dose.

 

....research shows that nearly 50% of dog owners who buy heartworm prevention do not give the medication as directed.

[juliepoudrier]

Penny,

On your list, I think #1 is certainly plausible, though I would say that it was a direct result of Katrina because there was lots of standing water, warm temps, and of course lots of abandoned/lost animals who obviously weren't receiving preventive, so a classic example of how lack of preventive can allow something like HW to explode in a certain population. I don't know that evacuated animals carried a "super heartworm" north, but simply may have just carried HW, and if the animal's origin wasn't identified at the time it was found to be HW positive, it might then appear that a resistant strain is moving north when in fact it's just the same old HW in animals who were not treated with preventive for some period of time.

 

J.

[Mark Billadeau]

Here is an article which may give a reason for the appearent resistance of heartworms to the "preventatives".

 

The safety-net story about macrocyclic lactone heartworm preventives: A review, an update, and recommendations

 

Veterinary Parasitology

Volume 133, Issues 2-3, 24 October 2005, Pages 197-206

John W. McCall

Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA

 

Abstract

A number of safe, effective, and convenient heartworm preventatives are currently available for virtually all canine and feline pets. Yet, a 2001 survey of over 18,000 veterinary clinics in the United States identified more than 240,000 dogs and 3000 cats infected with Dirofilaria immitis. This high level of owner compliance failure is alarming. Prolonged administration of some of the macrocyclic lactone (ML) preventatives kills young larvae, older larvae, “immatures,” young adults, and/or old adults. Efficacy of 95% or more requires dosing for 9–30 months, with older worms being more difficult to kill. Of the various MLs, ivermectin (IVM) has the most potent safety-net and adulticidal activity, milbemycin oxime has the least, and selamectin and moxidectin injectable lie somewhere in between. The unique effects of IVM are related to the age of the heartworms at initiation of treatment. The earlier treatment is started, the more stunted and smaller the worms and the shorter their survival time. Conversely, the later treatment is started, the longer the worms live, and the more likely the dog will be antigen- and microfilariae-positive. Drug effects do not appear to be enhanced by increasing the dosage or administering at shorter intervals, and it appears that continuous monthly treatment is needed to produce the full effects of the drug. The American Heartworm Society (AHS) recognizes the safety-net (or reach-back effect) and adulticidal properties of some MLs, particularly IVM. The AHS 2003 (American Heartworm Society, 2004. 2003 Updated guidelines for the diagnosis, prevention, and management of heartworm (Dirofilaria immitis) infection in dogs. In: McCall, et al., (Eds.), Proceedings of the Symposium Session on Recent Advances in Heartworm Disease, The 19th International Conference of the World Association for the Advancement of Veterinary Parasitology, New Orleans, LA, 10–14 August, 2003. Vet. Parasitol. 125, 105–130) canine guidelines state that it is beneficial to administer prophylactic doses of IVM before treatment with melarsomine. Results of laboratory studies suggest that less active dogs are at low risk of severe thromboembolism and death. However, heartworm-positive working dogs might be more at risk. Worsened radiographic and echocardiographic images in a client-owned dog given IVM monthly for 2 years with greatly restricted exercise suggests that such treatment of dogs with clinical, radiographic, and/or echocardiographic evidence of heartworm disease as well as for asymptomatic working dogs is contraindicated. Furthermore, until further data are available, such treatment of even the less active asymptomatic dog should be administered only with much caution and with examination by a veterinarian at least once every 4–6 months. IVM clearly provides potent “safety-net” activity against older larvae, immatures, and young adults in cases of owner compliance failure, even when the owner and veterinarian are not aware that the animal is infected, and offers much promise as a unique “soft-kill” treatment for young, and possibly older adult heartworms, with reduced risks.

 

I have highlighted the statement that caught me eye. All the heartworm "preventatives" are macrocyclic lactones, each has slightly different efficacy against adult worms. If the heartworms are allowed to mature (missed a dose, dose not given on time, dog does not retain dose, etc) then, the newer heartworm preventatives will not offer as much protection against maturing HW infestation as the older preventative.

[PennyT]

Unless I identified a theory as my own, I was reporting what my vet told me, and I really don't have to time right now to log into my Tulane account and search their electronic holdings.

 

Here is another bit of information from him that I left out the first time. A single, large practice north of here reported that among the heartworm positive dogs tested in the last year 35 were on heartworm treatment and could prove it with records. That is a huge number. It's really easy to blame myself (and I do not discount the possibility, BTW) because I am one fallible person. It's not so easy to dismiss numbers like that.

 

The vet also said that using a different product in the Avermectin family every two weeks is not preventing infestation. I will ask him where the information came from because I have to call this morning.

 

Penny

[Mark Billadeau]

I've been searching (google scholar) for articles on HW resistance to macrocyclic lactones and have found no publications (either it's too early in the discovery or resistance has not been demonstrated).

 

I have seen studies that looked at the "doubling up" protocol and found it no more effective than the monthly protocol.

 

I have seen several articles suggest that the dose (while given by the owner) may not have been retained by the dog long enough for adsorption yielding the dose ineffective. In highly endemic areas, it has been suggested that missing any dose or being late on any dose may be sufficient to allow the infestation to mature; the preventatives are less effective against a mature infestation (and there are differences in efficacy against mature infestations between the various preventatives). Note that while they are sold as preventatives, in fact these drugs are simply killing off the infestation before it matures past a certain stage of the lifecycle. The dosing period was designed to match this lifecycle.

[juliepoudrier]

Mark,

In your opinion, would this mean that people should stick to the once-a-month dose vs. stretching it out to 40-45 days? That's what I'm gathering from this information.

 

I am certainly guilty of not giving my dogs their HW preventive *exactly* every 30 days. I thought I had a 10-day window to play with, but maybe that's not really the case (that is, the further back the infestation, the less likely the preventive is to kill of the HW).

 

J.

[Maralynn]

....research shows that nearly 50% of dog owners who buy heartworm prevention do not give the medication as directed

 

Very true and a significant factor. But this still does not answer the question why dogs that are dosed properly and retain those doses get HW while on a preventative. While it may be the fault of owners in many cases, it also happens when the owner does everything right. And there is enough of an issue that vets in certain areas are telling clients to dose every 15 days with different treatments. If not drug resistance, what? Are they getting bit by so many mosquitoes with HW that it is overloading them? People owning high value working and sporting dogs tend to be very proactive and conscientious in caring for them. Yet some of these dogs are still showing up HW+ despite regular testing and the use of preventatives.

 

This study recognizes the problem, and notes that a heavy exposure to infected mosquitoes may be one contributing cause to the increase of cases in the Mississippi delta area.

http://www.stlouisvma.org/downloads/Dryden...009%20notes.pdf

 

While not a scientific article, this might be of interest

Latest news on the heartworm epidemic

[Liz P]

Mark,

In your opinion, would this mean that people should stick to the once-a-month dose vs. stretching it out to 40-45 days? That's what I'm gathering from this information.

 

J.

 

 

Not Mark, but ABSOLUTELY! I was just at a conference where research was presented that showed that if you expose dogs to heartworm and wait until day 45 to give a dose of HG/Interceptor/etc, one in eight dogs will become infected long term. Another study showed that only about 80% of the microfilaria will be killed off when exposed to the drugs on day 45.

 

For the less scientifically inclined, this does not mean that 1 in 8 dogs in the real world who get HG on day 45 will become infected. Pet dogs might not be exposed to heartworms in a particular month. Dogs also demonstrate a limited ability to kill of HWs naturally.

 

Owners may be buying 12 doses of "preventative" a year, but if you forget to give it on the same date every month and are too far between doses you are running the risk of your dog becoming infected.

[Liz P]

Very true and a significant factor. But this still does not answer the question why dogs that are dosed properly and retain those doses get HW while on a preventative.

 

The quotes Mark provided did ansnwer this question. Not all dogs absorb the drug from their GI tract at the same rate. The dogs becoming infected may be absorbing a lower dose. If a dog is sick (ex: diarrhea) the drug may pass through their system too quickly to be absorbed.

 

Not all people/dogs/cats/horses/etc react to the same drug in the same way. Our bodies are different in how we handle drugs.

[Mark Billadeau]

In areas with a very high level of HW it is possible that dogs are becoming infected monthly with a higher load of HWs than what was used by the drug companies to establish the minimum effective doses for each of their preventatives. This is not the same thing as the HWs developing resistance. More frequent dosing may not be effective if each mosquito bite is delivering more L3; since a later second dose will be less effective at killing the more mature HWs (1st dose kills some of the 30 day old HWs, 2nd dose must now kill the remaining 45 day old HWs).

[Maralynn]

In areas with a very high level of HW it is possible that dogs are becoming infected monthly with a higher load of HWs than what was used by the drug companies to establish the minimum effective doses for each of their preventatives. This is not the same thing as the HWs developing resistance. More frequent dosing may not be effective if each mosquito bite is delivering more L3; since a later second dose will be less effective at killing the more mature HWs (1st dose kills some of the 30 day old HWs, 2nd dose must now kill the remaining 45 day old HWs).

 

Thanks - this makes a lot of sense.

[diane allen]

I don't live in an area with high HW infestation, but do travel, so yearly test and give preventative about 8 months of the year, then stop for winter. My vet only carries Heartgard Plus, and I don't want all the extra "junk" that we don't need. I also prefer the tablets vs. the chewables (can you say "artificial flavor?"!). So, my vet kindly writes the paper prescription, and I have mailed it off to a mail order place to fill.

 

I checked with Drs. Foster & Smith - they are allowing only ONE tablet per order, of the 26-50 pound dog size; they said it is being reformulated (or something - the guy didn't sound 100% certain...), and they didn't have the new version, and a limited supply of the old. The Merial website does not have a "contact us" link.

 

Thankfully, I have several tablets left from last year that I can use now. But after reading all this...I wonder if they are reacting to this most recent info. Anybody know, or know where to find out?? (I too have "stretched" the 30 day thing, and thankfully have a few left from last year to get started with, this year...)

[Mark Billadeau]

I am searching for the dose of L3 used to establish the minimum effective dose. I know the study, I'm trying to locate it on-line. Some of you may find this interesting:

NADA 138-412 HEARTGARD-30® - original approval

Approval Date: March 2, 1987

[MaryP]

I checked with Drs. Foster & Smith - they are allowing only ONE tablet per order, of the 26-50 pound dog size; they said it is being reformulated (or something - the guy didn't sound 100% certain...), and they didn't have the new version, and a limited supply of the old. The Merial website does not have a "contact us" link.

 

I know that there was a shortage of Immiticide (also made by Merial) up until recently, so I wondered if the same issue had come up with the HG tablets that you are referring to. I did a little Google search and found this article. This might explain the issue that you are seeing. The Immiticide shortage is apparently over (I've had two dogs treated recently), so hopefully the HG tablet shortage will be over soon, too.

[Maralynn]

I am searching for the dose of L3 used to establish the minimum effective dose. I know the study, I'm trying to locate it on-line. Some of you may find this interesting:

NADA 138-412 HEARTGARD-30® - original approval

Approval Date: March 2, 1987

 

So, if I'm understanding this all correctly, theoretically all that would be needed to control HW in dogs in high load areas would be a higher dose or more frequent dosing?