What’s New In Heartworm Prevention, Diagnosis And Treatment in 2017 ?
 
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In Ferrets
 

Ron Hines DVM PhD ...........................

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More on HWD in ferrets

Has My Dog’s Risk Of Catching Heartworms Changed In The Last 8-10 years ?

That depends on you and your pet’s lifestyle and where you live, In the last 8 years I believe that it has remained about the same. The cost of preventatives have come down, urbanization, pet owner education and standards of living have increased. But during the same period, changes in rainfall patterns and a warmer climate have allowed the heartworm parasite to extend its range.

I wrote my website’s base articles on heartworms some years ago. Heartworms are as formidable a disease now as they were then. Over those years, they have steadily spread their range in the United States. They are now present (at least spottily) in dogs in all 48 states. (ref1, ref2, ref3, ref4) Bowman2016b.pdf Ray2010.pdf In Europe, they gradually moved northward. (ref) Morchon2012.pdf In Australia, they have gradually appeared inland from the subtropical coastal. In the United States, areas of heavy infection mirror the areas where the 16 common species of mosquitoes that transmit heartworm larva are found. Those are areas with mild winters, high humidity, lots of rainfall and water impoundments. An unusually cold winter or period of drought is often followed by a temporary drop in the number of heartworm cases veterinarians see. But other factors come into play too. Urban areas with high incomes often have fewer cases than poorer economic areas – probably due to better mosquito control as well as a more informed citizenry able and willing to give their pets monthly heartworm preventatives. (ref) Ledesma2011.pdf

Some folks associate the enlarging areas of heartworm disease with climate change (heartworm larvae do not become infectious in mosquitoes at temperatures below 57F=14C [ref]). But others suggest that it is due to a greater willingness of pet owners to agree to test their dogs for heartworms as well as newer tests that are much more reliable than they once were. Both are plausible; I cannot tell you that they are true.

Has My Cat’s Risk of Catching Heartworms Changed ?

Whenever the chances of dogs in your area catching heartworms goes up or down, the chances of cats in the area becoming infected change accordingly. Parasites periodically mutate and adapt to a new host. So one cannot guarantee that cats will remain a second-best host for heartworms forever. (ref) Levy2017.pdf

Studies to determine how common heartworm infection in cats is tend to under-discover some infected cats. That’s because the in-office tests we use to detect heartworms are ELISA-based. They look for a specific antigen protein that diffuses out from the reproductive tract of “pregnant” adult female worms. Infected cats rarely have more than a few adult heartworms. If they are all males or still juveniles, the test will be falsely negative. Even one mature female worm – capable of doing considerable damage - can be missed by the test. (ref) Park2014.pdf Its been estimated that these tests pick up ~89% of infected cats versus 92% of infected dogs (ref) Aron20XX.pdf Others are less optimistic about the test’s value in cats.

But a 2017 study did use these ELISA to looked for antigen evidence IdexxTripleTestSNAPFeline.pdf of heartworm infection in the blood of 34,975 cats. None of the Canadian samples were positive. Cats from 35 American states were positive. The overall prevalence of positive samples in the United States was 0.4%; had not changed much from what it was ten years earlier. (ref) Lorentzen2008reviewed requested checkout says 0.9% As expected, that percent was considerably higher in the southern states where mosquitoes thrive. And three times the average when cats were allowed to go out doors. Only 12.6 percent of the tested cats were receiving monthly heartworm preventative. (ref) Cats with health issues had a higher likelihood of being positive. That could have been due to their leading a more risky lifestyle or due to immunosupression that made it more likely for the heartworm parasite to survive.

When your cat has or is suspected of having heartworms, the most important thing to do iIs probably to place the cat on doxycycline. That is because doxycycline kills Wolbachia and, as you will read below, Wolbachia pipientis is responsible for much of the inflammation that accompanies heartworm disease. Topically applied Advantage Multi for cats is probably also a very good idea – both because it weakens heartworms and because fleas and some of the mosquitoes that transmit heartworms also carry Wolbachia pipientis within their bodies. (ref1, ref2)
We think that Wolbachia enters the heartworm eggs incubating within the mature female heartworm’s uterus to produce already-infected microfilaria. But Wolbachia is a very ingenious bacteria and whether its modes of transfer are plastic remains unknown. (ref) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC308996/ At the least, your cat will be protected from future heartworm infections.

I Read About Drug-Resistant Heartworms - How Common Is That Now ?

In 2011, I told you that there were isolated areas of the USA where some heartworms appeared to have become resistant to ivermectin-based monthly heartworm preventatives like Heartgard®. (ref) heartwormMedResist.htm Researchers now know that a mutation in a specific heartworm gene (the P-glycoprotein gene) appears responsible for that resistance. That mutation causes a decrease in effectiveness of most of the monthly heartworm preventative formulas (monthly ivermectin, milbemycin, selamectin and twice-yearly moxidectin injections [Proheart 6]) (at least against the MP3 and JYD-34 resistant heartworm strain used for testing at Auburn University [ref] Bowman20XX.pdf).

This form of resistance has not been reported outside of the United States yet. Although it is still rare, it usually occurs in dogs living in areas where the rain that falls drains into the Mississippi river. Parasites of all kinds have a tendency to mutate to avoid the effects of products we commonly use to control them. Whether this will continue to occur with dog heartworms remains unknown. But it is not a far fetch concern. Human ivermectin tablets (Mectizan®) do not appear to be as effective in treating the heartworm’s cousin, Onchocerca, in Africa as it once was. (ref1, ref2) Osei-Atweneboana2011.pdf
Turner2015.pdf Farmers also use ivermectin and moxidectin to control intestinal parasites in their cows. And those parasites appear to be becoming resistant to those drugs considerably faster than heartworms in dogs. (ref1, ref2) Geurdena2015.pdf Almeida2013.pdf

The rate at which parasites tend to become resistant to drugs depends on the size of the untreated pool of animals that do not receive the drug. In the case of cattle, there are few that do not receive them. But in dogs and the wild animals that heartworms live in, that pool of untreated animals is very large. That causes the parasite’s mutation to be much slower because there is no pressure on the parasite species to mutate in order to survive.
Besides the strays and pet dogs that receive no preventatives, the untreated pool includes coyotes and fox. Up to 45.65% of adult Florida coyotes were found to have canine heartworms. (ref) Aher2016.pdf

There are veterinarians that theorize that heartworm-positive dogs that are unknowingly placed on monthly preventatives might encourage the problem of resistance. That’s because some of those dogs continue to harbor the heartworm larva (microfilaria) which, over time, have the potential to become resistant. Those monthly doses were designed to work best against the infective third-stage larva (= L3 larva deposited by mosquitoes, not microfilaria waiting for a new mosquito to come along. (ref) Bowman2012.pdf

It is hard for veterinarians to get a good feel for the extent of the resistance problem because we do not have good tests to gauge resistance. (ref1, ref2) Wolstenholme2015.pdf Evans2007.pdf There are folks however who are attempting to develop such tests. (ref)

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The monthly heartworm preventatives that your veterinarian has for sale are very effective - about as effective as human birth control but with less side effects. Giving them to your dog all year long and beginning giving them at 8-9 weeks of age (when the parasite is still in its L4 stage and most susceptible monthly preventatives - see the graph above) is the best way to prevent heartworms or the possibility of resistance. (ref) Atkins2017.pdf

Most veterinarians have had a client or two who swore that their dog could not possibly have heartworms because they know for a fact that it received its preventative medication monthly. Yet their dog tested positive. Many jump to the conclusion that the heartworms in their dog must be ones that are resistant to monthly heartworm preventatives. But when those cases are closely examined, its usually found that it was owner error or misinformation that accounted for the infection. Perhaps it was a shelter dog and the information that it tested heartworm negative was incorrect. Perhaps at the time of the test it had heartworms too immature to be picked up by the test. Perhaps it was an oral medication that the pet later spit out. Perhaps the dose was too small for the dog’s weight. All our lives have periodic stresses - their ups and downs. Perhaps you or your family were distracted for a time by urgent matters. Compliance with anything as boring as a monthly pill or topical drops is rarely 100% year after year. And it only takes a small window of opportunity for heartworms to sneak in.

The risk increases substantially if you scrimp and only give preventatives during the “mosquito season”. Sure, the odds will be quite high that you dog will not catch heartworms. But why play the odds? The yearly antigen test is not that expensive - particularly if you shop around.

Are Snap Heartworm Tests Always Accurate And Are There Ways To Make Them More Accurate ?

The Idexx Snap® test IdexxSnapTest2014.pdf that veterinarians use is quite accurate in detecting if you dog is infected with heartworms – considerably more so than the earlier tests we had (eg Difil Test) Heartworm-imageDifilITest that just looked for heartworm larva circulating in your pet’s blood. But no test as complex as the Snap® test is free of errors and certain situations trick the test. It looks for tiny protein fragments that mature female heartworms release into your pet’s blood. So dogs with few or no mature female heartworms can give false-negative results. Some of those false-negative dogs had only become infected with male heartworms. In others, the female parasites are not old enough to release these uterine proteins that the test is designed to detect. In still others, the worm’s ability to produce uterine proteins may have been decreased due to prior ivermectin and/or doxycycline administration (ref) Drake2015.pdf There are some vets that believe that extremely heavy burdens of mature female heartworms also occasionally produced negative tests as well (perhaps because their immune system is producing anti-heartworm antibody that ties up the heartworm protein fragments that normally circulate in the pet’s blood stream – but if something like that can actually occurs, it is quite rare). Some consider competitor’s tests less likely to be in error. (ref) Atkins2017.pdf

False positive heartworm tests occasionally occur as well. The Snap test has been designed to be extremely sensitive – it has a “hair trigger”. In most of those false-positive cases, a blood sample sent of to a central commercial or university laboratory comes back negative for heartworms (in the USA Antech or Idexx). Central laboratories almost always confirm a positive initial test with a second more accurate confirmatory test – although that may not be noted on the final report the lab sends to your vet.

Most, but not all, heartworm-infected dogs that are not receiving monthly heartworm preventative medications (now or in the past) have immature heartworm larva circulating in their blood stream. Occasionally (very rarely), your veterinarian will see those larva in the blood of a dog (the old Difil test) link that has had a negative Snap test. There are a few reasons that might occur. Adult heartworms only live a few years (remember, the larval worms need to go through a mosquito before they can become adults). So many vets believe that in those pets, the mature female(s) that gave birth to the larva have already died and the adult’s remnants were absorbed by the pet’s body. There are also a number of worms similar to heartworms that also pass living larva into the blood stream. Some look quite similar to heartworm larva. Most have subtle differences that let experts tell them apart and several veterinary colleges have developed sophisticated tests to identify them. (ref) (Theoretically - but quite unlikely - a transfusion with infected blood might pass dead end heartworm larva to the offspring.)

In my opinion, any dog that has symptoms compatible with heartworm disease and a negative Snap test and any dog that has a positive Snap test and no symptoms or indications of heartworm disease needs a blood sample sent off to a sophisticated central veterinary laboratory for confirmation before contemplating a treatment plan. That is particularly so when the dog’s globulin level Globulin.htm is elevated, ultrasounds (echocardiograms) show suspicious objects or right side, heart flow abnormalities (ref) , X-ray heart and lung pattern changes, the dog is having breathing difficulties, tires easily, is aging rapidly, or has increased inflammatory blood markers. (ref1, ref2) dxme-C-ReactiveProt.htm Mendez2015.pdf That is even more so when the patient is a cat. (ref) Dillon2014.pdf

Heat Treatment Of The Pet’s Blood Sample For A More Sensitive Heartworm Test

For the vast majority of dogs and cats, the in-office Snap test is sufficient. But for Snap-negative dogs with any of the suspicious symptoms I mentioned earlier, and a negative Snap test, something else can be done. A recently study showed that “hidden” heartworm antigen is sometimes liberated by heating the pet’s blood sample prior to running the test. That has been found by some to increase the number of positive cases that are discovered. That is particularly true in cats that rarely have more than one or two adult heartworms (ref) Troyer2014.pdf and in dogs that have produced high levels of anti-heartworm antibodies. That antibody binds to heartworm antigen and can make it invisible to the test. One study also identified another unknown “blocking” agent that caused positive test results to become negative. (ref1, ref2, ref3, ref4) Blagburn2017.pdf Little2014.pdf Little2016.pdf Velasquez2014.pdf The results of a Romanian study (using DiroCHECK®, Zoetis) to discover hidden positive dogs were even more dramatic. (ref) Ciuca2016.pdf

Others dispute the value of heat-treating your pet’s serum prior to running the test. (ref) Nafe2016.pdf But whatever the case, heat treatment has never been reported to produce a false positive. Idexx will run the heat treatment test if your veterinarian requests it. (ref) IdexxHeatTreatment2017.pdf
I do not know of any vets attempting to do serum heat treatments in their office. They send it to a national lab to have that procedure performed (Idexx #7232 @ $30 or $14.95 as add on, Antech # T613 @ $21.20).

Is The FDA-Approved Heartworm Treatment The Best Option For Every Heartworm-Infected Dog ?

No, not always.

For dogs that are still in relatively good health, I still believe that the traditional melarsomine treatment is the best option. There were periods of time when Immiticide®, the Merial melarsomine product was unobtainable. (ref) But since Zoetis entered the market in 2017 with their competitor formulation, Diroban™ Diroban-productInsert that is no longer the case.

But there are situations where neither Immiticide® or Diroban™ is a good or safe fit. Both are melarsomine. Melarsomine has what is called a narrow spectrum of safety – more so than any other drug veterinarians administer to dogs. The difference between the treatment dose and a toxic dose is very small. Younger dogs, discovered before heartworms have caused serious damage generally tolerate Immiticide/Diroban (melarsomine) well – when given at the correct dose for their body weight and when clients strictly control the dog’s activities after the drug is administered. But once the damage heartworms cause becomes extensive, the chances of the drug being toxic are greatly increased. Those are what we call class 3 and class 4 stage dogs (the sickest) and, like any classification system, which class of heartworm disease a pet falls into is somewhat subjective and arbitrary. You can read about the stages of heartworm disease here. Beardow2004.pdf

High-risk treatment dogs generally do have warning signs. They are low in energy, tire and pant easily. They are often thin – although their potbelly may disguise that. They often have a cough – particularly when they are lying down relaxed. Dogs over 4-5 years that are high risk often show premature signs of aging - grey hairs on their face paws and muzzle. Their pulse may be visible on their neck. Heart murmurs are common. If those dogs are examined by x-ray or ultrasound, there are telltale signs of heart failure. They are often anemic and tests that measure the efficiency with which they move blood through their bodies are reduced. (CRT) Dogs that have heartworms discovered later in life often have elevated liver and kidney tests (serum AST, ALT, alkaline phosphatase, bilirubin, and urea nitrogen) Those dogs are also high-risk candidates for the use of melarsomine. Both manufacturers of melarsomine suggest a 3-dose, spread out administration protocol and strict post-treatment exercise restriction for high-risk dogs (4-6 wks of low-stress cage confinement). But the high risk remains (blood clots = thromboembolisms). Also, Some dogs and some owners just do not tolerate the long term caging of their pet. Those are issues that your veterinarian has little control over.

There is another major issue with melarsomine treatment. It’s expensive. Particularly when pre and post-treatment monitoring follows the recommendations of the American Heartworm to the letter. (ref) AmHtwmSoc2014.pdf That can put melarsomine treatment beyond the capacity of many US pet owners, most humane societies and most of the developing world to pay for it. (ref) Colby2011.pdf

Even when these guidelines are followed some dogs are not entirely cleared of heartworms by the two-dose or three-dose melarsomine treatment. That may be because the younger stages of heartworms, those not killed by melarsomine, went on to mature in the pet. But even some mature worms appear to resist the killing-effects of the drug. Traditionally, vets told clients that, perhaps 2-5% of dogs might still have a few heartworms after melarsomine treatment (its probably closer to 10% [ref] Isaza2014.pdf) But in a Louisiana vet school study that reviewed the real world files of 50 dogs that had Class II heartworm severity (=some symptoms, ie lingering cough or fatigue after exercise.) or greater, 14% died during or shortly after treatment. All of the surviving dogs received monthly preventative after their melarsomine treatment and of the 18 dogs that were tested (In office Snap test) 6 month later, 33% were still positive for living female heartworms – although most did go negative later. But we do not know from this study if those dogs (or the others) were truly free of heartworms - since male worm, immature female worms or female worms sterilized by the doxycycline or the monthly heartworm preventatives that were given would test negative as well. (ref) Maxwell2014.pdf
Besides, Snap tests are not nearly as sensitive low numbers of worms as some folks suppose. (ref) Klotins2000.pdf

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Doxycycline Wolbachia And Heartworms

Veterinary school parasitologists have neither the funds, nor the personnel to conduct ground-breaking research. But they do know that another filaria parasite of humans and, perhaps gorillas and monkeys (ref) Grove1982 Onchocerca volvulus, is very similar to the dog heartworm. The difference is that the adult human parasite resides in “boils” under the skin and is transmitted by biting flies, not mosquitoes. It causes a great deal of human suffering (ref) https://en.wikipedia.org/wiki/Onchocerciasis ; so Medical schools and international agencies spend a great deal of time looking for ways to control it. When I visited an area of the Amazon where River Blindness was a problem. I mixed ivermectin with Coca Cola and drank it weekly. (ref link to htm.) (photo and text, me w kids, doxy because ….. did not agree with me.)

Its been known since 1977 that a peculiar bacteria, Wolbachia lives within all stages of the dog heartworm’s cousin, Onchocerca (ref) Kozek1977.pdf Actually, that author saw them in dog heartworms in 1970 but thought they were just parts of the heartworm – not independently living things. In 1997, it was noticed that a cow, infected with another relative of the heartworm, recovered when it was given tetracycline. (ref) and on that basis, doxycycline was proposed to sterilize Onchocerca and prevent river blindness. In 2008, it was suggested that killing these bacteria, would eventually kill the Onchocerca worms themselves. (ref1, ref2) Hoerauf 2008.pdf Specht2009.pdf As time went by, it also became apparent that Wolbachia within these parasites was responsible for much of the inflammation that occurred in Onchocerca- infected humans and, most likely, in heartworm-infected dogs and cats as well. (ref1, ref2, ref3) SaintAndre2002.pdf Landmann2012.pdf Passeri2014.pdf

The inflammation Wolbachia is involved in is not confined to the heart and lungs– through complex processes even the pet’s kidneys might be effected. (ref) Monchon2012.pdf

There is some evidence that pulsing the dose of doxycycline, rather than giving it continuously, kills Wolbachia more efficiently. (ref) Makepeace2006.pdf There are also studies in progress in Georgia to see if minocycline is an alternative drug.

As far as the ability of minocycline versus doxycycline in reducing Wolbachia, there has not been any studies done directly looking at this. I do have a clinical trial ongoing right now that will attempt to answer this question but we have not finished this study yet.

Things rarely stay the same forever and Wolbachia might conceivably become resistant to doxycycline and minocycline as well – but for now, it can be very helpful for dogs and cats that have become infected with heartworms.

Slow Kill

For extended periods of time, Merial, the only maker of Immiticide (melarsomine) at the time, did not make their product available. (ref) The company never gave an explaintion for those outages; but the situation spurred interest throughout the dog heartworm research community in finding alternative treatment options.

Perhaps with that in mind, in 2008, a team of veterinary researchers based at the Veterinary schools of Athens Georgia and the University of Pennsylvania and others working in Milan and Parma Italy published results of the first detailed studies I know of that looked for an effective alternative to melarsomine therapy for heartworm disease in dogs.

When examined 9 months after beginning treatment with ivermectin and doxycycline, the group of dogs in that study that received doxycycline (the same drug group as tetracycline) had a 78.3% reduction in their mature heartworm burden. Those receiving melarsomine plus doxycycline plus ivermectin had a 92.8% reduction and those receiving only melarsomine no longer had any heartworms. Those figures lead me to conclude that 5 dogs in each group in the study just was not enough to draw broad conclusions as to which treatment option might be most effective, but sustained treatment with doxycycline and ivermectin was definitely quite beneficial. You can read the results of that study here. McCall2008.pdf

Very quickly thereafter, a number of articles appeared that were highly critical of what came to be know as the doxycycline/ivermectin “slow kill” method. The heartworm society (ref) was dead set against it. Some members suggested, without hard evidence, that this slow kill method produced false-negative snap tests after the treatment ended and that the dogs were probably still infected. They proposed, again without evidence that people using this method to treat their pets would be sloppy in giving their pets the monthly preventative they require after the treatment. They proposed that using the slow kill method would produce a super-strain of drug resistant heartworms. (ref) Drake2015.pdf Very little in the way of evidence was presented to back any of those claims up. Others articles echo those or similar opinions. (ref) Mandese2014.pdf Bowman2011.pdf Beardow2004.pdf Zoetis, a current manufacturer of melarsomine uses those criticisms in its marketing strategy. (ref) ZoetisDiroban2017.pdf

Others cited a more documented ramification for veterinarians suggesting the slow kill treatment: Melarsomine is FDA approved for adult heartworm treatment; doxycycline and ivermectin are not. If a dog does not do well subsequent to properly-administered melarsomine, the FDA stands behind that veterinarian. With a non-FDA therapy, they do not (Like the Walendas, there is no net).

In 2014, another Italian study documented the effectiveness of ivermectin and doxycycline given as an alternative to melarsomine. (ref) Mavropoulou2014.pdf Although considerable lung pathology resulted from the dying worms, one of the authors reported that the extent of lung pathology following melarsomine treatment was even greater. (ref)

The veterinary school in Auburn, Alabama has, on staff, one of the premier research scientists studying heartworm drug resistance. In 2011 he and his colleagues reported that of the four monthly heartworm preventative medications studies, moxidectin/imidacloprid (Advantage Multi®) topical drops were the most effective in preventing heartworms. (ref1, ref2 ) Blagburn2011.pdf Blagburn2016.pdf In a discussion a few years later, he told me that he believed that was because moxidectin persisted in the dog’s body longer than ivermectin did (because it is more lipophilic than ivermectin, it is more soluble in the fatty tissues of your pet’s body). By mid-month, little of the ivermectin at the first of the month remains in your dog’s system. Others confirmed that. (ref) Bowman2016.pdf Both studies were paid for by Bayer, the manufacturers of Advantage Multi ®; but other non-supported studies using moxidectin in cattle support their conclusions.

That knowledge, that moxidectin might be more efficient in killing heartworms, led veterinarians at Colorado State University College of Veterinary Medicine, North Carolina State University, University of Milano Veterinary Sciences and Università di Parma to begin trials to see if using Advantage Multi and doxycycline, rather than ivermectin and doxycycline might be more effective in treating heartworm-infected dogs. It is July of 2017,
Those studies are in progress, the vets are optimistic but the results are not in yet – or if they are -, I am not privy to them. They call it the MOXY protocol. Ames2017.pdf.
You can read it here. It is tentative Some preliminary Georgia data was presented at the August 2016 AAVP meeting. You can read that here. Savadelis2016.pdf

Emails from the European Groups:

April 3, 2017 : ................................................................................................................................... In my experience, the combination moxidectin/doxycycline showed a good efficacy and was able to decrease the risk of thromboembolic reactions. However, my data were obtained in field studies. Recently, in an experimental study (not from my group; it will be published soon) dogs were treated with moxi/inidacloprid per labeled dosage for 10 months and with 10 mg of doxycycline BID orally for 30 days. Throughout the study, dogs were not exercise-restricted. The efficacy in eliminating adult heartworms was 95.9%. One dog of 8 treated showed adverse events suspected to be a consequence of thromboembolism self-resolved. In my opinion, moxi/doxy is a valid alternative to classics melarsomine therapy.

April 4, 2017 :

We are also evaluating the efficacy of doxycycline combined with topical moxidectin (Advantage multi) and results are very promising. We currently recommend 10mg/kg/bid of doxycycline for one month and Advantage multi once a month for nine months. We observe: 1. Very fast elimination of microfilaria (30-60 days from the beginning of treatment); 2. negative antigen tests within several months from the beginning of treatment. The moxy/doxy combination appears to clear infection faster [than ivermectin], with antigen tests going negative at about 6 months. The ivermectin/doxy combo takes about 12 months to work. We have observed some coughing at around 2-3 months into the regime, but this is managed well with pred [prednisone].


Accoding to the Head of the NIH Clinical Parasitology Section, both the DNDi https://en.wikipedia.org/wiki/Drugs_for_Neglected_Diseases_Initiative and the WHO https://en.wikipedia.org/wiki/World_Health_Organization are hoping to make moxidectin available soon to treat the heartworm’s human cousin Onchocerca https://en.wikipedia.org/wiki/Onchocerca – for the same reasons it appears superior to ivermectin in dogs.

Airline image jpg

Just a word of advice. It would, in my opinion be exceedingly foolish for you to begin or attempt any of these treatments without the close supervision of your local veterinarian – much like attempting to do your own maintenance on the 737 airliner you plan to be on, on your next flight. I also cannot speak to the safety of using moxidectin in herding dogs with the MDR1/ ABCB1 mutation Odunayo2012.pdf But there is some evidence it might be a bit safer than ivermectin. (ref) https://www.ncbi.nlm.nih.gov/pubmed/22834856

Should I Feel Responsible For Causing Heartworms To Mutate And Become Resistant To Monthly Preventatives When I Agree To Use The Slow Kill Treatment Method For My Dog ?

I personally would not.

But there are no “shoulds” when it comes to guilt. It, like happiness, comes from within you with little regard for the facts.

I think in terms of the best interests of your dog and you, not some nebulous, unproven theory of the future. One that is really not confirmed by real-world data. Might an asteroid strike the earth during our lifetime and end all life forms? Perhaps. Might something I do for the benefit of a dog today have negative consequences for dogs in the future ? Perhaps. But by that time, pharmaceutical companies will probably have other medications than microcytic lactones to prevent and treat heartworms because they are so similar to related human parasites like onchocerca. Many are looking for those options now. (ref1, ref2) GatesFoundation2017pdf NIAID2017.pdf

A great deal of effort is being spent looking for different classes of drugs that might control canine heartworms if what we presently use becomes ineffective. (ref1, ref2, ref3) Mani2016.pdf Mani2016b.pdf Mani2016c.pdf

Besides, if you take steps to keep your dog heartworm larva (microfilaria) free with monthly preventatives during and after slow kill treatment, what you do has no effect on how things develop in the rest of the dog population. (ref) Atkins2017b.pdf In 2017 There are many brands of monthly preventative that will kill heartworms before they take up residence in your dog’s heart; but only Advantage Multi® (because it contains moxidectin) is FDA approved for the elimination of the microfilaria that allow the parasite – mutated or not – to transfer to another dog. (ref) AdvantageMultiProductLabel.pdf If you are opposed to that, other options are a primarily indoor life for your pet during its treatment, combined with a product like Vectra 3D® Vectra2017.pdf or K9 Advantix® II AdvantixII2017.pdf. If you use both Advantix and Advantage Multi the pet will receive double its suggested dose of imidacloprid. But imidacloprid is a low toxicity medication and I don’t think that would be a problem. Just be sure to place the drops in locations where the pet cannot lick it off.
There is another factor working here against the development of heartworm resistance. The larger the number of heartworm infected dogs and other canids not receiving monthly preventatives, the less likely a parasite species is to mutate. It’s estimated that only half of out-of-door, minimally maintained dogs have heartworms. (pftref) Colby2011.pdf That is about 19.5 million untreated dogs in the USA. It takes drug pressure on a species to encourage it to develop drug resistance. That large untreated pool of dogs makes it considerably less necessary for heartworm to make that mutation to survive. It has also been estimated that 91% of adult Florida coyotes carry and spread dog heartworm disease as well. (ref) Sacks1998.pdf That means there is even less pressure on heartworms to become resistant to monthly heartworm preventatives or the “Slow Kill” method of treatment.

There might be another advantage when one uses Advantage Multi as part of the “Slow Kill” process. The moxidectin in Advantage Multi helps kill the heartworms. But the imidacloprid that is also in the product kills fleas. Fleas are carriers of the same Wolbachia (W. pipientis) that we are trying to kill within the heartworms with doxycycline. (ref) Zurita2016.pdf No one knows if Wolbachia can move between hosts but other bacteria with an intracellular lifestyle can. (ref) Pizarro-Cerda2006.pdf Until we know more, providing a fresh source of Wolbachia bacteria from fleas is not something I would encourage.

Are There Alternative Ways To Remove Heartworms From Dogs ?

Advanced imaging techniques and specialized surgical skills are making it possible for veterinarians (generally at large institutions) to extract heartworms from the heart and pulmonary arteries. The technique requires superb judgment and hand-eye coordination. In most veterinary centers, folks with that talent dwell in the school’s interventional radiology department. (ref) Alho2016.pdf A vet school professor emeritus at, North Carolina State University told me they do quite a few of those surgeries there. He mentioned other institutions with good veterinary interventional programs were usually located in areas of high heartworm prevalence that bring them a lot of candidate dogs. Particular among them were the veterinary schools at the University of Georgia, University of Florida, Texas A&M University, Auburn and Colorado State. At those institutions there may be no more than one highly experienced individual. And since those folks may come and move on, the institution’s experience and success rate can fluctuate. (ref) Carey2011.pdf

It is quite rare to successfully remove all of the heartworms with these techniques. But critically ill dogs can often be stabilized and sufficient time gained for medical treatments to kill the worms that remained.

I rarely mention products by name. In this article, I mention Bayer’s Advantage Multi frequently. That is because presently there is no topical competing moxidectin containing product for dogs. I believe that the patent on moxidectin expired in 2011, so I am not sure why that is. Zoetis markets Proheart6, a twice-a-year moxidectin injection to prevent heartworms as well as some moxidectin-containing farm animal formulation. I personally avoid administering ProHeart® 6. (ref) ProHeart62017.pdf