Treating EPM in horses: Options and my choice for River

When my vet diagnosed River with equine protozoal myeloencephalitis, I had to learn a lot about treating EPM in horses in a very short time. (Read my post on detecting subtle signs of EPM.) Dr. Marquez recommended two FDA-approved treatments. After some frantic research, I chose an alternative option. I will describe these and other options below.

Above: A screenshot of the results of River’s initial EPM panel, obtained from UC Davis.

Warning: I am most definitely not a veterinarian nor a molecular biologist. Here I simply narrate my own experience learning about EPM treatments. Please feel free to correct any errors of interpretation and/or direct me to pertinent information I have missed.

See my earlier post on Detecting subtle signs of EPM in horses.

Jump to:

Treatment comparison chart
My vet’s first suggestion: Marquis (ponazuril)
The second FDA-approved option: Protazil (diclazuril)
An older FDA-approved option: Sulfadiazine/Pyrimethamine
After several hours of research, I decided on decoquinate and levamisole
Supportive care to reduce inflammation and increase comfort
Maintaining a healthy immune system
None of these drugs should be given except as treatment
A few questions
References

To read a peer-reviewed overview of EPM in horses, including FDA-approved treatments, click here: Reed et al., 2016.

To read about sarcocystis neurona, the primary cause of EPM in horses, click here: University of Saskatchewan summary, 2021. For a peer reviewed paper, see Dubey et al., 2015.

Treatment comparison chart

Above: Treatment comparison chart that summarizes the information covered below.

My vet’s first suggestion: Marquis (ponazuril)

Ponazuril is a metabolite of toltrazuril, an anti-protozoal used to treat coccidiosis. Both are static: they work by interfering with the reproduction of the protozoa but do not kill it. Ponazuril has the advantage of crossing the blood-brain barrier (brain here means all of the central nervous system). Both s. neurona and neospora hughesi (which also causes EPM though seems to be less frequent than s. neurona) attack the central nervous system, so anything meant to combat them will do so more effectively if it too can cross the blood-brain barrier.

Marquis is expensive

Marquis is the most expensive option for treating EPM in horses. It is sold in 15% w/w paste, which means that there is 150 grams of ponazuril in each gram of paste. A tube of Marquis contains 127g (19,050mg) ponazuril. At Valley Vet, one tube costs $373.39, or you can buy four for $1327.79, which saves you $165.77.

You’re going to need at least four.

Maker Boehringer Ingelheim recommends a single loading dose of 15mg/kg (6.8mg/lb), followed by 27 days of 5mg/kg (2.27mg/lb). For a 1,000lb horse, that’s 68,090mg of Marquis, or 3.57 tubes. For a 1,200lb horse it ends up being 4.29 tubes. Valley Vet claims a tube lasts seven days for a 1,200lb horse, which is true if you don’t count the loading dose day.

Even River, who probably weighs about 850lbs, would need a bit more than three tubes. No matter how you look at it, Marquis is expensive.

What about generic options?

They do exist.

Heartland Vet Supply sells a tube that contains 18,000mg of ponazuril for $101.96. (You’d need 4-5 depending on how big your horse is.)

Rood & Riddle sells a powder in various formulations (and an oil suspension). $236.50 gets you 30 scoops of 3g ponazuril, which is more than 30 days of maintenance dose for a 1,300lb horse.

If I were to administer ponazuril, I’d go with the Rood and Riddle option.

It might be worth it if ponazuril worked.

Furr et al. (2001) reported an efficacy of 62%. There is some evidence that it works better as a preventative (Furr et al., 2006).

Its lack of efficacy might be due to inter-horse variability in the absorption of ponazuril (measured in CSF; Furr & Kennedy, 2020). Hint: administer with corn oil to increase concentrations. (erm…)

I found few published papers and must conclude not a lot of research is being done. I might have missed things, but a quick perusal of recent dissertations (e.g., Helber, 2024) suggests that I haven’t.

Fun fact!

A derivative of ponazuril, ACD856, is being studied for use in treating neurodegenerative disorders–Alzheimer’s Disease is the most common– in humans. Read about it here: Dahlström et al., 2021; Önnestam et al., 2023. Anti-parasitic drugs are just so cool!!

The second FDA-approved option: Protazil (diclazuril)

When I balked at buying Marquis, my vet suggested Merck’s Protazil, the FDA-approved brand for diclazuril. Protazil is 1.56% diclazuril in pellets; Merck recommends 1mg per kg for 28 days. Their 2.4lb bucket provides the full treatment for a 1,274lb horse. The least expensive options I could find was $880.99 at Rood & Riddle and $898.99 at Valley Vet.

Diclazuril is also a triazine anti-protozoal drug used in all sorts of animals. As with ponazuril, oral bioavailability of diclazuril seems to very greatly from horse to horse (CITE). Its efficacy is similar, probably due to it being static (like ponazuril) rather than cidal (which would mean it kills the protozoa).

Caveat: Bacteriocidal (cidal) antibiotics have been assumed to be superior to bacteriostatic (static) antibiotics, but the evidence suggests there is no difference in efficacy (Wald-Dickler et al, 2017). Protozoa are not bacteria, but the logic for the preference for cidal treatment is the same.

Off-brand options?

Rood and Riddle offers diclazuril in paste, suspension, and powder. Going by Merck’s dosing recommendations (I cannot find the peer-reviewed article I had to cite a few months ago…) of 1 mg diclazuril per kg (0.45 mg diclazuril/lb), you’d need 450mg/day for a 1,000lb horse. A 500mg powder packet costs $6.93. (That’s $207.90 for 30 days.) Or you can pay $187.80 for a 30-scoop jar, with each scoop containing 500mg.

You would be overdosing unless you have a giant horse, especially because even the recommended dose is far more than enough (Pusterla et al, 2021).

There are many other off-brand options for diclazuril. Many are combined with levamisole and/or vitamin E.

Fun fact!

Diclazuril is also FDA-approved for use to kill parasites in broiler chickers. It has been shown to protect against congenital toxoplasmosis in mice (Oz & Tobin, 2014).

An older FDA-approved option: Re-balance (Sulfadiazine/Pyrimethamine)

Re-balance is a combination of the sulfa-based antibiotic sulfadiazine and pyrimethamine, an anti-parasitic and anti-malarial drug. Both have been used in humans to treat a range of infections. The combination is used to treat toxoplasmosis. Both drugs have been used so extensively in humans and animals that there is considerable resistance.

Sulfadiazine/pyrimethamine is a first generation method for treating EPM in horses and must be used for much longer than ponazuril and diclazuril, at least 90 and as much as 270 days. Dosage is 4ml /110lbs per day. Each mililiter contains 250 mg sulfadiazine and 12.5 mg of pyrimethamine. That is 36.36ml for a 1,000lb horse, or 9,090mg of sulfadiazine and 454.4 mg of pyrimethamine (a 20:1 ratio).

Re-Balance is sold in one quart (946.4ml) bottles. It is cheapest at Rood & Riddle ($290). One bottle will last 26 days for a 1,000 horse. That adds up to $1004 for 90 days and $3,012 for 270 days.

Fortunately my vet didn’t even suggest that one!

Off-brand options?

Rood & Riddle sells 30- and 45-scoop jars of powder. each scoop has 10 grams of sulfadiazine and 100 mg of pyrimethamine, so just slightly more than what you would need for a 1,000 horse. You only save one cent by buying the 45 scoop jar, which costs $137.19. At that price, 90 days would cost $274.38, and 270 would cost $823.14. Far less expensive than Re-balance, but still not likely to get rid of EPM.

There are other options, but it didn’t take me long to decide this was not going to be a smart option to take.

(not-so) Fun fact!

Sulfadiazine/pyrimethamine is used to treat toxoplasmosis in humans, particularly for AIDS patients who suffer toxoplasmic encephalitis (e.g., Podzamczer et al., 2000 but there are many older papers). Unfortunately, longterm use (which was what was done) can result in kidney failure (e.g., Diaz et al., 1996).

Given the longterm nature of treating horses with sulfadiazine/pyrimethamine, the possibility of kidney damage is a concern. According to Dr. Ellison, the compound may be toxic after 30 days.

After several hours of research, I decided on decoquinate and levamisole

As soon as I got off the phone with my vet, I immediately searched peer-reviewed research and realized that ponazuril and diclazuril were very similar. Neither had a very good track record, but diclazuril was cheaper, so I placed an order for Protazil with Valley Vet. Then I kept reading.

Several people on Facebook pointed me towards the EPM Horse Support Facebook page. The most telling recommendation came from Dr. Bob Rogers, an endurance veterinarian whom I had come to respect based on his comments on many posts.

The EPM Horse Support group attracts horsepersons of all disciplines dealing with EPM. Many use different treatments, but the page purports to adhere to the findings of Dr. Siobhan Ellison. Dr. Ellison has a PhD in molecular biology and is also a vet (DVM). Her research focuses on the molecular biology of protozoal diseases. She started with identifying the different antigens that can identify an immune response to s. neurona (e.g., Ellison et al., 2001).

A note on the research

Much of the research on EPM diagnoses and treatment is based on in vitro studies and on rodent models. There are also a lot of articles that assess serum levels of the drug being tested. This is how we know that horses have very individualized responses to ponazuril and diclazuril treatments. (If I were writing a research paper I would have cited the last two sentences. Maybe I will add it later!)

It is expensive and time consuming to conduct research with horses. To the best of my knowledge, there is only one clinical study that provides support for the efficacy of decoquinate and levamisole as EPM treatment (Ellison & Lindsay, 2012). However, this paper builds on an extensive body of research and in turn contributes to furthering our understanding of EPM. Dr. Siobhan Ellison’s website Pathogenes contains links to most of the relevant papers as well as explanations helpful for those of us who are not trained in molecular biology and/or veterinary science.

On reading papers

Reading the paper can be confusing if you do not have experience reading academic papers. It can even be confusing if you are experienced and don’t know the jargon. (For example, I had to look up the acronym ELISA. It means enzyme-linked immunosorbent assay, which I had sort of figured out–within my limited understanding of the topic–but needed to confirm.) The easiest way to read a scientific paper is to do so in this order: Abstract, method, results, top of discussion (where good authors put the results in plain English), final paragraphs, and then, if you are still interested, the introduction.

A summary of Ellison & Lindsay, 2012

In the simplest terms! There is a lot going on that I have little hope of understanding fully (e.g., the differences among s. neurona phenotypes, specifics of testing, vaccination…). I am only going to address what I deem relevant (and that I can understand without getting another degree).

Broadly, the study had two aims: (1) test the presence of s. neurona antibodies in horses with and without clinical signs of EPM and (2) test the efficacy of treating EPM with a combination of decoquinate and levamisole. (More on both these fascinating drugs below.)

The researchers used 141 horses that had been diagnosed with EPM based on symptoms along with a control group of 100 normal (non-EPM-symptomatic) horses. They tested the sera (plural of serum, meaning serum samples) of 100 horses in each group.

Presence of s. neurona antibodies

As you can see in the table below, the majority of the “normal” horses were positive for one of the three s.neurona phenotypes, but significantly (p < .001) more of the suspect EPM horses were (84%).

Above: Detailed report of sera analyses (Table 1; Ellison & Lindsay, 2012). As expected, significantly more horses with clinical signs of EPM tested positive for one or more of the s. neurona phenotypes. What is interesting to me is that EPM horses were significantly more likely to have mixed infections of SAG1, whereas apparently normal horses were more likely to test positive for SAG6. (The difference for SAG5 is not statistically significant.) Someone more educated than I might be able to say something meaningful about this.

If you read the discussion, you’ll see that SAG6 is indistinguisable from s. falcatula, in antibody tests. S. falcatula is a parasite that attacks birds via opossums. Not horses.. but see Borges-Silva et al., 2020 if you want to dive into a rabbit hole. Fascinating stuff. Maybe in another life I’ll be a molecular biologist.

Treating with decoquinate and levamisole

The clinical trial portion of the study was carried out with 141 EPM-symptomatic horses that were also seropositive for s. neurona. The horses were administered decoquinate (0.5mg/kg) and levamisole (1mg/kg) for ten days, then retested for titers at 4-6 weeks.

Why decoquinate?

Ellison and Lindsay’s (2012) rationale for testing decoquinate was Lindsay’s (2001) patent that reported the effectiveness of its use to kill states of s. neurona in vitro. The same or similar research is reported in a later peer reviewed article (Lindsay et al., 2013). (Research articles might be difficult to read, but they are far easier–at least for me–than patents!)

Decoquinate is inexpensive and effective for killing s. neurona in a short time (both excellent arguments for its use even if its effectiveness is similar to that of the FDA-approved treatments).

Why levamisole?

Read a summary of the history of levamisole on the Pathogenes website: Levamisole nonenzymatic breakdown products.

Levamisole is a fascinating drug. It was originally developed as an anti-parasitic to kill worms in fish and livestock. Among other things, many of which are poorly understood, levamisole may enhance immune response. It appears to be a nicotinic acetylcholine receptor agonist, which means it acts like acetylcholine, a neurotransmitter essential for cognitive processes (including attention, learning, and memory), muscle function, and digestion. In simple language, acetylcholine makes it possible for our brains (and bodies) to work.

As a nicotinic acetylcholine receptor agonist, levamisole can stimulate neural communication, facilitating the transmission of messages throughout the brain and body. That is how it kills parasites–it causes continual neuron firing that results in spastic paralysis of the organism.

Ellison and Lindsay (2012) argue that one possible explanation for the failure of FDA-approved EPM treatments is that they fail to address inflammation and nerve damage. Levamisole can do both and more.

Results

The results of the clinical trial were very encouraging. Almost all the horses (93.6%; see table below) had fewer clinical signs. A full 89.3% had decreased titers. Given that levamisole alone could explain some decrease in symptoms, and titers reflect immune response and can take a long time to subside, this datum is more impressive.

Above: Table 2 from Ellison and Lindsay (2012). The numbers are much better than in studies reporting the efficacy of FDA-approved treatments.

Case study: It worked for River!

I treated my mare River with decoquinate and levamisole for ten days, using Rood and Riddle’s compound. I bought the 30-scoop jar; each scoop contains 250mg decoquinate and 500mg levamisole. It cost $80 (I only know that by looking at my credit card statement). The protocol used in Ellison and Lindsay (2012) was 0.5mg/kg decoquinate and 1.0mg/kg levamisole. River weighs around 850 pounds, or 385.55kg. This would be 194.28mg decoquinate and 386.55mg levamisole.

Yes, the scoop contained more decoquinate and levamisole that necessary. I figured some would be lost in the eating, and it wouldn’t kill River to be slightly overdosed. The ratio would be correct.

My vet told me to give River a full dose of banamine (8cc) for 3 days and a half dose for two days. I figured it wouldn’t hurt.

By the end of the ten days, River’s stringhalt had disappeared.

Levamisole follow-up

After the 10 days (plus several days of no treatment so we could do a few slow LDs at the Feliz Cumpleanos ride), I gave her 428mg levamisole for 30 days, per my vet’s instruction. I could see the logic, though at the end of the 10 days, she was symptom-free. I used Levamed, a pig wormer which contains 1.111g of levamisole per 1g. (River needed 385.55mg; to calculate, use dimensional analysis: 1.111g Lev/1g Levamed = ?g Levamed/ 0.38555g lev; 1.111*0.38555 = 0.428g or 428 mg.)

I weighed the Levamed with this scale and sprinkled it over a tiny amount of Unbeetable Complete, which I dampened just enough to make the powder stick. To be sure River ate all of it, I fed it midafternoon when she had nothing else to eat.

Above: Scrambling over rocks in the high sierra. Not long after River’s second titer test after treatment with decoquinate and levamisole we went on a technically challenging 27.5 mile ride. If she had had any neurological issues, we’d probably be at the bottom of a cliff somewhere.

Extra benefits of levamisole seen in River

River never had pronounced EPM symptoms. The few she had–the most obvious being stringhalt in her right hind–disappeared before the 10-day D/L regimen ended. Interestingly, she also had very good gut sounds starting around the fourth day of the D/L treatment, and continuing past the 30 days of levamisole.

She also became much more flexible. I have been doing carrot stretches with River since I got her, using a carrot to make her reach as far back as possible. My other horses have all been able to reach their stifles easily. Some reach their hips. River has always had a tough time getting anywhere near her stifle; some days she was reluctant to stretch at all. (Compare this video of River struggling to stretch to the flexible horses in the one linked above!) After about 15 days of levamisole, River suddenly started reaching without hesitation clear to her stifle.

I am not sure the 30-days of levamisole were necessary, but I did not think they would hurt. They may have had extra benefits.

Serological evidence of the efficacy of treating EPM with decoquinate and levamisole

From the beginning, my vet was set on re-testing titers 4-6 weeks after ending the D/L treatment. I agreed, but I was hoping to put it off a few weeks. I thought it unlikely that titers would drop that quickly. Dr. Marquez was keeping track though, and she called me to remind me to draw blood at six weeks. I drew blood and took it in 6 weeks and one day after River finished the protocol. A week later we had the results. Her titer had dropped from 1280 to 160.

Above: Results of River’s second EPM panel. The titer dropped 87.5%. My vet was very impressed and deems this conclusive evidence for using decoquinate and levamisole. I tend to agree.

Why UCD’s SarcoFluor?

I’ll address this question before someone asks why I did not use Pathogenes. When my vet initially wanted to test for EPM, I had never heard of Pathogenes, and UCD has an excellent equine vet school.(It’s an excellent research institution all around!). For the retest, it was best to use the same facility.

Pathogenes offers more complete analyses that can give more insight into possible causes of neurological symptoms. I would not hesitate to use them if more information were necessary. I would also strongly recommend signing up for one of their trials.

Where to get decoquinate and levamisole

Once I had convinced my vet to try decoquinate and levamisole, I looked for options. As mentioned above, I went with Rood & Riddle‘s compound. This was largely due to their reputation and the convenience of the compounded formula. There are many other options!

Chewy offers a compounded powder that looks identical to the one I purchased from Rood and Riddle.

There are many other compounds out there, but I cannot recommend any. Some do not even tell you the concentrations, some have incorrect ratios of decoquinate to levamisole, some would be impossible to measure, and some have other ingredients, such as megadoses of Vitamin E. All require prescription.

You can buy both drugs without a prescription, if you are willing to get the livestock wormer formula and do your own measurement, as I did with levamisole.

Deccox seems to be the best product for decoquinate. You can get a 52lb bag at Valley Vet, which seems excessive unless you are preparing for a parasite apocalypse. You can get a 10lb bag at Revival for $35. Both are 0.5% decquinate, or 2271 mg/lb. At the dose of 0.5mg/kg, a 1000lb horse would need 227mg a day, about 0.10 pounds or 45.36 grams.

Levamed works well for levamisole. You can get it at Valley Vet or Tractor Supply or even Amazon.

Fun facts!

Decoquinate and levamisole are fascinating drugs! Here are just a few tidbits:

Decoquinate

Decoquinate (Deccox) is fed to poultry raised for human consumption, so unless you are eating only organic chicken, (or no chicken at all), you’ve probably consumed a bird that’s been fed Deccox as a prophylactic. It has the potential to kill all sorts of parasites, and has been investigated extensively for use in animals. There is potential to treat diseases such as malaria and toxoplasmosis but research in humans has been limited (Santos Souza et al., 2022).

Levamisole

Levamisole is used as a cocaine adulterant (Solomon & Hayes, 2017). It is metabolized into aminorex, a stimulant once marketed as a weightloss drug. In horses, levamisole metabolizes into aminorex and pemoline (Adam et al., 2024.) Pemoline is also a stimulant, used to treat ADHD until side effects proved untenable. Both are banned drugs for horse racing and endurance. Presumably horses testing positive for aminorex who were being treated for EPM gave the industry a headsup!

Levamisole has anti-depressant effects and some potential for use in treating Alzheimer’s disease (Akkaya et al., 2024). There are many older studies of its potential use to treat multiple sclerosis (e.g., Massaro et al., 1990), but scientists (e.g., Cortes et al., 2022) have since discovered that levamisole itself can cause demyelination (deteriorization of the myelin sheaths that speed up neural transmission along axons that causes symptoms of MS).

Levamisole has been tested as a COVID-19 treatment, and in at least a few randomized controlled experiments improved outcomes significantly compared with a control group (e.g., Firozabad et al., 2021; Pourahmad et al., 2024), but also demonstrated the potential to worsen late stage COVID )(Al-Kuraishy et al., 2021).

In fact, levamisole has many undesirable side effects in humans, the worst being  agranulocytosis. This–plus the fact we do not fully understand what it does–suggests that giving it to horses all the time may be an error. Besides, it is doping.

Supportive care to reduce inflammation and increase comfort

As mentioned above, my vet recommended five days of banamine. It really couldn’t hurt. Some may recommend bute instead. Luckily, I prefer banamine primarily because I can give it intravenously and therefore know exactly what dose the horse gets and when I can expect it to take effect. Generally it’s best to do whatever your vet recommends.

Others mention giving dexamethasone to treat inflammation. I would not have given River dex unless my vet asked and gave convincing reasons, although I know she tolerates it well (we had to use it to stop her coughing after she ate a lot of dusty hay meant for cattle). Dexamethasone–a corticosteroid– can suppress the immune system (e.g., Kreutzfeldt et al., 2023). It can also increase the probability of laminitis (read this article on the dangers of dex).

The importance of Vitamin E supplementation

Most protocols for dealing with EPM recommend supplementing vitamin E. It is assumed that Vitamin E will help horses recover from nerve damage. When my mare Lady was diagnosed with sweeney shoulder, my vet had me give her megadoses of vitamin E.

There are many products that include (or target) vitamin E. The most important thing is that you take into consideration whether it is natural (d-alpha-tocopherol) or synthetic (dl-alpha-tocopherol). Natural is more bioavailable (e.g., Kane et al., 2010).

My vet recommended 7,000IU a day. I aim for 5,000IU d-alpha-tocopherol now. She gets ~1,000IU in her Purina Enrich (no idea if natural or synthetic), and a negligible amount in her alfalfa and bermuda grass hay. I give her about 5 pounds of alfalfa and 10 pounds of bermuda per day, but how much vitamin E it contains is anybody’s guess. (In late winter and spring she is on green grass and probably doesn’t need supplementation!)

Before the EPM diagnoses, I gave River two scoops of KER Elevate (each scoop has 1,000IU). I have discovered that she won’t eat more than three scoops, so now I give her three scoops of Elevate and two capsules of Puritan’s Pride Vitamin E (1,000IU each). I used to give them to my mare Lady after her sweeney shoulder diagnosis. Lady would just eat the capsules like candy. Sadly, I have to break them open and dribble the contents on River’s feed, but at least she will get the vitamin E that way.

Maintaining a healthy immune system

**I don’t have time to add citations to all of this. Please comment with references if you can!

Most horses naturally fight off the protozoa and never develop EPM. Part of this is exposure–try to keep possum poop out of horse water and feed! However, a lot of this depends the individual horse’s immune system. An increasingly large body of research highlights the importance of the gut biome for a functioning immune system in horses and humans (e.g., Chaucheyras-Durand et al., 2022 [horses]; Wiertsema et al., 2021[humans]). As such, the best thing you can do to prevent EPM is to provide your horse with a healthy diet and sufficient exercise.

Diet

Healthy equine diet is the province of nutritionists, but all horsepeople should know the basics. Horses should eat a diet primarily composed of forage (hay or pasture), but they should also receive all of the necessary nutrients to support bone and gut health. If your hay does not provide that, then targeted supplements or a good ration balancer can provide the deficits. (I feed Purina Enrich.) Although many good feeds also provide enough nutrients, you must make sure to feed enough of them to guarantee sufficient quantities. For horses that are in work and/or not easy keepers, I feed other Purina feeds (e.g., Purina Senior Active) with Outlast, a gastric support supplement with good supporting evidence of efficacy.

Supplements such as Outlast can help prevent ulcers, but they can still happen under stressful conditions. Competition and/or travel can cause stress that can be addressed with targeted ulcer treatments.

Exercise and social life

Horses are less stressed when they have room to move around and are near other horses. Horses are very social creatures. Try not to stress yours out by isolating them.

Fit horses are healthy horses. Even if your horse has EPM and is in treatment, it will benefit from appropriate exercise. Your vet will be able to give you targeted advice. Mine told me to keep conditioning River as usual.

Of course, it would not be a good idea to do anything very stressful, because stress compromises the immune system and can cause worsening EPM symptoms.

None of these drugs should be given except as treatment

Keeping your horse healthy and fit can help maintain its immune system so it can fight the protozoa. Using drugs that treat EPM symptoms is not a good way to prevent them from occurring.

Don’t use them as a preventative

I see a lot of people talking about using one or more of these drugs as a preventative. I’m not a vet nor a molecular biologist, and I am not going to bother with citations here…. but this is just a terrible idea. Overuse will cause resistance. You’ve probably heard of antibiotic resistance. This is the same thing… anti-parasitics won’t work any more if people give them all the time.

Read Dr. Ellison’s commentary on the topic (she is an expert): Treating asymptomatic horses for EPM is a bad idea

Don’t overdose

Any medication is hard on the kidneys and liver. I’ve come across studies that show that toltrazuril and pyrimethamine can cause renal failure. There are undoubtedly many more studies I haven’t seen.

As mentioned above, there are side effects that can be worsened with overdosing. This is especially important when it comes to levamisole. Depending on the dose, levamisole can enhance the immune system, suppress it, or put it in overdrive (as happened when given to patients with advanced stages of COVID–it made the cytokine storm worse). It can cause agranulocytosis.

Just think about what it does to parasites 😉

A few questions

From my layperson’s review of the relevant literature, I could make what I believe was an informed decision about my mare’s treatment. I believe there is more evidence supporting the decoquinate and levamisole protocol than any other treatment. My personal experience with a single case supports this belief. That said, there are a few questions I would love to have answered.

Is there any experimental evidence that decoquinate and levamisole decrease symptoms of EPM and associated titers?

The study reported in Ellison and Lindsay (2012) is not an experiment (there was no random assignment nor true control group). As a statistician, I would like to see a double-blind experiment in which horses are assigned to one of five groups: decoquinate only, levamisole only, decoquinate and levamisole, ponazuril (or diclazuril) and decoquinate, and a control group that is not medicated.

How much of the effects reported in Ellison and Lindsay (2012) and anecdotally are due to levamisole versus decoquinate?

The experiment I propose above could provide evidence to resolve this question. I am wondering if levamisole potentiates decoquinate and/or decreases the symptoms of EPM alone sufficiently to be considered a “cure.” We are assuming here that the titer decrease is entirely due to decoquinate… but is it?

To what extent does decoquinate cross the blood-brain barrier?

Someone on the EPM Horse support group brought up this question, and I have not been able to find satisfactory evidence that it does, beyond the fact that it appears to decrease EPM symptoms and lower titers (Ellison & Lindsay, 2012).

Any other questions?

If you have any other questions, please share them. I have had a lively exchange with Dr. Ellison, who has corrected many of my misconceptions. She may agree to an in-depth interview if I have more intelligent questions than I was able to come up with on my own!

References

Akkaya, H., et al. (2024). Drug repurposing for veterinary parasitology: Exploring novel applications. Drug Development Research, 85(4), 221–230. Wiley. https://doi.org/10.1002/ddr.22184

Adam, M., et al. (2024). Detection of levamisole and its metabolites in horses after oral levamisole administration over seven days. Unpublished manuscript. PDF available at https://jessicaeblack.org/wp-content/uploads/2025/08/Adam-et-al.-2024.pdf

Borges-Silva, W., de Jesus, R. F., Ferreira, R., & Gondim, L. F. P. (2020). Reactivity of horse sera to antigens derived from Sarcocystis falcatula-like and Sarcocystis neurona. Frontiers in Veterinary Science, 7, 573016. Frontiers Media SA. https://doi.org/10.3389/fvets.2020.573016

Chaucheyras-Durand, F., et al. (2022). Probiotics and their role in health and disease in horses. Animals, 12(3), 345. MDPI. https://doi.org/10.3390/ani12030345

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