Havemeyer EPM Meeting Coverage

Here are two presentation summaries from the 2022 Dorthy Russell Havemeyer Foundation’s EPM Advances in the Field Symposium.
veterinarian performs spinal tap to confirm or rule out EPM in a horse
In most cases, performing a serum:cerebrospinal fluid (taken by spinal tap) titer ratio to confirm or rule out EPM in horses—versus treating without testing in this manner—substantially decreased cost for the owner. Courtesy Dr. Sarah Colmer/PennVet

As long as opossums saunter through horse properties at night, leaving behind feces contaminated with Sarcocystis neurona or other protozoan oocysts or sporocysts, we’ll continue seeing cases of equine protozoal myeloencephalitis (EPM) in horses. Meanwhile, researchers of various ilks—equine clinicians, pathologists, parasitologists, epidemiologists, and others—continue to study the disease and how to best diagnose and treat it.  

To that end, 28 delegates representing academia, private practice, and industry congregated in Asheville, North Carolina, in October 2022 for the Dorothy Russell Havemeyer Foundation’s EPM Advances in the Field Symposium to learn about and discuss the latest EPM research. 

The Dorothy Russell Havemeyer Foundation was founded in 1979 to conduct scientific research to improve the general health and welfare of horses. It’s focused on a variety of topics, including infectious disease and, specifically, protozoal myeloma. Among other activities, including supporting principle investigators at several institutions, the foundation conducts special workshops like the EPM one.  

Many of the delegates presented on a variety of subjects; we’ve summarized two of those here.

Treating EPM in Horses: Comparing Serum:CSF Titer, Treatment Trial Costs

Short summary: Performing a serum:cerebrospinal fluid titer ratio to confirm/rule out EPM in horses (versus treating without that test) substantially decreased cost for the owner.

When veterinarians are considering an equine protozoal myeloencephalitis (EPM) diagnosis in horses, they typically have three routes they can take: Treat the horse based on measuring serum (a component of blood) titers against the causative protozoa; treat based on serum titers plus a spinal tap; or treat the horse based on clinical signs alone. All paths can be expensive, so University of Pennsylvania researchers recently examined the accuracy and costs of each for horse owners and determined, at least in their patient population, the option that might sound like the cheapest—beginning with a treatment trial without previous testing—likely isn’t. 

Sarah Colmer, VMD, Dipl. ACVIM, a neurology fellow at the PennVet School of Veterinary Medicine’s New Bolton Center, in Kennett Square, and her advisor, Amy Johnson, DVM, Dipl. ACVIM, recently conducted a retrospective study of 681 neurologic cases to assess the accuracy and costs of diagnosis and treatment using different approaches. Colmer presented their results at the Dorothy Russell Havemeyer Foundation’s EPM Advances in the Field Symposium, held in October 2022 in Asheville, North Carolina.  

Exposure to EPM Protozoa Is Common 

Many U.S. horses have been exposed to the protozoan parasites that cause EPM, Sarcocystis neurona and Neospora hughesi. Exposure means a horse has encountered these organisms; it is not synonymous with true clinical neurologic disease. 

Colmer cited a 2017 study in which researchers reported seroprevalence nationally. “Overall seroprevalence for Sarcocystis and Neospora was actually higher than a lot of previous studies, with 78% and 34% respectively, overall,” Colmer said, “and 31% of these healthy equids were seropositive for both organisms, and 18% were seropositive for neither.”  

PennVet’s equine patient population consists of mostly sport horse referrals from the mid-Atlantic region. “We do occasionally see EPM,” said Colmer, “but we see a couple other more common conditions: cervical vertebral stenotic myelopathy (Wobbler syndrome), as well as equine degenerative myeloencephalopathy (EDM), and EDM is our most common postmortem confirmed diagnosis in our neurologic horse population. 

“These conditions often present indistinguishably and, so, diagnostics, of course, are going to be really important in terms of decision-making and management moving forward,” she added. 

EPM Treatment Trial: Not Always So Cheap 

In the current study Colmer and Johnson included horses with signs of neurologic disease that underwent a complete neurologic exam, EPM antibody testing on serum and CSF, and, if euthanized, neurologic necropsy. Colmer reported postmortem exams were performed on 196 horses; 23 (12%) of those were diagnosed with EPM (postmortem diagnosis is the only way to definitively diagnose the disease). 

Overall, more than 80% of horses had positive serum titers and more than 50% had positive CSF titers, which depicts again just how common S. neurona and N. hughesi exposure is among horses. They estimated costs for serology alone, CSF centesis (spinal tap) and analyses, and treatment (using Marquis [15% w/w ponazuril]), based on PennVet’s pricing. Although they also use other FDA-approved medications to treat EPM, they chose ponazuril to represent cost for this data set. Colmer reported their results: 

  • Specifically, 83% of horses were S.-neurona-positive on serology. 
  • For any individual horse there was a 12% chance EPM would be the diagnosis. 
  • CSF centesis: 
  • Increased the cost by $547 (in diagnostics) in 12% of cases. 
  • Decreased the cost by $1,030-2,060 (the cost of one or two months of treatment) in 88% of cases. 
  • Overall accuracy was highest per serum:CSF (2 4/3) titer ratio. 

“The cost of performing a spinal tap is going to increase 12% of cases’ bill,” Colmer explained. “However, in 88% of cases you might actually decrease the ultimate cost to the client if you’re not going to pursue treatment based on the fact that most horses will be negative based on these diagnostics.”  

Different Regions Could Mean Different Treatment Costs 

Colmer acknowledged that veterinarians cannot necessarily extrapolate data from the PennVet referral caseload across all populations. “There are different EPM prevalences in different parts of the country, and so we are restricted to applying this information to and from the population around us and, for that reason, one of our future directions that we’ve discussed is potentially doing this on a larger scale and including more of a multicenter retrospective study to get numbers that might include other areas of the country. This would allow us to collect data from a wider population of horses that is more reflective of and applicable to the general population.”  

EPM Drugs, Disease Duration Don’t Impact Post-Mortem Testing Results 

Short summary: Pathologists detected S. neurona DNA in preserved tissue from horses with acute and chronic neurologic disease, with and without EPM treatment history.

Sarcocystis neurona, a protozoan parasite that causes EPM
Sarcocystis neurona, one of the protozoan parasites that causes equine protozoal myeloencephalitis (EPM), seen within an infected horse’s spinal tissue with associated inflammatory cells. Courtesy Dr. Rebecca Ruby

When a horse doesn’t survive the debilitating neurologic disease equine protozoal myeloencephalitis (EPM), the body might be sent to necropsy so pathologists can confirm the cause of disease, whether for the owner’s understanding, insurance purposes, or both. To confirm the diagnosis of EPM, pathologists must be able to see the causative protozoa, Sarcocystis neurona or Neospora hughesi, in tissue samples under the microscope or detect protozoal DNA with polymerase chain reaction (PCR) testing. But until recently it’s been unclear whether EPM treatment, disease duration, and tissue sample preservation methods interfere with results. 

Rebecca Ruby, BVSc, MS, assistant professor at the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL), in Lexington, recently sought to examine the effects of these variables, along with Jennifer Janes, DVM, PhD, Dipl. ACVP. Ruby presented their results at the Dorothy Russell Havemeyer Foundation’s EPM Advances in the Field Symposium, held in October 2022 in Asheville, North Carolina. 

Ruby looked at tissue samples and PCR test results for S. neurona, the primary causative agent of EPM (and the one they typically test for in Central Kentucky), from 199 horses with neurologic disease tested from 2010 to 2021—the lab has a high equine caseload and keeps an extensive library of samples for research. Of those horses, 78 had detectable DNA with cycle threshold (CT) values from 26.56 to 40.08 (average of 34.30). A CT value indicates the point where a real-time PCR diagnostic result changes from negative to positive (think about the time it takes for the test line to appear, or not appear, on a COVID-19 PCR test, for instance). 

Within this group 60 (75%) horses had experienced neurologic signs for a duration of one day to three years, with a mean of 60 days and a median of 10 days. Ruby reported that 31 (39%) of the horses were known to have received antiprotozoal treatment prior to death.  

Pathologists tested 56 formalin-fixed paraffin embedded (FFPE) samples and 19 fresh nervous tissue samples, with average CT values of 34.78 and 32.83, respectively. 

She described additional findings: 

  • In two cases pathologists detected S. neurona DNA in horses with noncompatible histopathologic lesions—in other words, they didn’t see spinal cord damage that would suggest the horses had EPM, but the animals tested positive for it regardless. 
  • In 121 horses they didn’t find S. neurona DNA. Pathologists observed nervous system inflammation in 40 (33%) cases, warranting a presumptive diagnosis of EPM. “It’s like our constellation of inflammatory changes considered consistent with EPM, so we’re not seeing the protozoa necessarily, we are not identifying the DNA,” she explained. “We’re just saying, ‘We don’t know things that do this in horses that are not EPM.’” 
  • In the remaining 66% of cases, they pinpointed something other than EPM or a noninflammatory neurologic condition (i.e., cervical vertebral stenotic myelopathy, aka Wobbler syndrome) as the primary diagnosis. 

“Out of this whole group, it’s really important to recognize 66% of those horses had a diagnosis that was not EPM,” said Ruby. “So, these are horses that might have been on the necropsy floor due to a history of acute onset neurologic disease, resulting in testing for S. neurona immediately, and then they were diagnosed with something else.” 

Ruby said this subset of suspected, but not confirmed, cases of EPM is the group of horses she and her colleagues hope to study further, looking for other protozoal organisms besides S. neurona that could be causing the neurologic signs. 

In the meantime, as far as post-mortem testing for EPM, “From a financial perspective it’s probably smarter to run the test on targeted PCR than formalin-fixed, because this allows the pathologist to identify a site with active inflammation, which makes it more likely the protozoa will be in that section of the nervous system.” 

Take-Home Message

In summary, Ruby explained that S. neurona is detectable in FFPE tissue in horses with acute and chronic neurologic disease, with and without antiprotozoal treatment, and pathologists rarely detected S. neurona DNA in horses with no histopathologic lesions that would support that diagnosis. 

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