Co-infections: EPM and Lyme
Paddy: Mr. Photogenic 2011
Paddy is shown here with girlfriend Honey, he wins the most photogenic award. His owner Kim shared a video of this stallion playing gently with yearlings, he’s so kind-he’s truly exceptional. Kim tells us that “Paddy" (JC reg. name - Katahdin) was a genuine herd sire who enjoyed babysitting foals and playing jolly ball tug of war. Bold and athletic, his favorite rides were on the seashore of Assateague Island and more recently learning to jump with his new trainer. His good morning neigh will be missed by all he left behind, disease overtook him in 2011.
Our tests indicated that Paddy had been exposed to S. neurona. Kim also shared with us “I spoke with you by phone a few weeks ago, and my veterinarian enrolled my stallion, "Paddy" in your field trial for EPM. I think he has updated someone with your team already, but, tragically, my stallion had to be euthanized on day 4 of treatment. I know you interpreted the ELISA as an exposure, not an active infection, and offered trauma or possibly Lyme as differential diagnoses. We do live in a Lyme indigenous region. My veterinarian did collect blood for Equine Lyme and Anaplasmosis ELISA that resulted in a positive antibody response.”
Equine granulocytic anaplasmosis is a seasonal, tickborne bacterial disease of horses caused by ticks. Anaplasma targets horse white blood cells, and infection can produce high fever, ataxia, and thrombocytopenia.
“Paddy’s progression of symptoms mimicked a mare that I owned 10 years previously who was successfully treated for EPM, after an EPM diagnosis was confirmed through testing. Although Paddy was much more ataxic at a walk, where her condition was more obvious at the trot and canter. She recovered and is still used for trail riding”.
We shared Kim’s grief and thanked her for letting us use Paddy in our blog to educate others about co-infections. His case is important and illustrative because duel-parasite infections are recognized in horses and other species. We already know that we can have several S. neurona phenotype infections from exposure to opossum feces. The interplay between virulence and growth rate of each Sarcocystis may determine eventual disease status in the horse. But what happens when there are two different pathogens, like a virus, bacteria, or another type of protozoa?
Severity of protozoal encephalitis increases in co-infected animals
A link was found between severe illness and co-infection with Sarcocystis neurona and Toxoplasma gondii in marine mammals that died in the Pacific Northwest. There was a significant association between the co-infections and mortality rate as well as co-infection and severity of protozoal encephalitis in the marine mammals. The sea otter study was conducted by Mike Grigg, NIAID, a part of National Institutes of Health, and the data was published in the open access journal PLoS Neglected Tropical Diseases. He determined that some of these animals harbored the SAG 6 phenotype of S. neurona, a novel discovery and so far (in 2011) the only known cases of SAG 6 infection. We have ample serological evidence of SAG 6 neurona in horses, but because it has never been isolated from a case of EPM, it is possible that the SAG 6 phenotype is not as virulent in the horse, perhaps not able to reach the central nervous system. In sea mammals, SAG 6 S. neurona was highly lethal when they were co-infected with another organism.
Borrelia (Lyme) and Sarcocystis infect horses
Co-infections may also be a factor in horses that have severe protozoal myeloencephalitis. Forty percent of horses that did not survive for the treatment period were co-infected with Borrelia in our exploratory study in 2010. Our study numbers were small for the non-surviving horses and other studies would need to be conducted to reach statistical significance. The bacteria Borrelia burgdorferi is in certain species of ticks and can cause Lyme disease in animals, including horses.
We spoke to Dr. Bettina Wagner, at the time she was the Harry M. Zweig Associate Professor in Equine Health and lead developer of a new test for Lyme in horses and dogs developed by researchers at the College of Veterinary Medicine at Cornell.
"We've offered Lyme disease testing for years," said Bettina Wagner, "but we have recently been able to improve our techniques with the multiplex testing procedure. The new test exceeds its predecessors in accuracy, specificity and analytical sensitivity." The bacteria that cause Lyme disease are particularly difficult to detect, according to Wagner. In humans and horses, they also burrow into the nervous system, in the spine or the brain, causing pain, paralysis or behavioral changes. By the time such clinical signs appear, the bacteria are usually not in circulation anymore.”
The onset of EPM with Lyme disease is rapid, all these animals had profound depression. Despite aggressive treatment the animals were unable to last long enough to identify the infections by laboratory testing. Veterinary intervention was unable to control the infections. They are just too sick to continue therapy. We made no attempt to culture organisms from these animals in our study, we hope that unpublished findings will benefit a few animals by alerting veterinarians to this threat. Animals which are gravely ill with acute onset of signs that live in Borrelia endemic areas would benefit from Lyme disease testing. Although it is unusual, co-infections can exacerbate S. neurona encephalitis in the horse.
Implications for the PNE Field Study
When you consider the signs that are observed with co-infections it is understandable why FDA requires us to do additional testing on the PNE Field Study participants. Lyme is differentiated by region and possible exposure as well as the fever and profound depression. These aren't typical with chronic polyneuritis equi. Vaccination rules out the possibility of some cofounding infections. We test for EHV-1 on all horses that are enrolled into the PNE study because there is one published reference that EHV-1 may be linked to PNE. The idea was the infection had cleared and the inflammation remained, a bystander mechanism.