Research developments newly reported for Sarcocystis neurona may impact horse owners their veterinarians. A novel genotype XIII was reported by Barbosa et al in the International Journal for Parasitology (2015). This novel genotype is a sea mammal-virulent SAG 1 strain supporting SAG 1 and 5 antigen types dominate animal disease. This strain is vertically transmitted, from the mother to the fetus indicating S. neurona is more like than unlike other pathogenic protozoa. Our pending publications, reviewed in our last two blogs, report new tests for horses with recurrent or residual signs of EPM that seek to clarify the role of inflammation in suspect-EPM horses. The bottom line is that the key to maintaining a healthy horse is management through testing and examinations and understanding the pathogenesis of disease.
Sarcocystis neurona possesses one of six major surface antigen genes, SAG’s 1-6, on its outer surface. The horse makes antibodies to these SAG’s and the antibodies are detected in the serum by ELISA testing. Minor differences within the SAG genes allows classification into genotypes, or antigen types. For example a SAG 1 S. neurona may be antigen type II or XIII. The horse can only distinguish between SAG’s 1, 5, or 6 (serotypes) not antigen types. The SAG’s 2, 3, and 4 are genetically variable between serotypes, are present in all Sarcocystis, and allow molecular biologist to examine differences between SAG genes. Geneticists look at allelic variation within the SAG genes and that allows them to sub-classify S. neurona into genotypes or antigen types.
We developed three SAG specific ELISA tests based on recombinant SAG 1, 5, and 6, the strains that infect horses . The specificity of these tests allows us to distinguish between serotypes by the antibodies made in response to infection. The majority of all disease caused by S. neurona in animals is due to SAG 1 and SAG 5 serotypes. There may be virulence differences between the S. neurona SAG 1: antigen type II or XIII (discussed in Barbosa’s paper). What is clinically relevant in the sick horse is recognizing the serotype. Measuring specific antibodies allows the veterinarian to identify resistant infections, determine the response to treatment, and distinguish relapse versus re-infection.
Our newest work identifies horses that have chronic inflammation. Inflammatory responses cause the clinical signs often associated with EPM. Some horses won’t respond to antiprotozoal agents because the protozoa are gone. A frustrating clinical presentation is identifiable with our new serum testing, MPP and IL6 ELISA’s. Our approach to managing these horses has not changed, we still measure SAG antibodies pre- and post-treatment. We assess the horses by gait score before and after treatment. We monitor the CRP serum concentration. What has changed is that we can identify horses that will relapse and give the veterinarian an explanation why and a management program.
It is well known that equine serum samples show variation in reactivity to different surface antigens of S. neurona. The most useful clinical point: it is not the level of antibody (titer) present in a horse’s serum that is important, but noting that the levels rise with duration of infection. Another general rule is that the first experience with infection (naïve horse) will induce antibody production. The levels are minimal and short lived (8 weeks or so). A horse experienced with infections will get and maintain a higher antibody level up to 5 months in some animals. Management of EPM cases requires multiple serum analysis. A single point test can’t decipher a new infection or a relapse. Multiple tests can suggest it the animal has naive infection or chronic exposure. The horse with chronic exposure is more likely to experience abnormal immune responses that may look like EPM but really suffer from chronic polyneuritis. It is important to distinguish these infections because the clinical management differs.
There is a report for a new trivalent SAG chimera ELISA test for efficient detection of antibodies against S. neurona . This is an ELISA test that seeks to reduce the time, materials, and cost associated with running multiple ELISA’s using SAG 2, 4/3. The diagnostic protocol involves using the the SAG ELISA to determine a consensus serum-to-CSF ratio, ratios less than 100 suggest that antibodies against S. neurona are being produced in the CNS and therefore parasites are suspected in the CNS. Diagnosis of EPM based on CSF results is still confounded by normal passive transfer of antibodies across the blood-brain barrier. The changes to detection of SAG 2, 4/3 antibodies by the third generation test don’t identify the issues concerning non-specific testing, it can’t discern serotype, doesn’t indicate a treatment failure due to strain resistance, or point the clinician in the direction of inflammation when parasites aren’t there. It remains to be seen if the reduction in costs for time and materials will transfer to the client.
The most exciting new information is in the Barbosa paper. They report vertical transmission in S. neurona in a sea lion, a harbor porpoise, five harbor seals, and a pygmy sperm whale. We suspected and reported S. neurona in the lung tissue of a fetus from a mare experimentally infected with S. neurona in 2004. We suggest that there is a unique window of opportunity for fetal infection, before the fetus gains cellular immunity. The observations of Barbosa and sea mammal infections may change the opinion that S. neurona is not vertically transmitted in horses (Dubey).
The possibility that mares can transmit infections to the fetus may stimulate management changes on farms with a high incidence of EPM. It would be a very rare condition and the veterinarian is the best source to analyze risks on a case-by-case basis.
Give us a call if you have questions or concerns about EPM . We outline management protocols for horses as part of our consulting service. We haven’t seen any new evidence that prods us to change our approach to the diagnosis of sarcocystosis or inflammatory mediated neuropathy. We advise multiple exams, even in a recovered horse, once healthy let’s keep them that way! We are committed to testing for SAG 1, 5, and 6 in independent ELISA tests, we won’t combine our three tests for convenience or price. Confirming the presence of inflammation and distinguishing peripheral from central neuropathy are current goals.
We are committed to developing diagnostic tests and effective treatments for parasitic disease.