Your veterinarian has just examined your wobbly mare and EPM is on the differential diagnosis. The differential diagnosis lists all the possibilities that could be causing the clinical signs. Of course, EPM is an exclusionary diagnosis, meaning other diseases that look like EPM must be ruled out. After taking in the possibility that she could have an active S. neurona infection, you are worried about her fetus. What do we know about the possibility the fetus will get infected?
The clinical examination
Your first action is to get a good neurological exam. The examination is conducted while moving and preferably navigating an incline. The incline makes it more difficult for a weak or neurologic horse to walk. A good history is paramount and don’t forget to talk about medications and supplements. It’s important to discuss medications that horses on the farm receive in case there is cross-contamination.
All of the horse trials conducted in the early 2000’s found that EPM medications were transmitted in the environment. At the end of the study the untreated horses had EPM medication in their system. We investigated and it was the water in communal troughs that became contaminated. There was enough Marquis in one communal water trough we tested to result in sentinel horses having measurable amounts of the drug in their cerebrospinal fluid. At least one company had to re-run their trial at a great loss in time and money. In our studies, it was necessary for untreated cohorts to remain housed in a different field and in another trial, feed and water was restricted when the animals were out of the stalls for free exercise.
The complete history requires a walk about the farm to look for toxins or toxic plants. Your agricultural agent is an available source if your veterinarian is busy or unfamiliar with your farm. Your veterinarian will be looking at your feed and hay for weeds that shipped in from out west. We found hoary alyssum contamination in a hay load that caused several abortions and premature labor in an Ocala breeding farm. Mold has to be considered. A black light examination of the feed may be used to detect mold.
Laboratory tests include a CBC and serum chemistry and some diagnostics. Lab tests are dictated by other diseases in the neighborhood, they include EHV-1, rabies, Lyme, and your vaccination history is important here. Your veterinarian will give you the option of a cerebral spinal fluid analysis. Remember 85% of horses in the United States have antibodies against S. neurona so the useful serological result is a negative test. A negative serum test is good evidence that the horse hasn’t been exposed to S. neurona and other diseases are more likely. Negative tests are hard to come by in the United States.
Transplacental transmission of Toxoplasma gondii
A recent paper from Brazil reported the investigation for the presence of DNA for several protozoa in the placenta and amniotic fluid of mares. They looked for antibodies by indirect fluorescent antibody test, IFAT, in the serum of pregnant mares in the last four months of pregnancy. The researchers concentrated on Toxoplasma gondii, Neospora caninum, and S. neurona. They used polymerase chain reaction (PCR) for detecting the parasite DNA.
Toxoplasma was a no show for DNA or antibodies in all of the horses in the study. That surprised us. We conducted a survey a few years back for toxoplasma antibodies in horse sera and found that 25% of horses we tested did have antibodies. All of the horses we tested were clinically normal. Others found similar data. I believe any test for Toxoplasma would have to consider the virulence of the organism that is used in the testing. Toxo strains vary in virulence. It is intuitive to say some strains are infectious to horses and some aren’t. Someone may investigate equine virulent Toxo in the future. The testing laboratory would need to use the correct strain for horses, until proven otherwise, it is our opinion that strain is a confounding factor.
There is one interesting report of toxoplasmosis in horses and people you should read. The source of the infection was a dusty, indoor arena! The cat is the definitive host for Toxoplasma. The farm cats used the arena as a litter box and the arena dust carried the infections to people and horses. If you are interested in the report, contact us by email and we will send you a copy. Although it would be rare, it is a warning for pregnant women to avoid riding in this type of environment.
Transplacental infection with EPM associated protozoa
The Brazilian researchers found Neospora antibodies in some mares. They also found Neospora DNA in some of the placentas and amniotic fluid samples. It isn’t surprising to read that they detected Neospora in some horses. Vertical transmission, from mother to fetus, is known to occur with this organism, there are published reports in cows. This study qualified that the Neospora was due to the species caninum.
The IFAT used in the study detected antibodies against Sarcocystis sp. and S. neurona DNA was detected by PCR in one placenta. This doesn’t surprise us. In one of our early challenge laboratory studies one of the mares came to us just after breeding. On post-mortem exam this challenged mare was infected with S. neurona and we detected the protozoa by histopathology in the lung of her fetus. Our detecting antibody was specific for S. neurona, we used the same monoclonal antibody that was developed during my thesis work at the University of Florida.
The novel histopath finding was interesting enough for us to conduct some vertical transmission studies in mice. Our results were interesting. If a mouse was already pregnant, the developing fetus was resistant to infection. However, if the mouse was challenged at the time of breeding, there was vertical transmission and the breeding resulted in non-viable embryos. After several experiments we concluded that the period prior to the fetus developing immunocompetence was a risk factor for vertical transmission in mice. The mouse embryo develops immunity at about 10 days. Mice that were already at least 10 days of gestation didn’t transmit the protozoa to the fetus or the fetus didn’t support infection. Viable pups were born.
A horse fetus develops immunocompetence at about 45 days gestation. Because S. neurona circulates in leukocytes, there is opportunity for parasites to contact the fetal circulation from the mothers blood. Extrapolating from our mouse studies, if the window of exposure is prior to 45 days, infection of the fetus is possible. However, if the exposure is after 45-50 days of gestation, we suspect an infection is unlikely to occur.
This work needs to be repeated in horses at various stages of gestation. A laboratory experiment would be very expensive and is unlikely to be conducted. Extrapolation from existing cases, if anyone recognized them, may be illuminating, but the hypothesis would be difficult to prove. Other factors that are not controlled in a non-laboratory study need to be considered. In this type of study considerations are environmental exposure, species of the Sarcocystis in the environment, immune status of the mare at conception, and stage of gestation when clinical signs present.
The mare that entered our study was bred just days prior to entry and the fetus was not detected by palpation. The history was incomplete, and she qualified for the study. She was challenged with a SAG1 strain of S. neurona isolated from a horse with EPM, using our Trojan Horse model. She was challenged within the window of possible fetal infection, prior to 45 days. The challenge resulted in clinical signs in the mare and the fetal tissues harbored detectable protozoa in the lung tissue. No organisms were found in the fetal brain tissues so the fetus didn’t have EPM, it had sarcocystosis.
Some concluding remarks
Your veterinarian can call us to consult if your pregnant mare shows signs of EPM. We want to know if she lives in a positive environment and the serotypes of the S. neurona that are in the environment. If you test 10% of the herd on the farm for serotype specific antibodies the information will give us a good idea of the serotypes present. You already guessed the next question: What day of gestation is she? What are the other considerations on the veterinarians differential diagnosis? Is the horse vaccinated, particularly for EHV-1? And so important, are there any “EPM prevention drugs” being given, in other words are anti-protozoals on the farm. And, has she been treated for EPM in the past?