Toxoplasmosis is a disease caused by Toxoplasma gondii , Toxo infects most mammals and birds. Cats (the definitive host) shed the infective material making cat litter a risk factor for people and other animals! In horses, toxoplasmosis is usually asymptomatic, thus the disease is considered subclinical. Cysts form in horse tissues and antibodies are found in the serum from this chronic, subclinical infection. The seroprevalence in horses in the United States varies widely and is reported to be between 0 and 90%! Risk factors for horses include water contaminated with cat litter or feces.
The biology of Toxo makes the tests that are used in studies that detect antibodies against Toxo important. Some strains of Toxo are more infectious than others (virulent strains), and some strains don't cause disease at all. Toxo is a protozoa that can be lethal in some animals (a mouse for example) but the same strain isn’t damaging to another species--that makes the selection of strains used in experiments and diagnostics important.
It is generally accepted that horses are less sensitive to the pathological effects of Toxo infections. In the United States, the best guess for the number of horses in the general population that are subclinically infected with Toxo is between 12-14%. That number was much higher in a group of horses studied in California-- about 25% of the healthy horses in that study were seropositive. The California study examined neurologic horses, those with clinical disease, and showed that they were more likely to be seropositive to Toxo when the sick group was compared to non-neurologic, or healthy horses. These results beg the question, are co-infections a risk factor for EPM in horses?
Marine mammals infected with both S. neurona (the agent that causes EPM in horses) and Toxo were associated with an increased severity of infection. Co-infections were bad for these marine animals. When horses in the Eastern United States were evaluated for subclinical infections of Toxo and protozoal myeloencephalitis over a six-year period, co-infections were not found. These data indicate that horses seropositive T. gondii antibodies didn’t have an increase in clinical EPM. The study made these conclusions looking at the organisms S. neurona and N. hughesi, the protozoans associated with EPM. Subclinical S. neurona sarcocystosis (seropositive, healthy horses) is most common--antibodies against S. neurona are found in more than 80% of horses, yet less than 1% of the horse population is diagnosed with EPM. Neospora hughesi is less common, 34% of healthy horses have Neospora antibodies and of those perhaps 2% have EPM.
There could be a relationship between other protozoa that infect horses; the first on our list is S. fayeri. Sarcocystis fayeri was more common in horses with neuromuscular disease (when compared to normal horses) as shown in two studies. These studies didn’t show that subclinical S. fayeri facilitates EPM (caused by S. neurona) but, EPM was more prevalent in horses that had equine muscular sarcocystosis. Another interesting finding was that statistically, horses with sarcocystosis were more likely to have an elevated C-reactive protein (CRP). Interestingly, it was reported that horses seropositive for Toxo have a higher incidence of pro-inflammatory cytokines and CRP values.
When you ask us what can sustain an elevated CRP in a healthy horse we will give you a list that includes encysted small strongyle larvae, gastric and hind-gut ulcer disease, equine muscular sarcocystosis, and subclinical Toxo. Protozoa can keep pro-inflammatory cytokines active and that makes subclinical inflammation chronic in horses and chronic inflammation can produce disease.
What will it take to develop a useful diagnostic test for Toxo in horses? First, a model of disease. Koch’s postulates must be completed. Linking disease to the infection is important, not just detecting antibodies that were made in response to subclinical infections that didn't progress to disease. Experimentally inducing toxoplasmosis hasn’t been accomplished in horses. It is more complicated that it appears on the surface because Toxo shows strain-related virulence differences in hosts.
It would be easiest to find a horse with acute, clinical toxoplasmosis and isolate the organism—that has not been done yet. As prevalent as Toxo is, one wonders why. An organism isolated from a clinically ill horse could be used to infect horses, validate the model, and answer questions about species susceptibility. The available virulent mice strains or strains isolated from humans may not be useful strains to infect horses or used for diagnostics. We wonder if there is a need for detecting Toxo in horses because, as mentioned above, in a 6-year retrospective study no Toxo infections were related to disease in horses.
However, determining that chronic inflammation is due to Toxo may be important in polyneuritis equi. There are breadcrumbs that lead us in that direction, but as yet no hard evidence. We’ll get back to you after we develop a model for toxoplasmosis in horses, followed by investigation of the statistical significance in various equine populations, diseased and healthy.