Sulphadiazine and pyrimethamine are used in combination to treat equine protozoal myeloencephalitis (EPM). These drugs interfere with folic acid (folate) metabolism, a vitamin essential for survival of the causative protozoon Sarcocystis neurona. In human patients, these drugs can cause folate deficiency. Signs of deficiency include bone marrow suppression and ulcerations of the tongue (glossitis). Supplementation with folate would seem reasonable, but there is evidence that this causes a worsening of the folate deficiency. Recently, researchers from The Ohio State University published a case report describing a mare with paradoxical folate deficiency.

The 6-year old mare was diagnosed with EPM and treated with sulphadiazine and pyrimethamine for nine months, along with a folate supplement. Upon admission to the university, she had an acute episode of dysphagia (difficulty swallowing). She was found to have severe glossitis. Blood work and a bone marrow biopsy revealed bone marrow suppression with resulting anemia and low white blood cell count (leukopenia) as well as folate deficiency. The mare was taken off the EPM medications and folate supplement. Later, she was treated with an intravenous dose of folate, and within days she was significantly improved. When she returned two months later for follow-up, her neurological problems had improved and her blood work was normal.

Folate is available in different forms, some of which require activation in the body. Sulphadiazine and pyrimethamine prevent activation, so folate supplements are often given in the activated form. Unfortunately, this can simply feed the protozoa instead of correcting the deficiency in the horse. Therefore, supplementation with folate is not recommended for horses being treated for EPM.

Piercy, R.J.; Hinchcliff, K.W.; Reed, S.M. Equine Veterinary Journal, 34 (3), 311-316, 2002