The history of Theiler's disease and the search for its aetiology.

Theiler's disease (serum hepatitis) may occur in outbreaks or as single cases of acute hepatitis and is often associated with prior administration of equine-origin biologics approximately 4-10 weeks before the onset of clinical signs. Cases have also been described without any prior administration of blood products. The clinical disease has a low morbidity but high mortality and only adult horses are affected. The course of the disease is short, with horses either dying or completely recovering in a few days. Pathology in affected horses is predominantly centrilobular hepatocyte necrosis with mononuclear cell infiltration of the lesser affected periportal regions of the liver. Subclinical cases of the disease also occur. Based on the epidemiology and pathology of the disease, a viral cause, similar to hepatitis B in humans, has long been suspected. This paper reviews both historical and recent findings on Theiler's disease. Reported epidemics of Theiler's disease in the early 1900s are reviewed, along with their similarities to outbreaks of serum hepatitis in humans following yellow fever virus vaccinations in the 1930s and 1940s. Recent metagenomics-based studies to determine the aetiology of Theiler's disease are discussed, along with both clinical and experimental findings supporting equine parvovirus-hepatitis (EqPV-H) as the likely cause of this 100-year-old disease.