UPDATED: AUGUST 7, 2020
There is a disease syndrome called “serum hepatitis” that affects horses. This is a very rare event and is linked to the administration of equine blood origin products. About 20% of horses with idiopathic acute hepatic disease (IAHD) show clinical signs of liver failure (anorexia, lethargy, jaundice) within 4 – 10 weeks after receiving an equine origin biologic – hence the name “serum” hepatitis.1 One of the most common equine serum origin products used in the field is Tetanus Antitoxin. Many other equine blood origin products, including equine plasma products and equine stem cells, have also been linked to serum hepatitis.2,3,4,5
Serum hepatitis is also called Theiler’s disease, named after the veterinarian who first described it in 1919, so the link between equine blood origin products and hepatitis has been well documented for over 100 years.6 As mentioned earlier, it is a very rare event (incidence is ~ 1:500,000 doses of TAT sold, based on Colorado Serum data), but “outbreaks”1,4 have been reported every few years with multiple horses in the same and sometimes different geographic areas involved. Some horses will develop hepatitis having never received an equine serum product before.1,10 The incidence of fulminant hepatitis among horses receiving antiserum in outbreaks of Theiler’s disease has been reported to be 1.4%-2.2%.1,7 Some toxic plants, moldy corn and blue-green algae can also cause hepatitis.1 Without a definitive infectious agent the most plausible causative explanation/theory is a type III hypersensitivity (allergic) reaction.1,9 Attempts to find a causative infectious agent have been unsuccessful for decades, until possibly recently, but Koch’s postulates (four criteria designed to establish a causative relationship between a microbe and a disease) still have not been met.
With the advent of new diagnostic technology, research in the past 10 years has shown a possible viral cause, at least in some cases of equine hepatitis; a recently discovered equine parvo virus (EqPV) has been implicated.7 Screening of healthy horses by PCR testing shows that this virus is very common in the equine population7, usually causing no disease or clinical signs. Very rarely, however, it appears that this virus is associated with hepatitis in horses. One of the remaining hurdles to confirm whether or not equine serum or plasma products could be a potential source for the transmission of live EqPV to recipient horses is the inability to isolate live EqPV.7 Currently, there is no other test for the EqPV other than PCR and this test detects genetic material and does not differentiate between live and dead virus. In the case of licensed equine serum products like Tetanus Antitoxin the serum is pasteurized and contains thimerosal and phenol preservatives to help mitigate bacterial and viral contaminants. In the case of phenol, our equine serum products contain phenol levels above what has been shown to kill many viruses including similar parvo viruses that can be isolated in tissue culture (canine parvovirus).8 Colorado Serum Company has also demonstrated this in our processed equine serum – showing that our processing steps do kill porcine parvo virus in experimentally spiked serum samples. In the coming months, USDA/CVB will require all equine serum and plasma donors used for licensed equine serum and plasma products to be screened and test negative for EqPV. All final product has to be tested as well and unfortunately until an assay can be developed to detect live EqPV all of this testing will have to be done with the PCR assay. Besides being a very rare cause of disease in horses it should also be noted that EqPV does not cause disease in other species on the labels for equine serum products like cattle, sheep, goats and pigs. Until it can be proven that live EqPV is being transmitted in licensed equine serum products and causing 100% of all equine serum hepatitis cases another plausible explanation/theory continues to include a type III hypersensitivity reaction mentioned before. This is a type of allergic reaction where antigen-antibody complexes form in the liver which results in hepatitis. This disease could also be multi-factorial involving EqPV, antibodies to EqPV or some other inherent protein in equine serum involving a hypersensitivity reaction or some other immune-mediated mechanism like what is seen in humans with hepatitis B.5 Regardless of the cause, the fact remains that serum hepatitis in horses is a very rare event, but it does have a high mortality rate in horses that develop fulminant hepatitis.7 Horses that do recover seem to make a complete recovery with no persistent liver disease.4,7 Because of the link between equine blood products and this disease there has been a warning regarding serum hepatitis on every equine serum product made for horses by Colorado Serum Company for many years.
A prudent measure to avoid the risk of serum hepatitis is to vaccinate your horse with tetanus toxoid on a regular basis. By vaccinating your horse as a foal at 5 or 6 months of age with a booster 30 days later, followed by annual boosters (with pregnant mares getting their annual booster 2 – 4 weeks before foaling) the need to use tetanus antitoxin is eliminated. In situations when a vaccinated horse (vaccinated = 12 months prior) receives a wound then all that is necessary is a tetanus toxoid booster, along with antibiotics. Tetanus antitoxin should be used (along with antibiotics) in wounded horses that have no previous history of tetanus toxoid vaccination, or are overdue (> 12 months) for a tetanus toxoid vaccination, or in cases of treatment for tetanus disease, in which case your veterinarian should be treating the animal with adjunctive therapy and very large doses of tetanus antitoxin. The risk of tetanus in unvaccinated injured horses is still much greater than the risk of serum hepatitis.
Tetanus antitoxin is usually a very safe biologic that has its place in the equine world (and for other species) but its use, like all biologics, is not without risk and serum hepatitis is a unique and very rare risk to horses associated with equine serum products. For this reason it is wise for horse owners and veterinarians to be aware of these risk factors when using biologics and to understand when tetanus antitoxin is indicated vs. a tetanus toxoid booster. Colorado Serum Company also has an economical single fraction tetanus toxoid.