February 06, 2018

New Parvovirus Discovered within Equine Tetanus Antitoxin

A new equine parvovirus found within equine tetanus antitoxin was associated with serum acute hepatitis, raising concerns abouse the use of equine biological products.
By JoAnna Pendergrass, DVM
Equine serum hepatitis, also known as Theiler’s disease, has a serious and often fatal clinical course.

Previous studies have reported the development of Theiler’s disease after administration of equine serum products, with tetanus antitoxin currently having the most common association with the disease.

A recent report in the Centers for Disease Control and Prevention’s Emerging Infectious Diseases journal detailed the discovery, genetic characterization, and transmissibility of equine parvovirus-hepatitis (EqPV-H)—a new virus associated with equine serum hepatitis.

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Case Study
EqPV-H was discovered when a horse in Nebraska developed clinical signs of liver failure and subsequently died approximately 2 months after receiving prophylactic treatment with tetanus antitoxin. The report’s research team performed genetic analyses on the horse’s serum and liver samples and remaining antitoxin.

The serum and liver samples and antitoxin were first tested for 3 flaviviruses recently discovered in horses: (1) nonprimate hepacivirus (NPHV), which causes temporary liver enzyme elevations; (2) Theiler’s disease-associated virus (TDAV); and (3) equine pegivirus. All samples and antitoxin were negative for these viruses.

Further genetic analyses identified a new virus—EqPV-H—as a genetically distinct parvovirus within the Copiparvovirus genus. Phylogenetic analysis determined that, within this genus, EqPV-H is most closely related to bovine and porcine parvoviruses and less closely related to horse parvovirus-CSF, indicating that EqPV-H and horse parvovirus-CSF had different evolutionary paths.

Experimental Infection
To confirm EqPV-H transmission through contaminated tetanus antitoxin, the researchers experimentally infected 2 healthy adult mares with EqPV-H-PCR-positive tetanus antitoxin. Each week thereafter for approximately 4 months, the following tests were performed:
  • Serum biochemistry
  • PCR testing for NPHV, TDAV, and EqPH-V
  • Serology for EqPV-H antibodies

Both horses began testing positive for EqPV-H approximately 48 days post infection (dpi), with viremia peaking between 81 and 96 dpi. At the study’s termination, both horses were still EqPV-H positive. They remained negative for NPHV and TDAV throughout the study. EqPV-H antibodies first appeared at about 90 dpi in both horses.

Serum biochemical evidence of acute hepatitis first became evident in both horses between days 82 and 96 dpi, with elevated levels of bile acids, total bilirubin, aspartate aminotransferase, sorbital dehydrogenase, and γ-glutamyltransferase.

Liver biopsies taken from both horses also demonstrated acute hepatitis, with such abnormalities as hepatocyte necrosis and lymphocytic lobular atrophy.

Infection Prevalence
The researchers tested 100 horse serum samples of convenience submitted to a veterinary diagnostic laboratory; the samples were from horses without serum biochemical evidence of hepatitis. Only 13 samples were PCR-positive for EqPV-H (indicating viremia) and had circulating EqPV-H IgG, suggesting “that most horses that become in­fected with EqPV-H do not develop clinical disease,” the researchers wrote.

Interestingly, 2 horses that were PCR-negative for EqPV-H were seropositive, indicating viral clearance. Genetic analyses revealed low genetic variance between the samples.

Implications
Study results suggest an association between EqPV-H and Theiler’s disease in horses, raising concern for the presence of this virus in equine biologics. Although heat treatment of commercial tetanus antitoxin inactivates heat-labile viruses, animal parvoviruses are highly resistant to heat inactivation, increasing the possibility of EqPV-H transmission through the antitoxin.

For the future, the researchers proposed testing horses from varying geographic areas to determine EqPV-H’s true prevalence and genetic diversity. Also, additional testing is necessary to determine why not all horses infected with EqPV-H develop serious and often fatal hepatitis.

 
Dr. JoAnna Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.

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