The Harry M. Zweig Memorial Fund for Equine Research

Etiology and Prevention of Equine Serum Hepatitis (Theiler's Disease)

Principal Investigator:           Thomas Divers
Contact Information:         Email:; Phone: 607-253-3226
Project Costs:                   $134,000
Project Period:        1/1/2013-12/31/2014

DiversDr. Thomas Divers

We were asked to consult on an outbreak of acute hepatitis affecting 7 out of 17horses that 47 to 63 days prior to onset of illness had been treated with a single lot Clostridium botulinum antitoxin (BA) of equine origin. Hepatitis was not observed in five other farm horses that received a separate lot of botulinal antitoxin or in 53 farm horses that were not treated with antitoxin. A formal collaboration was established with the Exploratory Virology Group, Novartis Institute of Biomedical Research, Emeryville, CA.  High throughput pyrosequencing was used to demonstrate in the serum of two of the hepatitis cases and in the BA the horses received prior to onset of illness a new member of the family Flaviviridae (the family of human hepatitis C and hepatitis G viruses). The reverse transcriptase – polymerase chain reaction (RT- PCR) was used to test horses for this new equine hepatitis associated virus (EHAV). Fifteen of 16 horses that received the incriminated lot of BA were test positive for the new virus including the 7 horses with acute hepatitis.  Serum from 5 recipients of the lot of botulinal antitoxin not associated with hepatitis, from 15 farm horses that were not treated with BA, and from 20 unrelated horses physically separated by a great distance all were negative for EHAV by RT-PCR. Faculty members of the College of Veterinary Medicine and members of a consortium of approximately 25 academic and private equine clinicians will work collaboratively to accomplish three Specific Aims. SA1. Express cloned EHAV antigen sequences and use recombinant viral proteins for ELISAs to detect EHAV antibodies. SA2.Conduct a prospective case control study and evaluate the association between EHAV infection and new Theiler’s disease cases.  SA3. Using EHAV specific ELISAs and RT-PCR assays conduct serologic surveys of cooperating horse farms across the United States and Canada and measure the EHAV antibodies and nucleic acids in serum and determine the prevalence of EHAV infection.  Discussions have been initiated with Novartis to provide overlapping 1 kb clones of the entire EHAV genome to be used for production of recombinant viral proteins.  Work on SA1 can be initiated as soon as the EHAV clones are made available and useful EHAV ELISAs are anticipated within 8 to 10 months.  The SA2 case control study and the SA3 serologic surveys will begin when the consortium is operational by the end of calendar year 2012.  It is anticipated that one case of Theiler’s disease per year per will be enrolled in the case control study per year with a concluding case enrollment after 18 months of  37 cases. Consortium participants also will arrange for EHAV serologic surveys on 20 farms with approximately 500 adult horses across the United States and Canada.   The collection of clinical data and the analysis of serum should be completed during the first 21 months and a final report prepared and submitted for publication by the end of the proposed period of the study.