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Virus behind hepatitis in horses identified

Overview of a Theiler’s disease outbreak. Twenty-two horses on Farm A suspected of exposure to botulinum toxin were prophylactically treated with i.v. equine antibotulinum toxin hyperimmune plasma. Five horses received antitoxin from one source (gray horses, antitoxin 1), whereas 17 horses received an independently sourced batch (black horses, antitoxin 2). Fifteen horses followed in this study went untreated (white horses, untreated). Within 8 wk of antitoxin administration, 8 horses treated with antitoxin 2 showed signs of acute hepatitis (yellow boxes). All other horses were clinically asymptomatic (no boxes).

Overview of a Theiler’s disease outbreak. Twenty-two horses on Farm A suspected of exposure to botulinum toxin were prophylactically treated with i.v. equine antibotulinum toxin hyperimmune plasma. Five horses received antitoxin from one source (gray horses, antitoxin 1), whereas 17 horses received an independently sourced batch (black horses, antitoxin 2). Fifteen horses followed in this study went untreated (white horses, untreated). Within 8 wk of antitoxin administration, 8 horses treated with antitoxin 2 showed signs of acute hepatitis (yellow boxes). All other horses were clinically asymptomatic (no boxes).

American researchers have identified a novel virus believed to cause a form of hepatitis in horses.

Theiler’s disease is an acute hepatitis in horses and has been known since 1919 but, until now, scientists have not known the causative agent.

Researchers have used genetic sequencing to identify a previously undescribed virus of the Flaviviridae family which they believe is behind the disease.

They have called the virus “Theiler’s disease-associated virus” (TDAV).  Their findings have been published in the Proceedings of the National Academy of Sciences.

They found that the virus shares only 35.3 per cent amino acid identity with its closest known relative.

Theiler’s disease is associated with the administration of equine blood products.

The researchers, from the Novartis Institutes for BioMedical Research in California and the College of Veterinary Medicine at Cornell University in New York, got on the trail of the virus after eight horses developed hepatitis after being injected with an antitoxin to prevent them from developing botulism.

Theiler’s disease was first reported in 1919 by Arnold Theiler, who observed symptoms of liver disease in animals given a vaccine against African horse sickness with a combination of live virus and equine antiserum.

In the ensuing decades, numerous outbreaks of Theiler’s disease have been reported in North America and Europe, typically following the relatively common practice of administering hyperimmune equine plasma or serum to horses exposed to contagious or life-threatening infectious agents, such as Western equine encephalitis virus, Bacillus anthracis, Streptococcus equi, Clostridium perfringens, and equine influenza virus, or toxins such as tetanus.

Horses typically exhibit a rapid onset of acute symptoms, including lethargy, anorexia, and jaundice, as well as an elevation of serum levels of liver enzymes and bilirubin two to three months after receiving blood products. Fever and additional central nervous system signs may also be present.

Postmortem studies of Theiler’s disease cases have identified significant necrosis and degeneration in the liver, identifying this as the major site of pathology. Morbidity rates associated with Theiler’s disease outbreaks vary from slightly more than 1 per cent to as high as 18 per cent.

Among symptomatic horses, Theiler’s disease results in death rates between 50 per cent and 90 per cent.

The association between prior treatment with equine serum or plasma and the appearance of Theiler’s disease has long suggested the presence of a contaminating toxin or infectious agent.

However, until now, numerous experimental studies in both the natural equine host and laboratory animals have failed to convincingly identify an underlying cause.

“We note that although we have discovered TDAV in horses, the natural reservoirs and hosts of this virus are unknown; it could be an exclusively equine virus or an agent introduced into the equine population from another source and amplified there by the practice of transfusion,” the researchers said.

“Further epidemiological work will be required to answer this question.”

 

PNAS Plus – Biological Sciences – Microbiology:
Sanjay Chandriani, Peter Skewes-Cox, Weidong Zhong, Donald E. Ganem, Thomas J. Divers, Anita J. Van Blaricum, Bud C. Tennant, and Amy L. Kistler
Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis
PNAS 2013 ; published ahead of print March 18, 2013, doi:10.1073/pnas.1219217110

The full study can be read online here.

 

 

 

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