Borna disease

Borna disease is an infectious neurological syndrome^[1] of warm-blooded animals, caused by Borna disease virus, which causes abnormal behaviour and fatality. The causative agent of Borna disease, Borna disease virus (BDV) is a neurotropic virus and is a member of the Bornaviridae family within the Mononegavirales order.

Although the Borna disease virus is mainly seen as the causative agent of borna disease in horses and other animals, it also infects humans and is therefore considered to be a zoonotic agent. The role of BDV in human illness is controversial and it is yet to be established whether BDV causes any overt disease in humans. However, correlative evidence exists linking BDV infection with neuropsychiatric disorders such as bipolar disorder.^[2]

Avian Bornaviruses (ABV), a group of related viruses, have recently been reported, yet not proven, as the cause of Proventricular Dilatation Disease (PDD), a disease of pet parrots. The use of a 'positive' brain cell culture containing ABV to inoculate another psittacine (parrot) bird resulted in the inoculated bird's death and subsequent histopathological diagnosis of PDD (mononuclear infiltrative ganglioneuritis. Earlier research with purified inoculant of ABV(while did result in the death of parrots) did not reproduce histopathological changes associated with PDD.

Sadly, there have been several parrots tested positive for ABV without clinical signs of PDD that were prematurely euthanized and revealed no such histopathological tissue changes. Additionally some parrots with clinical signs of PDD have been tested negative for ABV and have later died within weeks of testing. These parrots that had clinical signs of PDD, that tested negative for ABV, were then subsequently diagnosed with PDD on histopathology. In summary Avian Bornavirus should not be referred to the cause of Proventricultar Dilation Disease in psittacines, it is of questionable value to test any psittacine bird for ABV, and the only definitive diagnosis of a live parrot for PDD is a crop biopsy with histopathology. Of great importance is that any parrot tested positive for ABV should be retested 90 days later, and persistently ABV positive parrots should be considered as immunocomprimised. PDD is one yet not the only such disease possibly associated with an immunocomprised state.

Thankfully, many parrots with signs of PDD have made apparently full recovery with the veterinary use of non-steroidal anti-inflammatory drugs (NSAID's), yet should be considered a potential infective source of PDD for other parrots.

Epidemiology

Vectors

The mode of transmission of BDV is unclear but probably occurs through intranasal exposure to contaminated saliva or nasal secretions. Following infection, individuals may develop Borna disease, or may remain subclinical, possibly acting as a carrier of the virus.

Animals

Borna virus appears to have a wide host range, having been detected in horses, cattle, sheep, dogs and foxes. In 1995, the virus was isolated from cats suffering from a "staggering disease" in Sweden. Since that time, the virus has also been detected in cats in Japan and Britain.

Borna virus has been detected in humans, and researchers have presented evidence connecting these infections with psychiatric disorders.^[3][4][5]

Experimental infection of rats has been demonstrated to lead to learning impairments and altered social behaviour. The virus appears to be distributed primarily in the limbic system of the brain, including the hippocampus and entorhinal cortex. These areas of the brain are considered to be of importance in emotion.

Originally identified in sheep and horses^[6] in Europe, it has since been found to occur in a wide range of warm-blooded animals including birds, cattle, cats^[7] and primates and has been found in animals in Europe, Asia, Africa and North America. The name is derived from the town of Borna in Saxony, Germany, which suffered an epidemic of the disease in horses in 1885.

Borna disease in sheep and horses arises after a four week incubation period followed by the development of immune-mediated meningitis and encephalomyelitis. Clinical manifestations vary but may include excited or depressed behaviour, ataxia, ocular disorders and abnormal posture and movement. Mortality rates are 80-100% in horses and greater than 50% in sheep.

Borna disease in the horse gives rise to signs like:

• Unusual posture, gait and ear positions
• Movement Disturbances (principally ataxia or excess movement)

History

The first antibodies to Borna virus in humans were discovered in the mid-1980s. Since then, there have been conflicting results from various studies in regards to whether an association exists between the agent and clinical disease. Antibodies to Borna virus, which indicate prior infection, and Borna virus antigen have also been detected in blood donors.

Psychiatric disease

There is some evidence that there may be a relationship between Borna virus infection and psychiatric disease.^[3][4]

In 1990, Janice E. Clements and colleagues reported in the journal Science that antibodies to a protein encoded by the Borna virus genome are found in the blood of patients with behavioral disorders.^[5] In the early 1990s, researchers in Germany, America, and Japan conducted an investigation of 5000 patients with psychiatric disorders and 1000 controls, in which a significantly higher percentage of patients than controls were positive for BDV antibodies.^[5] Subsequent studies have also presented evidence for an association between Borna and human psychiatric disorders.^[8][9][10] However, not all researchers consider the link between Borna virus and human psychiatric disease to be conclusively proven. A recent study found no Borna virus antibodies in 62 patients with the deficit form of schizophrenia.^[11]

Additional evidence for a role of Borna virus in psychiatric disorders comes from reports that the drug amantadine, which is used to treat influenza infections, has had some success in treating depression and clearing Borna infection.^[12] Counter-claims state that Borna virus infections are not cleared by amantadine.^{[citation needed]} The issue is further complicated by the fact that amantadine is also used in the treatment of Parkinson's disease and may have direct effects on the nervous system.

References