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detection of the Borna disease virus relating them to the epidemiology.
The first cases of Borna disease were described in the 17-19th century in Southern Germany. It was discovered to be a fatal disease affecting the neurological systems of horses and sheep, (Ludwig et al., 1985; Durrwald, 1993) causing behavioral and neurological symptoms. It was proven to be caused by a 2003]
Today it is being realized that the scope of the disease is not limited to just a few countries as was previously believed but encompassed the world. Also it was realized that far from affecting just horses and sheep as was originally thought virus, the Borna Disease Virus (BDV) in the early 1900's by Zwick and his team in Giessen Germany. [Author not available, it in fact affected other animals and even human beings.[Staeheli, Sauder; Schwemmle, et al., 2000]
Research into the epidemiology and pathogenesis of the BDV is impeded however by a lack of universally accepted standard for its detection, especially in humans. Many different techniques are available and used, including indirect immunofluorescence assay (IFA), Western immunoblot (WB), anti-BDV antibody detection, radioimmunoprecipitation, enzyme-linked immnosorbent assay (ELISA), RT-PCR and very rarely direct isolation of the virus. None however are considered to be completely reliable and valid.[Diagnostic Methods In Virology, 2003,Nakamura et al. 2000] The sensitivity and selectivity of these assays are under suspicion due to the various results obtained in the same population when different methods are used. [Author not available 2003] This also raises difficulties during epidemiological studies.
This paper is an attempt to cover in detail the various methods used to detect the BDV virus and analyze their efficiency in doing so. This will be done with reference to the epidemiology of the virus that is changing significantly and speedily with the use of the analytical techniques. An attempt is also made to compare these processes and give suggestions for future research in the light of modern day studies.
About the Disease
The Borna Disease and its symptomology has been recognized for almost two centuries now but it was only after the isolation of its etiologic factor, the Borna Disease Virus, that any scientific research into the actual pathogenesis, transmission and management of the disease could be done.
It was found that the Borna disease virus (BDV) was a nonsegmented, enveloped, negative strand RNA virus that had a tropism for limbic and dopamine circuitry of the brain, in particular the hypothalamus. [Author not available 2003] The virus also showed special replication properties being highly genetically stable in its natural host, the horse. [Diagnostic Methods In Virology, 2003] It is thought that the disease process is not induced directly by the replication of the virus; rather it is the virus-induced T-cell mediated immune reaction that produces the pathology. This has been concluded through studies in the Lewis rat, and the discovery of BDV reactive antibodies in the sera of patients with neuropsychiatric disorders. [Diagnostic Methods In Virology, 2003]
Borna Disease is a disseminated non-purulent meningo-encephalomyelitis that infiltrates mononuclear cells (Jurgen 1997, Schizophrenia and Borna Disease Virus as a Zoonosis?, 2000) and polio encephalomyelitis especially affecting the gray matter of the cerebrum and the brain stem (Schizophrenia and Borna Disease Virus as a Zoonosis? 2000). [Diagnostic Methods In Virology, 2003] Clinically it manifests in horses as behavioral changes [Durrwald & Ludwig, 1997] resembling human psychiatric diseases including bipolar disorder, schizophrenia, and autism. [Author not available 2003]
Transmission of the BDV is thought to be through various routes including, salival, nasal, or conjunctival secretions as BDV-specific RNA has been found in all of these. (Schwemmle, 2001, Hagiwara, 1998, Hagiwara 1997) Small quantities have also been found in the feces and urine of infected animals. [Nakamura et al. 2000] It is either through direct contact with these secretions or by contaminated food and water that the virus can be transmitted. Experimentally, the BDV virus has been administered intracerebrally, intraocularly, intranasally and intramuscularly. The virus however has been found to be not very infectious, [Nakamura et al. 2000] though it can recur in those animals that survive the acute attack, especially after stress. (Jurgen 1997)[Diagnostic Methods In Virology, 2003]
The incubation period of the BDV in horses is thought to be about four weeks; [Diagnostic Methods In Virology, 2003] the clinical illness lasting for about 1-3 weeks with neurological signs such as ataxia, depression, circular movement, standing in awkward positions, collapsing, running into obstacles, and paralysis, during the acute phase. [Diagnostic Methods In Virology, 2003] The mortality rates for diseased horses are high, 80% to 100% (Jurgen 1997).
As yet, a definite reservoir for the virus has not been discovered but suspicion through scientific study has fallen on various rodents, seropositive horses with subclinical infections, and even insects due to the seasonal characteristic of Borna Disease epidemics. (Hagiwara 1997)[Diagnostic Methods In Virology, 2003] BDV is more common in some years than in others and the number of documented infections increases in the spring and early summer. [Diagnostic Methods In Virology, 2003]
That the BDV may have a larger geographical and host range than previously believed is being proven by epizootiology studies in animals and epidemiology in human beings. [Diagnostic Methods In Virology, 2003] This research has shown Borna Disease to be a widespread zoonosis and that BDV or a similar virus can also infect human beings. [Diagnostic Methods In Virology, 2003] These conclusions have been arrived at through results of seroepidemiological studies, preliminary data from studies on the isolation of BDV from the CSF and the detection of BDV-specific antigen and BDV-RNA in the human brain. [Diagnostic Methods In Virology, 2003]
Most of the cases of the Borna Disease in animals have been discovered and described in Central Europe, especially in Germany and Switzerland. Liechtenstein (Weissenbck et al., 1998 b; Caplazi et al., 1999). Conclusive evidence to support its presence in other countries has not yet been obtained. [Diagnostic Methods In Virology, 2003] Natural infections however have been documented in North America, East Africa and parts of Asia (including Japan, Israel, Thailand and Taiwan). BDV-specific antibodies were found in horses in several European countries, Israel (Hagiwara, 1998, Hagiwara 1997), Japan (Hausmann, 2001), Iran (Durrwald, 1993), and the United States.[Diagnostic Methods In Virology, 2003] It is seen that BDV antibodies are found in otherwise clinically healthy animals, the natural infections remaining asymptomatic, thus requiring a high index of suspicion for detection. [Diagnostic Methods In Virology, 2003] Using the various techniques for virological studies available and being evolved the scope of this disease could be found to be much larger than believed.
Natural infections have been detected in other Equidae such as, donkeys (Zimmermann et al., 1994; Durrwald, 1993; Caplazi et al., 1999), goats (Caplazi et al., 1999) and cattle (Caplazi et al., 1994; Bode et al., 1994 b) to a certain extent. Some of these are cases detected on farms in areas of Germany where BD is not endemic in horses and sheep (Bode et al., 1994 b). BDV antigen and virus have been detected in the CNS of two rabbits with neurological symptoms. Ruminants, rabbits, (Metzler et al., 1978) cats, and ostriches have also been found to be hosts while it has been seen that non-human primates can be exogenously infected. Recently BDV antigen and RNA has been shown in the brain of a dog with severe CNS inflammation and neurological disease in Austria (Weissenbck et al., 1998 a).
That BDV may be involved in causing 'staggering disease' in cats is supported by initial data showing that a high percentage (44%) of Swedish cats suffering from this encephalitic disease had serum antibodies to BDV (Lundgren et al., 1993; Lundgren & Ludwig, 1993). According to analytical studies viral markers shown to be low in the brains of only three out of 24 diseased cats (Lundgren et al., 1995 a, b). Cats with Staggering Disease in Austria had no detectable levels of BDV markers in the CNS (Nowotny & Weissenbck, 1995).
A study done in Sweden (Berg et al., 2000) described a free-ranging lynx with non-suppurative meningoencephalitis showing similarities to Borna disease. Immunohistochemistry showed that the astrocytes from the lynx's brain stained positive for BDV. [Staeheli 2000] In contrast a RT-nested PCR performed on a sequence of a BDV p24 fragment from the same brain tissue differed by more than 2% from known BDV strains. This underlines the observation emphasizes the idea that the host range of BDV is wider than previously thought. [Staeheli. et al. 2000]
BDV is also considered to be genetically invariable forming a single type in the genus Bornavirus of the family Bornaviridae. This makes detection of the virus difficult as does the low levels of viral load found in diseased cases. [Author not available 2003] The virus exists as BDV-specific circulating immune complexes during the chronic phase of the disease, which impedes the detection of viral antibodies. [Author not available 2003] Scientists also doubt the reliability of using antigens from strains of BDV found in only in animals and not in humans. They have an…[continue]
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5% while 70.5% took Aspirin within six hours after reaching hospital and 76.5% of patients admitted in the NICVD were receiving Aspirin therapy." (Jaiwa, 2006, p.1) Jaiwa reports a more recent study that states findings that out of 52 patients with chest pain only 13 patients or 25% of the 52 received aspirin. The stated reason for not giving aspirin to the other 39 patients included that "chest pain was not