Clinical diagnosis is not difficult if there is a documented, relevant history of exposure and subsequent compatible clinical signs or symptoms. However, because an exposure history may be lacking, rabies should be considered in any acute, unexplained neurologic disease of suspected viral origin that rapidly progresses to coma and death. Routine diagnosis is established by standard laboratory tests for specific virus isolates, Ag, or nucleic acids (Hanlon et al., 1999).
• Antigen detection
Postmortem diagnosis should be performed on CNS specimens, especially the brain stem, hippocampus, and cerebellum (Tepsumethanon et al., 1997). FA test and the immunohistochemical (IHC) technique are sensitive and specific methods for detecting virus Ag. Abs, particularly those that recognize epitopes of the N protein, is useful because they provide consistently reliable results, even if the tissues have been fixed with formalin or embedded in paraffin (Warner et al., 1997).
Examination of skin biopsies from the face or hair-covered occipital portions of the neck for virus Ag is a rapid method to diagnose human rabies before death. Rabies virus can be isolated from saliva by direct intracerebral inoculation into mice or by infection of neuroblastoma cells. FA examinations of corneal impressions may also occasionally lead to the diagnosis of human rabies (Koprowski, 1996).
• Molecular detection
RT-PCR has been used to amplify and sequence parts of the virus genome directly from brain, saliva, and other affected tissues (Smith, 1999). This not only allows detection of rabies virus specific RNA but also permits insights into the identity of the virus variant by genetic sequencing. Detection of virus nucleic acid in serum late in the clinical course can be diagnostic for rabies, if the patient has not been previously vaccinated (Noah et al., 1998).
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