To date, there are no tests available to diagnose human rabies infection ante-mortem, or before the onset of clinical disease. However, rabies should be included in the differential diagnosis of all patients who present with unexplained, acute, progressive viral encephalitis, even in areas where the disease is not endemic.

WHO defines a clinical case of rabies as a subject presenting with an acute neurological syndrome (i.e. encephalitis) dominated by forms of hyperactivity (i.e. furious rabies) or paralytic syndromes (i.e. dumb rabies), progressing towards coma and death, usually by cardiac or respiratory failure, typically within 7-10 days after the first sign, if no intensive care is instituted.

As diagnosis based on clinical ground alone is difficult and often unreliable; it is recommended to confirm a clinical case of rabies through the use of laboratory-based techniques. For post mortem diagnosis, the gold-standard diagnostic technique is to detect rabies virus antigen in infected tissues, preferably brain smears or touch impressions collected from a biopsy, by fluorescent antibody test (FAT). FAT is recommended by WHO and in 95-99% of cases, gives reliable results on fresh specimens within a few hours. Other methods for detection of lyssavirus antigens such as direct rapid immunohistochemistry tests are proven to have sensitivity and specificity comparable to the FAT. WHO recommends further development of direct rapid immunohistochemistry tests as an alternative to the FAT for improved decentralized laboratory-based surveillance in endemic areas.

Ante-mortem diagnosis, or diagnosis of rabies during life (by intra-vitam techniques) is difficult and dependent on widespread dissemination of virus through the nervous system. It is strongly discouraged for rabies diagnosis in animals as sensitivity varies widely according to the stage of the disease, immunological status, intermittent viral excretion and training of the technical staff.

More information on laboratory techniques in the diagnosis of rabies: