Laboratory diagnosis of human rabies: recent advances

Abstract

Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly through the bite of a rabid animal, is responsible for an estimated 61,000 human deaths worldwide. The true disease burden and public health impact due to rabies remain underestimated due to lack of sensitive laboratory diagnostic methods. Rapid diagnosis of rabies can help initiate prompt infection control and public health measures, obviate the need for unnecessary treatment/medical tests, and assist in timely administration of pre- or postexposure prophylactic vaccination to family members and medical staff. Antemortem diagnosis of human rabies provides an impetus for clinicians to attempt experimental therapeutic approaches in some patients, especially after the reported survival of a few cases of human rabies. Traditional methods for antemortem and postmortem rabies diagnosis have several limitations. Recent advances in technology have led to the improvement or development of several diagnostic assays which include methods for rabies viral antigen and antibody detection and assays for viral nucleic acid detection and identification of specific biomarkers. These assays which complement traditional methods have the potential to revolutionize rabies diagnosis in future.

Figure 1

Fluorescent antibody technique (FAT) on human brain smear positive for rabies.

Figure 2

Diagnosis of rabies by the Rapid Rabies Enzyme Immunodiagnosis (RREID) technique. Note the dark brown colouration obtained with rabies positive brains in comparison to negative brains which appear colourless.

Figure 3

Virus isolation in cell culture: street virus infected Neuro-2a (a) and HEK 293 (b) stained with fluorescent antibody technique (FAT).

Figure 4

The Direct Rapid Immunohistochemical Test (dRIT) technique done on a human brain positive for rabies. Note the presence of brownish red particles in a neuron spreading along dendrites and axon.