Test for rabies in transplantation

DFA test with FITC anti-rabies Ab
in a transverse frozen section of
brain stem from a rabies infected donkey (200X mag)

Rabies is a RNA virus typically present in the saliva of infected mammals.   The rabies virus can be detected by testing saliva, serum, skin biopsy of hair follicles at the nape of the neck, neck biopsy, cerebral spinal fluid and brain biopsy.   Since rabies is present in nervous tissue,  the brain is an ideal location to test for the rabies antigen.  A set of minimum standards for rabies diagnosis in the US was established in 1999.  The first step was to create a standard protocol using the direct fluorescent antibody (DFA) assay.  A FITC-anti-rabies monoclonal globulin is used.  The incorporation of two reagents prepared from different pools of monoclonal antibodies greatly reduces the chance of a false negative due to non-recognition of a specific variant.    Strict adherence of all labs to this established protocol is vital and decreases false positive and false negative results.  All laboratories performing the DFA test for rabies are asked to participate in national rabies virus proficiency.  Once every 6 years each laboratory should send a representative to the National Laboratory Training Network course to obtain details about rabies testing and discuss common problems.  The field has been working hard to expand off this gold standard.  A through review of the emerging technologies in rabies detection was published by Fooks et al.   In order to decrease the time to detection researchers created a direct Rapid Immunohistochemical Test (dRIT) which can be read in one hour and uses a streptavidin-peroxidase reaction to visualize which negates the need for a fluorescence microscope.   These methods confirm rabies post-mortem and research is focusing on development of ante-mortem testing using molecular methods.  Nucleic acid testing using SYBR Green I Real time PCR has been able to diagnose patients ante mortem for rabies using saliva or hair follicle samples with a sensitivity around 63%.   A new reverse-transciption heminested (RT-hnPCR) method obtained a high specificity of greater than or equal to 98%.  The authors suggest a skin biopsy should be taken and tested from cases of encephalitis of unknown origin.

What appears to be key is obtaining a complete patient history including possible exposures to an infected animal through a bite, scratch or contact.  Where the patient lives and any traveling to foreign countries.  In addition recognizing the flu like symptoms a patient would present with including fever, malaise, headache, cerebral dysfunction, delirium, hallucinations or insomnia.   According to the CDC, the acute phase ends after 2 to 10 days and once a person exhibits signs of the disease, survival is rare with only 10 documented cases of recovery.  Guidelines for the prevention on rabies has been outlined by the CDC.    

This brings up the recent case of a man who died of rabies after receiving a kidney transplant 16 months ago from an infected donor. All the recipients in this case are being tested for rabies and as a precaution are receiving rabies vaccination.   The CDC stated at the time of death the donor had signs of encephalitis, but was not screened for rabies and no viable test is currently done given the timeframe of transplant.  A rapid test ante-mortem seems possible given the great strides made in this area and could migrate is rare complication.