Discussion:
Rabies is a zoonotic disease and potentially vaccine-preventable. Despite the existence of safe and effective anti-rabies vaccines, cost and awareness were the major constraints in Asia and Africa.(8)
In the Arabian Peninsula, RABV is enzootic with human cases of RABV have been reported previously in Qatar.(9) The vaccination status of the host, proximity of the bite to the brain, the inoculum size, and the virulence of RABV strain are the major determinants of the incubation period which is varies from days to years.(5) Most rabies infection is transmitted by exposure to saliva from an animal bite, mainly carnivores or bats. Clinically, RABV infection presents in 2 distinct major forms, around 65% will develop the furious type and the remaining paralytic rabies. Other forms of presentation include; multi-organ involvement, renal failure, acute respiratory distress syndrome, pericarditis, and myocarditis with complete heart block.(5) In addition to, Agitation, confusion, signs of autonomic dysfunction, and hydrophobia (pathognomonic) and aerophobia were all reported. Phobic spasms in response to tactile, auditory, visual, or olfactory stimuli pose high mortalities within days without intensive ventilatory support. The pathophysiology for the characteristic aggressive behavior in the encephalitic form of rabies remains unknown.(10) Our patient is a young male who recently arrived in Qatar with unidentified animal bite 3 months before arrival with no history of post exposure vaccination or rabies immune globulin administration. He presented with typical symptoms of rabies encephalitis and hydrophobia. These make the diagnosis of rabies encephalitis high in the list of our differential diagnoses, but we were opting to cover for viral and bacterial encephalitis and consider other possibilities like toxic or metabolic encephalopathy pending the work-up.
There are no routine sensitive tests for antemortem diagnosis, despite advances made in understanding the virus behaviors. Detection of virus antigen in brain tissue remains the gold-standard diagnostic technique with almost 100 % sensitivity. Hemi-nested polymerase chain reaction (RT-hnPCR) showed high sensitivity and specificity irrespective of the time to clinical symptoms or sample collection. The downside of RT-hnPCR is not routinely available.(4) The negative serum and CSF neutralizing antibodies against the virus up to the tenth day after symptoms limit the use of the test for assessing antibody response after vaccination rather than the diagnostic role which explains the negativity of the tests in our patient as the sample taken two days into the symptoms.(11) In our case, the negativity of the PCR tests in CSF and nape of skin biopsy did not preclude the diagnosis of rabies since the clinical suspicion was high and can be elucidated by absent of viremia, intermittent virus shedding, time of the sample collection and transportation or storage of the samples.(4) There are no specific findings for rabies in imaging studies compared with other viral encephalitides. However, MRI findings of frontotemporal hyperintense signals may be seen.(12) .There are no documented medical treatment for clinical rabies so far. The aim is to prevent the development of rabies by wound care and postexposure prophylaxis with hyperimmune rabies serum and active immunization. These interventions reduce the mortality risk from 37-60 % to almost zero following a bite from a rabid animal.(13). Many factors influence the adoption of an aggressive management protocol for confirmed or suspected rabies infection. Besides, awaiting or unavailability of the rabies tests in the early stage of the illness should initiate the aggressive treatment without delay.(10) Inducing coma and treating with antiviral drugs to allow the native immune response to mature is the basis of the debated Milwaukee Protocol.,(15) Looking at the young age of the patient and the benefits of the doubts, we decided to adopt initially the aggressive approach. The patient received a rabies vaccine and in the context of encephalitic symptoms, Ceftriaxone and acyclovir were added to cover for possibilities of bacterial and viral encephalitis respectively. Furthermore, Ribavirin added, and Ketamine was used to induce the coma as recommended in the Milwaukee Protocol. Despite these measures, the patient continues to deteriorate and eventually died. Infection control precautions were practiced by all health care workers caring for the patient.