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.