00:01
The rhabdoviridae, viruses.
00:05
Rhabdoviridae
are mid-sized, enveloped viruses with
a helical capsid, and they appear
bullet-shaped.
00:11
You can actually see several of them
on the transmission micrograph
on the right side of the slide.
00:17
They contain a linear, single-stranded,
negative-sense RNA genome,
which means that they must also
carry a RNA-dependent
RNA polymerase, which they do to
help them transcribe their genome.
00:31
The important virus here
is the rabies virus,
and we'll spend some time talking
about what that looks like.
00:39
Rabies virus in the incubation period,
so after exposure to rabies,
can last silently, asymptomatically,
up to a full year or so.
00:51
Now the exposure, as you'll probably remember
from watching movies and
hopefully, the literature,
can come from exposure to a rabid animal.
01:01
nd depending on where the incubation or,
excuse me, where the inoculation occurs,
affects how long the duration of the
asymptomatic incubation is.
01:11
Why is that so?
Because the virus has to travel slowly,
retrograde to the central nervous system.
01:19
So, if one is bitten, for example,
on the first toe,
it has the entire length of the body
to travel to get way up here.
01:27
If one is bitten on the nose, well,
say, "Goodbye, Charlie," because you're gonna
be gone much sooner than a whole 365 days.
01:35
So, if one is lucky and there's been an exposure
peripherally, then it'll be a longer
duration of the incubation period.
01:42
If one is looking for the
virus at that time,
it'll be very difficult.
01:47
One might be able, on biopsy, to see viral
effects by scanning electron microscope
in the muscles surrounding the bite, but the
patient won't have developed antibodies
of a low titer of the virus. It would
have to be a risk-based diagnosis.
02:03
When the disease actually starts,
there is a 2-10 day prodrome,
which includes nonspecific viral symptoms.
02:12
So fever, nausea, vomiting, very
typical, patient has anorexia,
headache, lethargy
Again, you could think of this as,
again, a flu-like illness.
02:22
However, if
they're able to give you the history of
the exposure, the history of the bite,
or whatever the exposure was for the rabies,
then one could actually,
at the site of the exposure,
be able to find a high titer
of rabies virus.
02:39
And one could at least start
to support the patient at that time.
02:44
How successfully would be, well,
it's pretty much unknown.
02:48
There still won't be antibody because
the immune system is still
waking up to the fact
that there has been this exposure to
a foreign substance, to the rabies virus.
02:59
After the prodromal period, there is an
inexorable progression to the neurologic
component of rabies.
03:04
And this is the phase that everybody
recognizes as
classic rabies.
03:08
So the hydrophobia, fear of water,
pharyngeal spasms, hyperactivity,
anxiety, depression,
altered consciousness, paralysis, delirium.
03:18
This is, sort of, the brain
on drugs.
03:21
So, think of every part of the
brain as sped up on
caffeine or speed or something,
and you get a
picture of what these patients are
like, completely out of control.
03:30
This lasts for 2-7 days,
and at this time, you can
finally start to make a very
clear diagnosis
after a clinical suspicion.
03:39
So, biopsing many
highly innervated sites, so any of
the glands, the skin, the eyes.
03:46
The classic spot is the hair follicles
at the base of the neck,
and one can see or one can demonstrate
the rabies virus there.
03:54
One also can find the rabies'
virions through saliva
and antibodies now detectable in the serum
and the central nervous system.
04:03
Ultimately, and despite medical attempts,
the patients progress to coma.
04:07
And here is where they encounter
death through cardiac arrest,
hypoventilation, shock, sometimes
secondary infections.
04:15
And this process may take from,
you know, immediately following
the neurologic complications, or up to 14
days, if there's a secondary infection.
04:25
So, where does rabies come from?
Well, unvaccinated domestic
animals, dogs and cats,
or feral dogs and cats.
04:34
Also, skunks, raccoons, bats are classic.
04:37
The transmission, of course, is the bite
from any of those infected animals,
but so, too, aerosols.
04:44
So think about saliva or body fluids, excreta,
urine, feces, from any of those.
04:51
This accounts for some of the reports from
seeing a bat flying around the bedroom
and then somebody acquiring rabies.
04:59
If the bat was dropping or
exchanging saliva,
it is possible for there to be transmission
of that mechanism.
05:06
So, too, there are some reports of bats
in the ceiling above a bed, above
a hospital bed, in fact,
and somehow, the saliva aerosolized
through the ventilation system and
the patient acquired it.
05:19
So, it's unfortunately very easy to acquire
the rabies virus from excreta,
saliva, urine, etc., from animals.
05:30
Diagnosis.
05:32
It's a neurologic, it's a clinical diagnosis.
05:34
Getting the history of the exposure
if one is lucky, but again, as with the
hospital bed and ceiling encounter,
one may not actually see
the animal or the bat
which might have been the exposure.
05:47
So, with the diagnosis, one can do the biopsies
as we mentioned in the previous slide.
05:53
One could also look pathologically
on those biopsies
for the presence of the Negri
bodies in infected brain.
06:00
And the image on the slide shows you
with several green arrows
these highly eosinophilic collections.
06:06
Those are a collection of capsids,
of virion capsids
from the virus all together, as
they're starting to exit
cytoplasm in the process of
making new virus.
06:18
So,
clinical diagnosis, for sure,
and the treatment.
06:25
Well, I don't have much to say about the
treatment, so let's start with prevention,
, because that's the best way to treat rabies,
to avoid it in the first place.
06:32
So, pets require vaccinations.
06:35
High-risk personnel, perhaps
Animal Control officers
also require vaccination, and there is
a very good vaccine out there.
06:43
However, most often, the prevention is
actually a prophylactic approach
after the exposure has occurred.
06:49
So, if there's a known bite, immediate
attention in a medical personnel,
cleaning the wound deeply with injection
to try and get as much of the
rabies-containing saliva out of the wound.
07:01
And then immunization with
a killed rabies vaccine,
and there will be continued immunizations
at a specific series at
day 3, 7, 14, 21.
07:12
Thankfully, the vaccine series
is much less frequent,
much less painful than it used to be,
but it is still 5 separate shots.
07:21
Also importantly,
because one wants to create
an immune response
at the immediate time of the exposure
without waiting the 2 weeks for immuno-
prophylaxis from the vaccine to develop,
there is passive immunization with
rabies immunoglobulin
And that is injected
if one knows where the bite occurred,
half of the injection is
at and around the site to the bite.
07:45
And the other half is in the
contralateral, deltoid from which the
vaccine was given because
if you gave it at the same site, it's going
to inactivate the vaccine's effect.
07:56
Treatment.
07:56
Unfortunately,
there is no known effective treatment
for symptomatic rabies,
which is almost 100% fatal.
08:03
There are only 29 cases
of confirmed survivors
in the entire world,
and most survived in neurologic sequelae.
08:10
Palliative
therapy can be used to lessen symptoms
including sedatives,
antipsychotics and analgesics.
08:16
There are a few aggressive experimental
treatments that have been attempted,
typically in combination with each other
These include immunotherapy,
antiviral therapy, neuroprotective therapy
such as ketamine and hypothermia,
minocycline and medications
that prevent cerebral vasospasms.
08:34
However, none of these therapies
have been proven to be efficacious.
08:38
So, currently, there's no recommended
use of the protocol.
08:42
It is simply support, support, support,
and hope for the best.
08:46
So, the rabies virus, a very difficult
one because there's
truly no hope for the patients infected.
08:52
The best approach is to
prophylax against it,
and avoid, at all cost, the bite
of a rabid animal.