00:01
Let's start with the enteroviruses.
00:04
Now, the enterovirus family includes
3 major subcategories, which include
enteroviruses, echoviruses,
and coxsackieviruses.
00:14
Related to these 2 are the polio viruses.
00:18
The enteroviruses, as a whole,
are resistant to
acids such as one finds
in the gastrointestinal tract.
00:24
They're also quite resistant to topical
cleaning mechanisms such as detergent.
00:29
Transmission of all of these
is fecal-oral.
00:33
Easy to remember because entero, gut,
is the source of these viruses
in human being.
00:39
Unfortunately, with robust
exposure of vomitus or sometimes
coughing or sneezing,
there can be aerosol transmission as well.
00:49
Typical pathogenesis with the enteroviruses
starts with a primary infection
of the tissue
target for that particular virus.
00:58
Many times, the initial infection
starts in the pharynx,
or the tonsils, the upper airway
in lymphoid tissue,
but then the viruses enter the
gastrointestinal tract.
01:10
Where they spread, then,
depends on the tissue tropism,
and as mentioned, each
virus may have a different specific target.
01:17
It is during that attachment
to a specific tissue
that the cytolytic replication occurs,
meaning the cell is affected by
or entered by the virus,
the virus replicates itself, and when ready
to leave with brand new virions,
it destroys the cell.
01:35
That causes direct tissue damage,
and then depending on the virus, the tissue
damage could be anywhere.
01:42
In the case of polio virus, which
we'll talk about next,
the damage occurs at the level of the
neurons and the neuro-motor junction,
creating central nervous system disease.
01:53
For the other enteroviruses, coxsackie,
echo, enteroviruses,
broad tropism is noted.
01:59
Again, specifically viral subtypes
may attack the brain causing central
nervous system disease,
the lungs, the heart, the pancreas, you name it.
02:09
So, let's look, then, specifically at
poliomyelitis caused by polio virus.
02:16
And rarely, although this is not common,
but rarely, coxsackie A virus.
02:21
Principally, polio virus is the cause of the
disease known as poliomyelitis
and it occurs in 3 different forms.
02:29
The first is what's known as abortive
polio virus.
02:33
This is a very minor illness, which
typically feels like a mild flu-like illness.
02:39
Low grade fevers, some malaise, headaches,
basically the sort of thing which
every one of us acquires
several times a year and sleeps through
for the next 3 days or so.
02:50
In some patients, this disease
might actually be going into a nonparalytic
form of poliomyelitis.
02:59
Of the patients who don't
have the abortive virus,
the remainder 80% will have
this nonparalytic form.
03:06
Here, they start with that same
viral process, viral syndrome,
but it's accompanied by sore throat, sometimes
developing into a stiff neck,
and then they'll actually develop
an aseptic meningitis.
03:19
Not severe in terms of prognosis, although
it's very unpleasant with high fevers,
severe headaches, a stiff neck, everything
which would resemble a meningitis.
03:30
Of the 80% who go into a nonparalytic form,
10% actually may progress
to a paralytic form.
03:38
So it is, sort of, the aseptic
meningitis seen with
nonparalytic, which then progresses
with ongoing destruction of that
lower motor neuron junction
by action of the polio virus itself.
03:50
Those patients develop
the flaccid paralysis, which we're
all familiar with in looking at
historical images, such as the iron lung.
03:59
So, moving on then to the enteroviruses,
the non-polio enteroviruses,
and the first disease category we'll
talk about his herpangina.
04:09
Now, unlike the name, which sounds
a whole awful lot like herpes,
this has nothing to do with oral
herpes or HSV type 1.
04:18
Instead, this is caused primarily
by coxsackie A virus,
sometimes by coxsackie B and
other echoviruses.
04:25
But these viruses have tropism for,
and among other things, the oral mucosa.
04:30
So a patient, typically a young patient,
occasionally an older child
to a young adult,
will first develop fever and sore throat,
along with some neck pain.
04:40
And then after several days of that,
will develop incredibly painful
lesions, ulcerative, or almost
vesicular lesions
on their posterior palate and
over the tonsillar pillars.
04:52
And you can see a picture of this
on the left side of the slide.
04:56
Those lesions are so painful
that most patients
find it impossible to swallow anything,
ncluding their own secretions, and thus
they'll present to health care because
of the pain and dehydration.
05:09
Associated with that particular process
is hand-foot-and-mouth diseases
caused almost exclusively
by coxsackie A virus.
05:18
These patients will have the same
initial fever, sore throat,
plus some nausea and vomiting,
but then they will develop the
same vesicular eruptions,
not just in the back of the mouth
such as herpangina,
but also on the hands and the feet,
typically, the palms and the soles.
05:36
Now, palmer and plantar rash
should be a buzzword in your thinking
because there are very
few infections which can cause that.
05:43
Rocky Mountain spotted fever is one,
secondary syphilis is the second,
and coxsackie A virus causing hand-
foot-and-mouth-diseases
is a common third diseases causing
palmer and plantar lesions.
05:56
These lesions are typically
painful, so children
will not wish to walk.
06:00
They'll be non-ambulatory.
06:02
Adults may experience pruritus,
itching of the lesions,
and it may be that children experience that
also, but are not able to verbalize
the feeling of pruritus.
06:14
Acute hemorrhagic conjunctivitis,
also something that can be seen
with coxsackie A virus.
06:20
And as you see in the picture,
this is a very
hemorrhagic inflammatory process
affecting the conjunctival tissue,
the entire conjunctival tissue,
along with excessive tearing,
mucus discharge,
and even hemorrhaging of the subconjunctiva.
06:35
Again, you can see all these issues
or all these elements
on the picture in front of you.
06:40
This hemorrhagic conjunctivitis
would be like an
adenovirus, pink eye, gone really bad.
06:46
And in fact, adenovirus can do this too,
but it's primarily the coxsackie viruses
that have this severe appearance.
06:54
And then one of my favorites just
because it sounds so neat,
epidemic pleurodynia,
which it has been named Bornholm diseases
and even more -- and you'll love this --
it has been named devil's grip.
07:08
Grippe, G-R-I-P-P-E in historic language,
and it has to do with how severely
painful this is.
07:15
Coxsackie B virus
causing a sudden, sharp
paroxysmal chest pain,
as if the devil has reached out of the
grave and grabbed you by the chest.
07:25
That is how it used to be described,
hence the name.
07:28
However, a Doctor
Bornholm was the one who made
it up bland and boring
with the term epidemic pleurodynia.
07:35
In any event, these patients will have
fever, severe headache,
fatigue, muscle pain, typical viral syndrome,
but with these sudden attacks of
very sharp chest pain,
which, in a way, limit breathing because
they're so painful to take a deep breath.
07:49
Fortunately, the devil's grip is
only 1 week long,
resolves spontaneously, and one can
only provide supportive care.
07:58
Aseptic meningitis.
08:00
Now, we're talking about the enteroviruses,
including coxsackie and echoviruses
that have tropism for the central
nervous system.
08:07
These patients will start off
with, again, fever,
potentially a flat, erythematous,
macular rash,
which is nonspecific, and nausea,
followed then by headache,
neck pain, and the classic presentation
of a meningitis.
08:22
Many of these will occur during the
summer months or the warm
climate months for the country of origin.
08:28
And patients will present and
undergo evaluation for
a bacterial meningitis.
08:34
They will be found to have a certain
number of white blood cells
in the spinal fluid,
but with typically normal protein
and glucose,
suggesting that this is an
aseptic or non-bacterial process.
08:48
And then neonatal disease.
08:50
Infants also can be born to mothers
who are actively infected,
typically with echo viruses
and coxsackie B viruses.
08:57
And if so, they may be delivered
with or soon develop after delivery
signs of neonatal sepsis,
which could be temperature instability,
breathing failure requiring a ventilator,
shock, hypotension requiring cardiac support.
09:15
Basically, depending on the virus and
the organ-specific tropism of the virus,
the babies could present
somewhat differently.
09:22
The most common and most
worrisome presentation
of neonatal sepsis due to any
congenitally or perinatally-acquired
enterovirus
is primary cardiac failure
due to cardiomyopathy or myocarditis
caused, again, by echoviruses.
09:40
So, how do I identify these antiviruses, the
coxsackie echoviruses, coxsackie echos,
the polio viruses?
All these can be identified by looking
at specific body tissues,
including feces, blood serum,
sometimes urine, sometimes respiratory
specimens from a bronchoscopy.
10:01
And in taking a look at these specimens,
one can look or for specific
antibody, in fact,
immunoglobulin M is the most
acutely to be derived,
although unfortunately the least
sensitive in the laboratory.
10:16
You can look for a difference in acute
versus convalescent immunoglobulin
G antibody,
expecting a rise of 4 fold or
higher in the titer,
but far more significantly and sensitively,
we'll now use molecular diagnostics using
a reverse transcriptase PCR
to look at specimens of spinal
fluid or blood
to demonstrate that specific virus.
10:40
The picture you see in front of you is
something we almost never do
because that is a transmission
electron microscope picture
of an echo or actually enterovirus
in the way that it looks, in clustered,
beautifully symmetric form.
10:54
Yeah, we don't do that that often because, A,
it takes forever and B, it's very expensive.
10:59
So, prevention and treatment.
11:01
In very few cases for the enteroviruses,
or polio enterovirus, do we have the
ability to prevent that,
and polio virus is perhaps the best example.
11:11
There's been a long history of a
mostly professional battle between
doctors Salk
and Sabin, who were at the same time almost
in parallel trying to create a vaccine.
11:24
Now, history will suggest that
Dr. Sabin's vaccine
was the winner because his was the
first that was produced
in mass production.
11:31
It was an oral polio vaccine.
11:34
It was a live attenuated, meaning
processed to avoid virulence vaccine,
which was easy to administer and was
administered worldwide.
11:44
Why not Dr. Salk's vaccine?
Because the initial trials
were poorly inactivated.
11:50
There was a problem with the
inactivation process,
and it actually was associated with some
cases of secondary polio.
11:57
He went back to the drawing board and
ultimately created a perfectly successful
safe vaccine, which is in common used today.
12:05
What happened to make the difference
occur between oral polio vaccine --
Sabin's product -- and
injected or inactivated polio virus --
Salk's product?
The challenge is that a live,
attenuated virus
still has some pathogenicity for those
who are immunocompromised,
and so, many patients in a family
who were given the live
oral polio vaccine from Sabin
would shed the polio inactivated
attenuated strain of virus,
and somebody in the family who
was immunocompromised
would acquire that, fecal-oral transfer,
would acquire that, fecal-oral transfer,
So, due to safety reasons, the inactivated
polio virus is what we use,
ertainly in developed countries.
12:50
Although the oral polio
vaccine because it is
easy to administer and easy to deliver
still used in many parts of
third world countries.
12:59
Treatment for any of the enteroviruses
can be attempted, but highly unsuccessfully
with this medication called Pleconaril.
13:07
It's specifically has been tested at
efficacy against enteroviruses,
but it only works to mitigate the
virulence of some of these
some of the time.
13:16
So, tincture of time, lots of support, is the
best way to go in treating any of these.