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Hello, my name is
Katie Flanagan.
I'm an infectious
diseases specialist and
vaccinologist based
in Australia.
I'm going to talk about
rotavirus vaccines today.
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Rotavirus are wheel-like particles
of the Reoviridae family.
They are large viruses,
approximately 100
nanometers in diameter.
They're non-enveloped
double-stranded RNA.
The double-stranded
RNA encodes for
six structural proteins and
six non-structural proteins.
There are three serotypes that
cause disease in
humans: A, B, and C.
But most of the human
cases are serotype A.
It's a very highly
contagious infection which
is transmitted
fecal-orally, generally,
but also via fomites.
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Rotavirus causes a huge
global burden of disease with
over 125 million cases
occurring annually,
and nearly all children
would have been infected by
rotavirus by the
age of five years.
Rotavirus causes
approximately 40% of
the diarrheal
hospitalizations and
around 200,000 people will die
every year from infection.
If you look at the map,
you can see that the burden of
the disease is particularly in
Sub-Saharan Africa,
India, and Indonesia.
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Rotavirus causes diarrhea
via a number of mechanisms.
Rotavirus invades
the small intestinal
gut mucosa by
entering into the mature
enterocytes either
at the mid or the upper
part of the villi,
as you can see on the diagram
on the right-hand side.
The diarrhea then
will be caused by
malabsorption, in particular,
where the villi have become
stunted and shortened and
they're unable to
absorb that well.
They also get destroyed.
There are a lot of
pro-inflammatory cytokines such as
nitric oxide and other
pro-inflammatory mediators.
There's an inhibition of
the uptake of fluid
and electrolytes.
There's also a secretory component
leading to osmotic diarrhea.
The villi become ischemic,
and the other mechanism
of diarrhea is by
increased motility of
the intestines due to
the activation of the
enteric nervous system.
You can see all of those factors
occurring in the diagram.
One of the viral
proteins, NSP 4,
acts directly as an
enterotoxin as well.
