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A hematogenously disseminated Orientia tsutsugamsushi-infected murine model of scrub typhus.
[scrub typhus]
Orientia
tsutsugamushi
,
the
etiologic
agent
of
scrub
typhus
,
is
a
mite-borne
rickettsia
transmitted
by
the
parasitic
larval
stage
of
trombiculid
mites
.
Approximately
one
-
third
of
the
world
's
population
is
at
risk
of
infection
with
Orientia
tsutsugamushi
,
emphasizing
its
importance
in
global
health
.
In
order
to
study
scrub
typhus
,
Orientia
tsutsugamushi
Karp
strain
has
been
used
extensively
in
mouse
studies
with
various
inoculation
strategies
and
little
success
in
inducing
disease
progression
similar
to
that
of
human
scrub
typhus
.
The
objective
of
this
project
was
to
develop
a
disease
model
with
pathology
and
target
cells
similar
to
those
of
severe
human
scrub
typhus
.
This
study
reports
an
intravenous
infection
model
of
scrub
typhus
in
C
5
7
BL
/
6
mice
.
This
mouse
strain
was
susceptible
to
intravenous
challenge
,
and
lethal
infection
occurred
after
intravenous
inoculation
of
1
.
25
×
10
(
6
)
focus
(
FFU
)
forming
units
.
Signs
of
illness
in
lethally
infected
mice
appeared
on
day
6
with
death
occurring
∼
6
days
later
.
Immunohistochemical
staining
for
Orientia
antigens
demonstrated
extensive
endothelial
infection
,
most
notably
in
the
lungs
and
brain
.
Histopathological
analysis
revealed
cerebral
perivascular
,
lymphohistiocytic
infiltrates
,
focal
hemorrhages
,
meningoencephalitis
,
and
interstitial
pneumonia
.
Disseminated
infection
of
endothelial
cells
with
Orientia
in
C
5
7
BL
/
6
mice
resulted
in
pathology
resembling
that
of
human
scrub
typhus
.
The
use
of
this
model
will
allow
detailed
characterization
of
the
mechanisms
of
immunity
to
and
pathogenesis
of
O
.
tsutsugamushi
infection
.
Diseases
Validation
Diseases presenting
"lethal infection"
symptom
scrub typhus
typhoid
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