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Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis.
[congenital toxoplasmosis]
Over
1
billion
people
globally
are
estimated
to
be
infected
with
Toxoplasma
gondii
with
severe
or
unknown
consequences
and
no
safe
and
effective
therapies
are
available
against
congenital
or
persistent
chronic
infection
.
We
propose
that
atovaquone
and
diclazuril
synergistically
protect
against
fetal
-
maternal
toxoplasmosis
.
Programmed
pregnant
mice
were
treated
with
atovaquone
and
diclazuril
monotherapy
,
or
combined
(
atovaquone
+
diclazuril
)
therapy
and
infected
with
tachyzoites
(
0
,
300
,
600
)
and
the
course
of
infection
was
studied
.
Infected
dams
with
low
dose
(
300
)
developed
moderate
toxoplasmosis
complications
and
treatments
were
similarly
effective
with
minor
differences
between
monotherapies
.
In
contrast
,
major
differences
were
observed
amongst
varied
treatments
during
high
-dose
(
600
)
infection
and
severe
related-
toxoplasmosis
complications
as
follows
.
Dams
developed
hydrothorax
,
ascities
and
excess
weight
gain
.
Combined
therapy
(
P
<
0
.
01
)
and
to
a
lesser
extent
diclazuril
monotherapy
(
P
<
0
.
05
)
protected
dams
from
excess
weight
,
hydrothorax
,
and
ascities
.
Infected
dams
exhibited
splenomegaly
,
hepatomegaly
and
severe
hepatitis
.
Combined
therapy
synergistically
normalized
pathology
(
P
<
0
.
001
)
and
to
a
lesser
degree
monotherapy
(
diclazuril
P
<
0
.
01
,
and
atovaquone
P
<
0
.
05
)
protected
dams
from
hepatitis
and
splemomegaly
.
Additionally
,
behavioral
response
to
pain
stimuli
and
fetal
weight
and
fetal
numbers
were
significantly
preserved
in
treated
dams
.
This
is
the
first
report
describing
combined
atovaquone
and
diclazuril
therapy
(
a
)
to
be
safe
in
pregnancy
,
(
b
)
to
exert
novel
synergistic
effects
,
and
(
c
)
to
protect
dams
and
their
nested
fetuses
against
adverse
effects
of
severe
toxoplasmosis
.
Diseases
Validation
Diseases presenting
"splenomegaly"
symptom
alpha-thalassemia
congenital toxoplasmosis
familial mediterranean fever
monosomy 21
papillon-lefèvre syndrome
primary effusion lymphoma
proteus syndrome
scrub typhus
severe combined immunodeficiency
typhoid
waldenström macroglobulinemia
This symptom has already been validated