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Hemoglobinopathic erythrocytes affect the intraerythrocytic multiplication of Plasmodium falciparum in vitro.
[alpha-thalassemia]
The
mechanisms
by
which
α-thalassemia
and
sickle
cell
traits
confer
protection
from
severe
Plasmodium
falciparum
malaria
are
not
yet
fully
elucidated
.
We
hypothesized
that
hemoglobinopathic
erythrocytes
reduce
the
intraerythrocytic
multiplication
of
P
.
falciparum
,
potentially
delaying
the
development
of
life-threatening
parasite
densities
until
parasite
clearing
immunity
is
achieved
.
We
developed
a
novel
in
vitro
assay
to
quantify
the
number
of
merozoites
released
from
an
individual
schizont
,
termed
the
"
intraerythrocytic
multiplication
factor
"
(
IMF
)
.
P
.
falciparum
(
3
D
7
line
)
schizonts
produce
variable
numbers
of
merozoites
in
all
erythrocyte
types
tested
,
with
median
IMFs
of
27
,
27
,
29
,
23
,
and
23
in
control
,
HbAS
,
HbSS
,
and
α-
and
β-thalassemia
trait
erythrocytes
,
respectively
.
IMF
correlated
strongly
(
r
(
2
)
=
0
.
97
;
P
<
.
001
)
with
mean
corpuscular
hemoglobin
concentration
,
and
varied
significantly
with
mean
corpuscular
volume
and
hemoglobin
content
.
Reduction
of
IMFs
in
thalassemia
trait
erythrocytes
was
confirmed
using
clinical
parasite
isolates
with
different
IMFs
.
Mathematical
modeling
of
the
effect
of
IMF
on
malaria
progression
indicates
that
the
lower
IMF
in
thalassemia
trait
erythrocytes
limits
parasite
density
and
anemia
severity
over
the
first
2
weeks
of
parasite
replication
.
P
.
falciparum
IMF
,
a
parasite
heritable
virulence
trait
,
correlates
with
erythrocyte
indices
and
is
reduced
in
thalassemia
trait
erythrocytes
.
Parasite
IMF
should
be
examined
in
other
low
-indices
erythrocytes
.
Diseases
Validation
Diseases presenting
"anemia severity"
symptom
alpha-thalassemia
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