Antibodies
 
to
 
selected
 
Plasmodium
 
falciparum
 
merozoite
 
antigens
 
are
 
often
 
reported
 
to
 
be
 
associated
 
with
protection
 
from
 
malaria
 
in
 
one
 
epidemiological
 
cohort,
 
but
 
not
 
in
 
another.
 
Here,
 
we
 
sought
 
to
 
understand
this
 
paradox
 
by
 
exploring
 
the
 
hypothesis
 
that
 
a
 
threshold
 
concentration
 
of
 
antibodies
 
is
 
necessary
 
for
protection.
 
We
 
analyzed
 
data
 
from
 
two
 
independent
 
cohorts
 
along
 
the
 
Kenyan
 
coast,
 
one
 
in
 
which
 
anti-
bodies
 
to
 
AMA1,
 
MSP-2
 
and
 
MSP-3
 
were
 
associated
 
with
 
protection
 
from
 
malaria
 
(Chonyi)
 
and
 
another
in
 
which
 
this
 
association
 
was
 
not
 
observed
 
(Junju).
 
We
 
used
 
a
 
malaria
 
reference
 
reagent
 
to
 
standard-
ize
 
antibody
 
measurements
 
across
 
both
 
cohorts,
 
and
 
applied
 
statistical
 
methods
 
to
 
derive
 
the
 
threshold
concentration
 
of
 
antibodies
 
against
 
each
 
antigen
 
that
 
best
 
correlated
 
with
 
a
 
reduced
 
risk
 
of
 
malaria
 
(the
protective
 
threshold),
 
in
 
the
 
Chonyi
 
cohort.
 
We
 
then
 
tested
 
whether
 
antibodies
 
in
 
Junju
 
reached
 
the
 
pro-
tective
 
threshold
 
concentrations
 
observed
 
in
 
the
 
Chonyi
 
cohort.
 
Except
 
for
 
children
 
under
 
3
 
years,
 
the
age-matched
 
proportions
 
of
 
children
 
achieving
 
protective
 
threshold
 
concentrations
 
of
 
antibodies
 
against
AMA1
 
and
 
MSP-2
 
were
 
signiﬁcantly
 
lower
 
in
 
Junju
 
compared
 
to
 
Chonyi
 
(Fishers
 
exact
 
test,
 
P
 
<
 
0.01).
 
For
MSP-3,
 
this
 
difference
 
was
 
signiﬁcant
 
only
 
among
 
4–5
 
year
 
olds.
 
We
 
conclude
 
that
 
although
 
antibodies
are
 
commonly
 
detected
 
in
 
malaria
 
endemic
 
populations,
 
they
 
may
 
be
 
present
 
in
 
concentrations
 
that
 
are
insufﬁcient
 
for
 
protection.
 
Our
 
results
 
have
 
implications
 
for
 
the
 
analysis
 
and
 
interpretation
 
of
 
similar
data
 
from
 
immuno-epidemiological
 
studies.