Background:

Malaria transmission has declined substantially in the 21st
century but pregnant women in areas of sustained transmission still require protection to prevent the adverse pregnancy
and birth outcomes associated with malaria in pregnancy
(MiP). A recent “Call to Action”
has been issued to address the continuing low
coverage of intermittent preventative
treatment for malaria during pregnancy (IPTp).
This call has, however, been questioned by
some, in part due to concerns about resistance to
sulphadoxine
-
pyrimethamine (SP)
, the
only drug currently recommended for IPTp.

Methods and Findings:

Using an existing mathematical model of MiPwe combined estimates of the changing
endemicity of malaria across Africa with
maps of
SP
resistance mutations
and current
coverage of antenatal access and IPTp
-
SP
across Africa. Using est
imates of the relationship
between these mutations and the parasitological
efficacy of SP during pregnancy
,
we
estimate the varying impact of IPTp
-
SP across Africa
and the
incremental value of enhancing
IPTp
-
SP uptake to match current
antenatal clinic (ANC
)
coverage.
The risks
of MiP
and
malaria
-
attributable low birthweight
(
m
LBW)
in unprotected
pregnan
cies
(i.e. those not using insecti
ci
de treated nets (ITNs))
leading
to live births
fell
by
37%
(33%
-
41%
95% credible interval (crI
)
)
and 31% (27%
-
34
%
95%
crI)
respectively
from
2000 to 2015
across
endemic
areas
in
sub
-
Saharan Africa
. However
,
these gains are fragile
,
and coverage is far from optimal
. I
n 201
5
,
9.5
(8.3
-
10.4 05% crI)
million (m)
of
30.6m
pregnancies in
these
areas
would
still
have been infected
with P. falciparum
without
intervention
, leading to
750,000
(
39
0
,000
-
1
.
1
m
95% crI
)
)
malaria
-
attributable
LBW
deliveries.
6.6
(
5.6
-
7.3 95% crI)
m
of
these
9.5m
(69.3%)
pregnancies
at risk of
infection
(
and
53.4% [
16.3
m
/30.6m] of all
pregnancies)
occurred in settings with near
-
perfect SP
curative efficacy (>99%)
based on
the most recent estimates of
resistance
. 4
4
%
of these
pregnancies
(
23
% of all
pregnan
cies
) are not receiving
any
IPTp
-
SP
despite
making >= 3
ANC
visits,
representing
160
,000
[
94
,000
-
236
,000
95% crI]
preventable
LBW deliveries
.
Only
4
%
61
(
1
.
4
m
) occurred in settings with >
10
% prevalence of the sextuple haplotype
associated with
compromise
d
SP effectiveness. 4
2
%
of all pregnancies
occurred in settings
where
the
quintuple dhfr/dhps haplotype
had become established
but where in
-
vivo efficacy data
suggests SP
maintains
the majority of its effectiveness in clearing infection
s
.
Not accounting for protection from the use of ITNs during pregnancy, expanding IPTp
-
S
P to
all women with >=3 ANC visits in Africa could prevent an additional
215
,000
[1
28
,000
-
315
,000 95% crI
]
LBW deliveries. In 26 countries with sufficient recent data to estimate ITN
impact
(population
-
based ITN usage data that can be stratified by gravidi
ty)
,
we estimate
that
, due primarily
to
low
ITN
use in primigravidae
,
only 16.5% of the potential LBWs
prevented by scaling up
IPTp
-
SP
would in fact have already have been prevented through
ITN use.
Our analysis also highlights the difficulties associated w
ith estimating the relationship
between
the effectiveness of interventions against
parasitological endpoints
such as
placental infection at delivery
and health outcomes
including
birthweight
, the latter of
which
is also
determined by a wide range of non
-
re
lated factors. We also do not capture
other aspects of malaria burden such as clinical malaria, maternal and neo
-
natal anaemia
and miscarriage
, all of which increase the overall importance of effective preventative
strategies but will have their own relati
onship with transmission intensity, parity and SP
resistance
.

Conclusions:
Despite recent declines in malaria transmission in Africa, the burden of MiP in the absence
of adequate prevention remain
s
substantial. E
ven accounting for SP resistance, extending
IPTp
-
SP to all women attending ANC
, as well as LLIN distribution targeted towards first time
mothers,
would have a
sizeable
impact upon
maternal and
infant health in almost all
malaria endemic settings in sub
-
Saharan Africa.