Editorial Commentary: Intermittent Preventive Treatment in Pregnancy With Sulfadoxine–Pyrimethamine: The Controversy Continues
0
Julie Gutman Division of Parasitic Diseases and Malaria
, Malaria Branch,
Centers for Disease Control and Prevention
,
Atlanta, Georgia
EDITORIAL COMMENTARY
-
Each year, approximately 32 million
pregnancies occur in malaria-endemic
areas of Africa [1]. Malaria in pregnancy
(MiP) is a serious condition that
contributes to both maternal and infant
morbidity and mortality. It is estimated
that up to 200 000 infant deaths occur
annually as a result of MiP (http://www.
who.int/features/2003/04b/en/). In order
to decrease the risk of Plasmodium
falciparum infection in pregnancy and
subsequent morbidity and mortality, the
World Health Organization (WHO)
recommends intermittent preventive
treatment in pregnancy (IPTp) with at least
2 doses of sulfadoxine-pyrimethamine
(SP) 1 month apart after quickening. As
resistance of Plasmodium falciparum,
the most important malaria species in
MiP, to SP has increased in the past 2
decades with a concomitant decrease in
the efficacy of SP for treatment of
children <5 years of age, the continued
benefit of providing IPTp-SP has been
questioned [2]. IPTp-SP continues to
provide benefit to mothers and infants
in areas where the rate of treatment
failure in children is up to 39% [3];
however, where treatment failure rates
are higher, and when coverage with
insecticide-treated bednets is high,
IPTpSP appears to provide less benefit [4, 5].
More worrisome are data from Muheza,
Tanzania, suggesting that IPTp-SP may
be harmful, exacerbating placental
malaria and contributing to fetal anemia
[6, 7]. If this finding is replicated in
other areas, it will have significant
implications, as it would suggest that the
practice of providing IPTp-SP to women
in areas with high levels of SP resistance
should be discontinued immediately,
rather than continuing this practice until
an alternate drug for prophylaxis in
pregnancy is found.
In this issue of Clinical Infectious
Diseases, Rogawski et al provide reassuring
data from a large retrospective delivery
cross-sectional study in Malawi that
IPTp-SP is not associated with fetal
anemia or cord hemoglobin
concentration [8]. There was no evidence that this
lack of association changed over time as
SP resistance increased. Furthermore,
their data suggest that IPTp-SP
continues to provide some beneficial effect, as
evidenced by the finding that malaria
parasitemia at delivery had the largest
effect on fetal anemia among
primigravid women who did not take SP and no
significant effect among multigravid
women whether or not they took SP.
This is consistent with what has been
reported previously; IPTp-SP has been
shown to be beneficial in primigravid
and secundigravid women, but it
remains unclear whether there is a
benefit to women of higher gravidity [9].
The fact that IPTp-SP may still confer
some benefit to primigravid women in
Malawi is an important finding,
especially in light of the fact that Malawi has
high levels of molecular resistance to SP,
with nearly 100% saturation of quintuple
mutants, although mutations such as
dhps 581 or dhfr 164, which are
associated with higher level SP resistance, are
still rare [10]. This suggests that
although it is necessary to explore
alternative therapies to IPTp-SP, it need not be
abandoned yet.
It is important to note that other
studies that have examined the issue of
fetal anemia following maternal SP use
have also found that IPTp-SP decreases,
not increases, the prevalence of fetal
anemia [5, 11]. The reason for the
discrepancy between these studies and the
study conducted in Muheza may have to
do with the extremely high level of
resistance found in the Muheza area, with
14-day treatment failure rates in children
of 68% (no recent studies in children
have been done in Malawi to compare
with this) or with the relatively higher
proportion of dhps 581 mutations in
Muheza than can be found in other
study sites. The data from Muheza
suggesting that SP is responsible for the
fetal anemia are convincing: cord sulfa
concentration was found to inversely
correlate with cord hemoglobin levels.
However, of the 880 women studied,
cord samples for sulfa analysis were
available from 847 and IPTp-SP history
was available from 826, but only 685 are
used in the analysis of fetal hemoglobin.
It is unclear how this subset was
identified for analysis, and whether this could
have affected the results.
Another issue to consider in future
studies examining the effectiveness of
IPTp-SP is which women should be
included. Initial studies of IPTp-SP focused
on primigravid and secundigravid
women, as they have the least
pregnancyspecific malaria immunity, and so are at
the greatest risk [12]. As
insecticidetreated bednet coverage and other
malaria interventions are scaled up and
transmission declines, it is likely that the
effects of MiP will increasingly be seen in
women of higher gravidity. However, if
we really want to evaluate whether
IPTpSP continues to reduce the burden of
MiP, we should choose the women most
likely to benef (...truncated)