Review

M a la riain pregnancy:prioritiesfor research

Brian G reen wood,
PedroAlo nso,Feiko O ter K u ile,Jen n yH ill,R ich a rdW Steketee

Resea rch on the im portant topic of m alaria in p re gn ancyhas bee n relativelyneglected. TheLancet InfectDis 2007; 7:
seven technicalreview sin this special issue on malaria in pregnancyprovidean overviewof 169–74
current knowledgeon k e y aspects of malaria in pregnancy and highlight the gaps where Departmentof
m ore research is needed. In this paper, we prioritise research needs, focusing on areas of Infectiousand Tro pica l
Diseases, Lon d on
research lik e ly to lead to improvem entsin maternal and child health in malaria endemic S ch oo lof H y g ie n eand
areas in the near or mid term. We have selected the follo w in gas the highest prioritiesfor Tro p ic a lMedicine,
research: identification of new safe and effective drugs to treat malaria in pregnancy; L o n d o n ,U K
identification of new drugs to replace sulfadoxine-pyrimetham inefor intermittent (Prof B Greenwood M D );
C e n trefor
preventive treatment in pregnancy; identification of optimum combinationsof control International H e alth ,
measures in different epidem iologicalsettings; and determination of optim um w ays of Hospital C lin ic ,
scaling-up the use of insecticide-treatedmosquito nets and intermittent preventive U n iv e rs ityof
Barcelona, Barcelona,
treatment.
Spain
(P A lo n soM D ); C en trode
Investig açãoe m S aúd eda
Introducti demonstrationthat and practice has
on antibody responses can block this process been too slow.
Although the problem of malaria in pregnancy and lead to Furthermore, the
was first partial protection from the adverse effects of background
chronicled in the medical literature malaria in knowledge on
approximately pregnancy, the possibility of developing a which current
70 years ago,1 it has been a neglected area vaccine that policy
of research. prevents cytoadherence is now being recommendations
Early studies defined the epidemiology of explored.4 It has for the
malaria in also been shown that inflammatory responses management of
pregnancy in areas with moderate or high to malaria malaria in
levels of parasites and their products in the placenta, pregnancy are
transmission and studied methods of sometimes based is limited.7
treatment and resulting in accumulation of mononuclear The advances in
prevention using chemoprophylaxis. Studies cells in the the control of
done in the intervillous blood space, are an important malaria in
past 15 years have focused on prevention of component of pregnancy that have
malaria in the pathology of placental malaria. However, been made in
pregnancy by administration of how these recent years are
sulfadoxine- inflammatoryprocesses interfere with placental now being
pyrimethamine intermittently during pregnancy function jeopardised by the
and on is not well understood and many questions spread of
use of insecticide-treated mosquito nets. This about the antimalarial and
research pathogenesis and management of malaria in insecticide
has led to recommendations by WHO on the pregnancy resistance and
control of remain there has been
malaria in pregnancy in areas with moderate unanswered.5,6 lack of progress in
to high the development of
levels of Backgroundand rationalefor the new drugs for the
m alariain pregnancyresearch treatment and
transmission.2 reviews
Research in the past decade has The rate at which evidence on the efficacy of prevention of
insecticide- treated nets and intermittent malaria, and a lack
improved our preventive treatment in pregnancy (IPTp) in
understanding of the biological basis for preventing malaria in pregnancy was of progress in the
susceptibilityto gathered, and the rate at which the development of
malaria in pregnancy including the crucial part encouraging findings of this research have alternative
been translatedinto policy
playedby insecticides that
adherence of Plasmodium falciparum-infected red could be used for
blood insecticide-treated
cells to the glycan chondroitin sulphate A, nets. Lack of
resulting in coordination
the accumulation of parasitised red blood cells between research
in the groups, the private
placental blood space.3 Following the sector, donors, and
policymakers responsible for implementation has need for M a n h iça ,M in isteriode
more research on many aspects of malaria in Saúde, M oza m b iq u (P e
also hindered the development of improved
A lo n so;) C h ildand
methods for managing malaria in pregnancy. pregnancy, ReproductiveH ealth
For these reasons, a group of interested extending across a wide range of disciplines that Group, Live rp o oSch l o ol
scientists met on several occasions in 2005 and include of Tro pica lMedicine,
basic biology and immunology, epidemiology, Liverp oo l,U K (FO ter K u ile
2006 to consider ways in which research on
MD, J H ill MSc); and
malaria in pregnancy, and the translation of economics, Programfor
important research findings into practice, could and public Appropriate
be accelerated. This special issue of The Lancet health. Tec h no lo g yin H ealth,
In this Review, however, priority has been Batiment Avant
Infectious Diseases is one result of the
Centre,
collaboration established during these given to Ferney-Voltaire,France
meetings. Major gaps in knowledge are research that is likely to lead to improvem entsin (R S te kete eM D )
identified in the seven preceding reviews. This maternal C orresp ond ence to:
paper highlights some of the key areas for and child health in malaria endemic areas in the ProfessorBrian
Greenwood, Departm entof
further research identified by the authors of the near or
In fectiou sand Tro p ic a l
preceding papers and shows how these could be mid term. For each of the areas covered by the Diseases, Lond onS ch oolof
drawn together to form a rational research preceding H y g ienea n d Tro p ic a l
strategy. papers, up to five topics have been selected M e d icin e , K ep pStreet,
el
London
as high W C 1 E7 HT, U K .
Re se arch research priorities. Some prioritisation of Te l + 44 (0) 207 299
4707; fax + 44 (0) 207
priorities research issues 299 4720;
The authors of this and the other malaria in was done during meetings of the wider group of brian.greenw ood@lshtm .
ac.uk
pregnancy scientists
papers in this issue recognise that there is a who have contributed to the reviews in this
special issue.

http://infection
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Review

We then took these issues and prioritised them for the fetus and the infant after delivery.
under five main areas through a series of one- Investigating the effect of malaria during the
to-one meetings and electronic exchanges. The first trimester of pregnancy is important in
w ays in which the broader group of topics could determining how aggressively researchers should
be prioritised further to constitute an overall pursue the developmentof preventivestrategies
research strategy and how this research
programme might be implemented most
effectivelywere then reviewed.
See Review page
105
M ala riain p re g n a n cya s a m a jo r
c au s eof m ortalityand
morbidity
In recent years, the burden of malaria in
pregnancy in sub-Saharan Africa has been
estimated with some degree of confidence as
See Revie w described in the paper by Meghna Desai and
page 93 colleagues.8 However, some questions about
the burden of mortality and morbidity
attributable
to malaria in pregnancy remain unresolved.
These unresolvedissues are describedbelow.

The im p o rtanc eof m alariaas a causeof

m ate rnalm ortalityin areasof m edium
or high m alariaendemicity
Recent autopsy studies done in Mozambique
suggest that malaria may be a more frequent,
direct cause of maternal mortality than has
previously been appreciated and that it is both
under and over-diagnosed as a cause of serious
illness or death during pregnancy. Careful clinical
studies of serious illnesses in pregnant women
resident in areas of varying malaria endemicity,
accompanied if possible by post-mortem studies,
are needed.

T h e c lin ic a l im p ortan ce of m ala ria in

pregnancy outside the high-transm ission
areas of Africa
There are few data on the effect of P falciparum
infection on pregnancy in areas outside Africa,
such as parts of Asia and Latin America where
malaria transmission is generally much less
intense than in Africa, single infections in
pregnancy are common, and women have little
immunity to malaria. In many of these areas,
both P falciparum and Plasmodium vivax coexist
and little is known about the effect of P vivax or
combined infections on pregnancy. Further
study of the impact of P vivax infection on
pregnancy is needed to help define health
priorities in areas where this infection is
prevalent. These studies could also provide
valuable information on the pathogenesis of
malaria in pregnancy(see below).

The im p o rtanc eof m alariain th e fi rs t

trimester of pregnancy
In most malaria endemic areas, few pregnant
women attend an antenatal clinic before the
second trimester of pregnancy. Consequently,
little is known about the importance of
malaria infections in the first trimester of
pregnancy and their long-term consequences
that reach women munity immunological and haematological techniques
early in their There are many outstanding questions should allow m any of these uncertainties to be
pregnancy. Such about the resolved.
studies will not pathogenesis of malaria in pregnancy, as set
be easy to do out in the Studyof the path ogen esisof fetal growth
and will review by Stephen Rogerson and colleagues.9 restrictionand pretermbirth
probably require Research in The mechanisms by which malaria parasites
longitudinal this area is likely to provide important cause fetal growth restriction and preterm
studies of women information about birth are not well understood. Cytoadherenc e
in the reproductive the biology of malaria parasites in general is likely to be a key factor in the case of P
age- group to as well as falciparum infections but how cytoadherence
detect early elucidating the pathogenesis of malaria in impairs placental function is not known. Since
pregnancies. pregnancy. infection with P vivax, which does not cytoadhere,
Areas of research likely to contribute to also leads to low birthweight, other factors,
P improved perhaps hormonal or nutritional, must be involved.
a management of malaria in pregnancy in the Because HIV also causes preterm births, studies
t short to on the role of malaria in the pathogenesis of
h medium term include the preterm births should include both HIV-infected
following: and non- infected women. Resolving the
o complicated and interacting mechanisms
g S tudyof the pathogenesisof anaem ia involved in the pathogenesis of malaria-
e in pregnantw om eninfectedw ith P induced low birthweight will not be easy.
n falciparumor P vivax However, new techniques are being developed
e Severe anaemia is probably the main for the study of malaria- infected placentas
s mechanism by which malaria causes mortality obtained at delivery such as perfusion of the
in pregnant women, yet its pathogenesis has placenta or placental lobule, microdissection of
i not been studied in detail. The relative the syncytiotrophoblast , and use of cell lines.
s importance of haemolysis, bone marrow Nevertheless,study of placental function in vivo
suppression (perhaps cytokine induced), is difficult and animal models might be helpful in
a and sequestration of parasites in this area of research.
n the placenta as causes of severe anaemia in
d pregnancy has not been defined. How malaria Studyof the im pactof effectivecontrol
interacts with other important causes of m easureson the developm entof im m unity
anaemia in pregnancy, such as HIV and to m a lariain pregnancyWomen infected with
i nutritional deficiencies, is also unknown. malaria during their first pregnancydevelop
m Careful clinical studies using modern immunity to parasites that sequester in the

170 http://infection
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 Review

placenta. Thus, there is a danger that effective vaccination of D

control of malaria in first pregnancies through women in the child-bearing age before i
IPTp, insecticide- treatednets or indoor residual pregnancy, a
insecticide spraying will impair this process, including adolescents,is likely to be a more g
increasing the risk of malaria acquired effective and n
during subsequent pregnancies. Whether or safer option than vaccinationduring pregnancy. o
not this is the case needs to be established by Research s
clinical and epidemiological studies and by will be needed on the acceptabilityof this i
studies of cellular and humoral immune approach and s
responses in women living under different on the optimum way of achieving this goal, In some
epidemiological situations protected from perhaps by epidemiological
malaria in various ways. Study of the impact of giving the malaria vaccine withother adolescent situations—eg,
effective control of malaria in pregnancy on vaccines areas with low
vertical transmission of HIV is also required. such as the human papillomavirus vaccine. levels of
transmission—
Vaccination C a sem anagem entand case detection
Vaccines provide a potentially important pharm acovigilance Finding alternativesto and treatment
w ay of the failing drugs currently being used for the may be the most
preventing malaria in pregnancy. Any highly treatment and prevention of malaria in
pregnancy is probably the most urgent task effective approach
effective, facing the research community, as pointed out to the
pre-erythrocyticvaccine that induces protection by François Nosten and colleagues.10 It is management
and is generallyagreed that new drugs or drug
combinations that do not alreadyhave a clear of malaria in
not strain specific should protect against safety record in pregnant women should be pregnancy.
malaria in tested first in pregnant women with proven However,
pregnancy. Thus, once it has been established malaria before they are tried for IPTp because peripheral blood
the risk–benefit ratio is likely to be more
that a pre- favourable in the former situation. There microscopy is a
erythrocytic vaccine can induce a are several priority areas for research in this relatively insensitive
substantial and area: method of
sustained level of protection in non-pregnant detecting
adults or malaria infection of
children, a trial to determine its ability to protect the placenta and
against new diagnostic
malaria in pregnancy would be justified. tests
Vaccination are needed that
with the product of the var gene responsible for are sensitive
binding enough to detect
of P falciparum to chondroitin sulphate A is a infection
potential of the placenta,
method for preventing malaria-induceddamage and yet simple and
to the cheap enough to
placenta and consequent low birthweight.It is be
likely, but u
not proved, that prevention of sequestration s
would also e
reduce the incidence of maternal anaemia. d
Research to
develop pregnancy specific, anti-cytoadherence i
vaccines n
is, therefore, a priority. Vaccination during
pregnancyis t
unlikely to be the most effective way of h
deploying a e
malaria in pregnancyvaccine because it may be
important c
to protect women from malaria during the first l
trimester i
of pregnancy before they present at an n
antenatal clinic. i
Additionally, there are concerns over the c
safety of .
vaccination during pregnancy. Thus,
Find ingne w d rug sfo r the treatm entof for the
malariain pregnancy treatment and prevention of malaria in
In nearly all malaria endemic areas, chloroquine pregnancy.
can no longer be used for the treatment of P Pharmacokinetic studies are also an
falciparum infections in pregnancy, although it can essential, early
still be used to treat P vivax infections in many requirement in the evaluation of new
places. The efficacy of sulfadoxine- antimalarials being
pyrimethamine is also falling. Thus, trials of considered for this purpose. Such studies are
potential alternatives to these two drugs are likely to
needed urgently. The drugs that have the highest require the collection of detailed
priority for testing w ill vary from area to area measurements in a
depending upon the local pattern of resistance. small number of women together with smaller
numbers
D evelopm ent of a standardm ethodfor the of samples from a larger number of treated
evalu ationof new treatm entsfor m alariain women with
pregnancy modelling of the findings (population
Evaluation of new treatments in pharmacokinetics).
asymptomatic,parasitaemic pregnant women
requires a different approach from that used
to measure efficacy in symptomatic, highly
parasitaemic children and may give different
results. Assessment of safety requires
demonstration that the drug does not produce
adverse effects in the mother or the fetus.
Determining the latter requires that the
pregnancy should be followed to its conclusion,
the newborn baby examined for congenital
abnormalities and the baby followeduntil 6 weeks
of age and, wheneverpossible, to 1 year of age.
Thus, evaluation of new treatments for malaria
in pregnancy is more complex, demanding, and
expensive than treatment trials in children or non-
pregnant adults. The development of standard
w ays of conductingsuch trials is a priority.

P harm acokineti
cs
There are few data on the
pharmacokinetics of
antimalarial drugs in pregnancy and several
antimalarials,
including sulfadoxine-pyrimethamine, have been
used
extensively in pregnancy in the absence of the
information
needed to determine the correct dose.
Pharmacokinetic
studies in pregnant women are urgently
required for
some of the antimalarials currently in use See Re v ie wpa ge 118

http://infection
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Review

Important areas of research that have net plus IPT, or that the frequency of dosing with
attracted little attention from the research existing and future drugs used for IPT can be
community are the potential for adverse reduced when an insecticide-treated net is
pharmacokinetic interactions between used. Similarly, it needs to be established
antimalarials and antiretroviralsand the effect of whether IPT adds to the protection provided by
malaria on the pharmacokinetics of indoor residual spraying.
antiretrovirals.

P harm acovigila IPTp

nce Sulfadoxine-pyrimethamineis currently the only
Conventionaltrials of new treatments are likely to drug
involve recognised for IPTp and, although it may remain
only a few hundred women and are too small to effective
detect for IPT, even when its efficacy in treating
rare but important adverse events. Thus, symptomatic
the malaria has waned, alternatives are needed
establishment of pharmacovigilance systems urgently. It is
able to not known whether IPT requires a long-acting drug
detect rare adverse events following treatment and
with new therefore trials of effective short and long-acting
antimalarial drugs is a priority. Because drugs
See Review page artemisinin- are needed to resolve this issue. Whether IPTp
136 based combination therapies, now being with
used sulfadoxine-pyrimethamineis of benefit and safe in
increasingly widely, can cause fetal loss in HIV-
monkeys as infected women who are receiving co-
well as rodents when exposure takes place trimoxazole
early in prophylaxis for opportunistic infections needs
pregnancy, establishing effective to be
pharmacovigilance resolved.
systems at selected sites where these drugs
See Review page are being Com binations of
126
used has become urgent. Ways in which this interventions
might be There is an urgent need to determine the best
See Revie w page
145 done are discussed by Stephen Ward and possible
colleagues.1 1 combination of drug-based and vector control
strategies
P re v en tio n o f m alaria in needed in different epidemiological
See Revie w page pregnancy settings.
156
Detecting malaria infections in pregnancy can be
difficult Moderate to high transmission
in highly endemic areas since most areas
infections are It is uncertain whether IPTp with
asymptomatic. Thus, in such communities, sulfadoxine- pyrimethamine provides added
prevention benefit to insecticide- treated nets in all
of malaria in pregnancy is a major public-health circumstances. It is possible that in some
priority. situations, use of a long-lasting insecticidal net
Two tools are currently being used to do this— and case detection may be as effective as an
IPTp and insecticide-treated
insecticide-treated nets—as discussed by Clara
Menendez
and colleagues.12 The research priorities
related to
increasing use of these interventions are
discussed
subsequently by Jane Crawley and colleagues.13
Additional
research issues include the
following:

N e w d rug s for
Low transmissio n areas much greater than in Africa. In some areas summarised in the review by Eve Worrall and
including those outside outside Africa, where vectors bite predominantl
y colleagues,14
Africa Remarkably during the day or early evening, repellents may which identifies gaps requiring further
little is known have a role in preventing malaria in research.
about how pregnancy and this needs to be investigated.
malaria in An analysi s of the overall economci burden
pregnancy can be Safety of insecticides in of m a la ria in pregnancy
prevented most pregnancy An analysis of the overall economic burden of
effectively in Asia Research to develop alternative insecticides malaria in pregnancy that considers both direct
and Latin that could be used for treatment of nets or for and indirect effects— eg, the long-term
America. Studies indoor residual spraying in areas where there is consequences of low birthweight on child
comparing case resistance to insecticides currently used for development—woul d be helpful in defining the
management alone public health is underway. It will be necessary to importance of malaria in pregnancy as a
against preventive demonstrate as far as possible that exposure of global public- health priority. More information on
approaches plus pregnant women to such insecticides is not the burden of malaria in low transmission areas
case management harmful to them or to their fetuses. (see above) will be needed to guide this review.
are needed. More Information on the safety in pregnancy of the
information is insecticides currently being used for treating Cost-effectivenes s of insecticide-treate
d
needed on the nets or for indoor residual spraying, mainly nets and IPT in pregnancy
value of pyrethroids and DDT, is limited and may also Previous studies have demonstrated that,
insecticide- need further evaluation. overall, both insecticide-treated nets and IPT
treated nets in are highly cost-effective interventions when
Asia and Latin Econom used in pregnancy. However, more refined
America where the ics studies are needed to establish the cost-
diversity and The economic aspects of malaria in pregnancy effectiveness of insecticide-treated nets, indoor
complexity of the have been residual spraying, and IPT in different
main vectors are neglected.The limited information available epidemiological situations and when delivered
is through alternative systems. For

172 http://infection
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2007
 Review

Panel:T h e to p p rioritiesfo r rese archon

m a lariain pregnancy. Ca te go ry1: stu dy Ca tego ry2: study results C a teg ory3: study results
could help
re su ltscou ldcha nge could substantially im prove ach ievehigh coverage w ith w h atw e
1 Fin d ingsa fe an d e ff e ctivene w d ru g sor d ru g w hatw e d o w h atw e do shou ldbe doing

com binationsfor th e treatm entof m alariain

pregnancy Va ccinefor m alaria
in preg nan cy
2 Fin d in gsa fe a nd eff e ctivea lte rn a tivetos
sulfadoxine-
pyrim etham ine for IPTp O ptim a l S cale-up
D ru g s D ru g sfor
com binations of
3 D e fi n ingth e o p tim u mcom b ina tionof control for p reventio
in existing
treatm e n
measures nt
d iff erent recom m endation
M a la riain first transm ission s
in diff eren tepidem iological situations trimester settings
4 Find in gop tim u mw a ysfo r sca lin g-upu se of
insecticide-
treatednets and D iagn ostic s,burden,
IPTp pathophysiology,
immunology, economics

example, it is not known at what level of can be integrated more effectively than in the past with
malaria transmission use of insecticide-treated reproductivehealth and other programmes directed at women of
nets or IPT become cost-effective interventions childbearing age. For example, schedules for IPTp may need to be
nor what level of resistance to sulfadoxine- adapted to meet the new WHO four-visit recommendations for
pyrimethamine would negate the cost- antenatal care. Could the skills of traditional birth attendants be
effectiveness of IPT. used to facilitate malaria control? Collaboration with adolescent
health pro- grammes may provide access to women during (or
Im plem entatio
n and health policy before) their first pregnancy and a possible route for the distribution
research of preventive measures such as insecticide- treated nets or
New tools for the control of malaria in vaccines. Ways need to be found of improving collaboration
pregnancy have between malaria control and HIV treatment programmes.
become available during the past decade but
coverage with
these interventions is still unacceptably low. Jane
Crawley
and colleagues13 point out that research on
defining the
obstacles to progress has been neglected and
they identify
a number of areas where research is needed.
These topics
are listed
below.

Identification of optim um delivery strategie

s
for scaling-up the use of insecticide-treate
d
nets and IP T
Research is needed to identify the most effective
and most cost-effective ways of delivering
insecticide-treated nets and IPT in different
epidemiological and social circumstances in a
sustainable way. Universal coverage with
insecticide-treated nets is the ultimate goal for
high risk areas but, in the meantime, some
more restricted strategies may be required—
eg, distribution of free or subsidised nets at
antenatal and immunisation clinics. Alternative
approaches to delivery need to be explored.

Integratio
n of m alaria control w ith
reproductive healthprogrammes
An important area of operational research that
needs to be addressed is how malaria control
 C c ru c ia to
l m aternal,fe tal, an d n ew bornhealth.
a C ate go ry2 : the resultsof stu diesin th is g ro up cou ld sub stan tiallyimprove existingtools and
t controlstrategies.
e Ex a m p le sin cludethe de v e lo p m e ntof ne w safe a nd eff e ctived ru gsfor treatm entand
g
for IPTp an d the
o
r develo pm e ntof strategie sfor the preve ntionof m a lariain p reg nany. c C ateg ory3: th e resu lts
y of stu diesin this
ca tegorycould help to a chie v ehig he rle v e lso f cov e ra g ew ith e xistin g,proven intervention s.
4 Re searchfindings
: co u ld b e a v a ila b lein th e n e a r te rm a n d ra p id lyin fl u e n c e c o n tro l strategies. C a te go ry4:
s rese archin this category
t in cludes a broad ra nge of studies in w hich im portant inform ationca n be obtaine d in
u
associatio nw ith other
d
y in ve stig atio ns,fo r e xa m pleacq uiringkno w ledg eo n the im m un olog y o f m ala riain pre gna n cydu ring
treatmentor
r vaccine trials or com bining stu dies of new diagnostics w ith
e interventionstudies.
s
u
l A ccess, aff ordabilit
y, and
t
s
acceptability
More research is needed on the accessibility,
w affordability,
i
l
and acceptability of current and new
l interventions.
i Physical access to services does not guarantee
n
f their use
o because of factors such as quality of care or
r
m waiting time.
Assessment of the acceptability of a new
w
h
intervention,
a both by pregnant women and by the health-care
t workers
w asked to deliver it, must be an integral
e component of the
d
evaluation of any new method for the
o prevention of
malaria in pregnancy and requires the
n
o participation of
w social
a
scientists.
n
d
T h e top researchp rioritiesand a
i
strategyfor futureresearch
Four areas have been selected from among
n
the topics considered above as being the
t most urgent research priorities (panel).
h Identification of new drugs and new drug
e combinations that can be used safely and
effectively in pregnancy heads the list. We
f have also categorised future research needs
u into four main areas (figure). New studies will
t vary in their feasibility, ease of conduct and
u timeframe. For example, the timeframe for the
r development of a vaccine that is safe and
e effective in pregnancy is likely to be long, but
success could greatly change the way in which
malaria in pregnancy is managed. The
F igure: A co nc ep tu alfram e w o rkan d strate gy for a second category of research focuses on crucial
program meof resea rchon m ala riain pregnancy studies that are required to give early results
T he fig ure depicts four categ orie s of research .Cate gory 1 : and which need to be coordinated effectively to
stu die sin this ca te g o ryincludethose w h ichcould achieve this goal. Their feasibility is higher than
cha n ge ho w m a la ria in pre gna n cyis m a na g e d.T he y in clud e studies in the first category and they are likely
de v e lo p m e nt
of a safe and effectivevaccineand to give early, practical benefits. The third category
d e m on strationthat prev en tionof m alariain th e first trim e ste ris of

http://infection
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Review

research findings into policy and practice

Searchstrateg yand selectioncriteria
and the implementation of effective new
Th ispa p eris b a sedo n a re vie wo f the preceding ways of containing malaria in pregnancy as
pap ersin this issu eand of relevantsupporting speedily and cost effectivelyas possible.
articles. C onfl icts of
interest
We declare that we have no conflicts of
interest.
research—eg, studies on the pathogenesis of
Acknow ledgm e
malaria in pregnancy, informs the future but
nts
may not immediately change or modify existing We are grateful to the Bill and Melinda Gates
interventions. Finally, studies in category four Foundation for the
tend to be less about research and more financial support that has facilitated this review
process. The
about acquiring the knowledge needed to categorisation of research priorities presented in this paper
make good decisions on service delivery and to represents
increase coverage. the views of the authors. We are grateful to the other
Each of these sets of research questions members of the
malaria in pregnancy working group who have
needs to be approached systematically by contributedto the
groups that have the necessary technical priorities listed in this paper and who have provided helpful
knowledge to address them; this may require a comments
new and larger set of scientific and programmatic on the
manuscript.
relationships than currently exist. Study
Referenc
of new treatments will require the creation es
of clinical trials networks with experience of 1 Wickaramsuriya GA. Clinical features of malaria in
treatment of malaria in pregnancy, and pregnancy.
Malaria and ankylostomiasisin pregnant women. London:
groups with experience in large-scale field Oxford
studies and demographic surveillance will be University Press, 1937.
needed for epidemiological studies and 2 WHO/AFRO. A strategic frameworkfor malaria prevention
and controlduring pregnancyin the African region.
prevention trials. With skill, it should be possible Brazzaville: World Health OrganizationRegional Office for
to integrate into these major work programmes Africa, 2004.
studies of cross-cutting issues such as those on 3 Fried M, Duffy PE. Adherence of Plasmodium falciparum to
chondroitin sulfate A in the human placenta. Science
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