UOA01-02: Malaria Treatment in Pregnancy
Submitting InstitutionUniversity of Oxford
Unit of AssessmentClinical Medicine
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Paediatrics and Reproductive Medicine
Summary of the impact
Research by the University of Oxford's Shoklo Malaria Research Unit
(SMRU), Mae Sot (Thailand), has had a significant impact on the health
outcomes of pregnant women and infants in malaria affected areas, with
findings leading to major changes in World Health Organization
recommendations for the prevention and treatment of malaria in pregnancy.
Its studies have established the optimum treatment regimes (using
artemisinin-based drugs) and have shown that early detection and treatment
of malaria, including asymptomatic infection, during pregnancy prevents
maternal mortality, morbidity, and improves the outcome of pregnancy.
Contracting Malaria during pregnancy is estimated to cause as many as
10,000 maternal deaths and up to 8% of all infant deaths each year1.
Despite these statistics, malaria in pregnancy has been a relatively
neglected problem, with less than 5% of pregnant women having access to
effective interventions. This situation has been due to both the absence
of data measuring the impact of malaria during pregnancy, and the lack of
information regarding the safety of malarial drugs for both the mother and
fetus. To address these problems, Professor François Nosten and his
research team at the University of Oxford's Shoklo Malaria Research Unit
(SMRU) set out to study the epidemiology, prevention and treatment of
malaria during pregnancy, in an area of multidrug resistance in South East
Asia. Over 26 years SMRU has carried out the largest prospective cohort
study of malaria in pregnancy, with detailed assessment and follow up of
over 50,000 pregnancies between 1986 and 2012. It also undertook a number
of randomised controlled treatment trials (including pharmacokinetic
studies) on malaria in pregnancy.
In the largest published series of epidemiological studies on malaria in
the first trimester (17,613 women), SMRU found that the risk of
miscarriage increases in women with malaria, whether symptomatic or not.
They also found that there was no significant effect on miscarriage or
congenital abnormality rates as a result of the antimalarial drugs they
used, and that P. vivax malaria, which is often considered a
benign infection, is also associated with fetal loss in the first
trimester2. To further understand the effects of malaria on the
fetus, SMRU also conducted detailed ultrasonography studies using 3D
imaging technology. The studies showed that the fetal head diameter is
reduced after a single (often asymptomatic) infection3, as well
as the placenta volume; this provided further evidence of the deleterious
effect of malaria (both falciparum and vivax) on early fetal growth.
Treatment Trials and Pharmacokinetic Studies:
Early detection of parasitaemia and prompt treatment with a safe and
effective therapy, are paramount to the reduction of maternal mortality
and the adverse effects of malaria in pregnancy. Due to the
ineffectiveness of generally recommended drugs (quinine,
sulfadoxine-pyrimethamine, and chloroquine) against multidrug resistant P.falciparum
parasites, SMRU set out to study the safety and efficacy of various
antimalarials in pregnancy4. Of all treatment tested, 7 days of
quinine/clindamycin and 3 days of Malarone/artesunate provided the best
outcome, with more than 90% efficiency. These trials also provided
evidence that the artemisinins were safe in pregnancy5. SMRUs
final pharmacokinetic trial, published in 2008, showed that the standard
six-dose (3 days) artemether-lumefantrine regimen was well tolerated and
safe in pregnant Karen women with uncomplicated falciparum malaria. This
trial also showed that the efficacy was lower than the 90% recommended by
the WHO because of low concentrations of lumefantrine6.
References to the research
World Health Organisation's statistics on malaria during pregnancy.
2. McGready, R. et al. Adverse effects of falciparum and vivax
malaria and the safety of antimalarial treatment in early pregnancy: a
population-based study. Lancet Infect Dis 12
Research from SMRU showing there is no significant effect on
miscarriage or congenital abnormality rates as a result of
3. Rijken, M. J. et al. Ultrasound evidence of early fetal growth
restriction after maternal malaria infection. PLoS One 7,
e31411 (2012). doi: 10.1371/journal.pone.0031411.
Study showing the fetal head diameter is reduced after a single
4. McGready, R. & Nosten, F. The Thai-Burmese border: drug studies of
Plasmodium falciparum in pregnancy. Ann Trop Med Parasitol 93
Suppl 1, S19-23 (1999).
Paper reporting on the safety and efficacy of various antimalarials
5. McGready, R. et al. Artemisinin antimalarials in pregnancy: a
prospective treatment study of 539 episodes of multidrug-resistant
Plasmodium falciparum. Clin. Infect. Dis. 33, 2009-2016
Study showing ACTs are safe in pregnancy.
6. McGready, R. et al. A randomised controlled trial of
artemether-lumefantrine versus artesunate for uncomplicated plasmodium
falciparum treatment in pregnancy. PLoS Med. 5, e253
(2008). doi: 10.1371/journal.pmed.0050253.
SMRUs final pharmacokinetic trial showing the standard six-doze
antimalarial treatment is safe in pregnant women with malaria.
This research was funded by the Wellcome Trust.
Details of the impact
In 2007 there were an estimated 54.7 million pregnancies in areas with
stable P. falciparum malaria, and a further 70.5 million in areas
with low malaria transmission. With the increasing use of artemisinin
combination treatments for malaria, the survival rates of those in
affected areas have increased. As pregnant women are often excluded from
drug treatment trials, however, (particularly trials of newer
antimalarials) they have continued to receive ineffective treatment7.
The prospective research conduced by the SMRU has had a significant
impact on the health outcomes of pregnant women and infants in malaria
affected areas, with findings leading to major changes in world health
policy relating to malaria in pregnancy.
Results from SMRU's epidemiological and pharmacokinetic studies, which
provided evidence for the first time of the deleterious effect of malaria
on early fetal growth, have led to a significant paradigm shift in
clinical and world health policy. Although it was once considered
acceptable for pregnant women with asymptomatic malaria to remain
untreated, SMRU's research has shown that malaria must be prevented and
treated as early as possible during pregnancy. This has led to changes in
the World Health Organization malaria treatment guidelines in pregnancy8,
and the Green Top Guidelines on Prevention9 and Treatment10
of malaria in pregnancy.
SMRU recently provided much of the evidence for the Annual World Health
Organization Meeting on treatment and prevention of malaria in pregnancy
in the Asia Pacific Region in 201111. Now collaborating with
other investigators to promote treatment and pharmacokinetic studies in
pregnancy in Africa12 and Papua New Guinea13, SMRU
is also a partner in the Malaria in Pregnancy Consortium. The research
team has produced 96 articles, book chapters and abstracts on the topic of
Early detection and treatment of malaria in pregnancy has had clear
benefits to Karen woman and the local community on the border of Thailand.
This has been highlighted by the large reduction in malaria related
maternal mortality (from 1,000 deaths per 100,000 in 1985 to zero in 2005)14,
an increased birth weight in local infants (from 2.7 to 3 kg), and the low
prevalence of placental malaria related lesions. Due to SMRU's research,
early detection and treatment is increasingly being recognised as an
effective strategy to reduce the morbidity and mortality caused by malaria
in areas of low transmission. On the Thai-Myanmar border the beneficiary
population extends to the refugee and the migrant workers communities —
circa 300,000 people. The deleterious effects of malaria (P.falciparum
but also P.vivax) are also increasingly being recognised.
The change in pregnancy surveillance has also had a dramatic impact on
mortality rates related to non-malaria febrile illness, including adverse
fetal outcomes in those with rickettsial infection. This has also
significantly improved health outcomes for mothers and infants in the
Sources to corroborate the impact
- White, N. J., McGready, R. M. & Nosten, F. H. New medicines for
tropical diseases in pregnancy: catch-22. PLoS Med. 5,
e133 (2008). doi: 10.1371/journal.pmed.0050133.
Paper reporting ineffective ACT treatment in pregnant women.
- World Malaria Report [online]. Geneva: World Health Organization, 2009
Available at: http://whqlibdoc.who.int/publications/2009/9789241563901_eng.pdf
WHO Malaria treatment guidelines for pregnant women.
- Royal College of Obstetricians and Gynaecologists The prevention of
malaria in pregnancy [online]. (54A RG-tg, ed.):,2010 Available at: http://www.rcog.org.uk/files/rcog-
corp/GTG54aPreventionMalariaPregnancy0410.pdf (Accessed 2012)
The RCOG Green-top Guidelines on the prevention of malaria in
- Royal College of Obstetricians and Gynaecologists.The diagnosis and
treatment of malaria in pregnancy [online]. (54B RG-tg, ed) 2010 :
Available at: http://www.rcog.org.uk/files/rcog-
The RCOG Green-top Guidelines on the treatment of malaria in
- Rijken, M. J. et al. Malaria in pregnancy in the Asia-Pacific
region. Lancet Infect Dis 12, 75-88 (2012). doi:
SMRUs report on the treatment and prevention of malaria in the
Asia-Pacific region, presented at the Annual WHO Meeting 2012.
- Piola, P. et al. Efficacy and safety of
artemether-lumefantrine compared with quinine in pregnant women with
uncomplicated Plasmodium falciparum malaria: an open-label, randomised,
non-inferiority trial. Lancet Infect Dis 10, 762-769
(2010). doi: 10.1016/S1473-3099(10)70202-4.
Collaboration study into the efficacy and safety of antimalarials
in pregnant women in Africa.
- Poespoprodjo, J. R. et al. Adverse pregnancy outcomes in an
area where multidrug-resistant plasmodium vivax and Plasmodium falciparum
infections are endemic. Clin. Infect. Dis. 46, 1374-1381
(2008). doi: 10.1086/586743.
Collaboration study into the efficacy and safety of antimalarials
in pregnant women in Papua New Guinea.
- McGready, R, M. et al. Effect of early detection and
treatment on malaria related maternal mortality on the north-western
border of Thailand 1986-2010. PLoS One. 7, e40244 (2012).
Report showing the large reduction in malaria related maternal
mortality on the north-western border of Thailand between 1985 to
- McGready, R. et al. Arthropod borne disease: the leading
cause of fever in pregnancy on the Thai-Burmese border. PLoS Negl Trop
Dis 4, e888 (2010). doi: 10.1371/journal.pntd.0000888.
Report showing improved outcomes from mothers and infants on the