Abstract
BackgroundArtemisinin combination therapy (ACT) is recommended for the treatment of multidrug resistant malaria in the second and third trimesters of pregnancy, but the experience with ACTs is limited. We review the exposure of pregnant women to the combination dihydroartemisinin-piperaquine over a 6 year period.MethodsFrom April 2004–June 2009, a prospective hospital-based surveillance screened all pregnant women for malaria and documented maternal and neonatal outcomes.ResultsData were available on 6519 pregnant women admitted to hospital; 332 (5.1%) women presented in the first trimester, 324 (5.0%) in the second, 5843 (89.6%) in the third, and in 20 women the trimester was undocumented. Peripheral parasitaemia was confirmed in 1682 women, of whom 106 (6.3%) had severe malaria. Of the 1217 women admitted with malaria in the second and third trimesters without an impending adverse outcome, those treated with DHP were more likely to be discharged with an ongoing pregnancy compared to those treated with a non-ACT regimen (Odds Ratio OR = 2.48 [1.26–4.86]); p = 0.006. However in the first trimester 63% (5/8) of women treated with oral DHP miscarried compared to 2.6% (1/38) of those receiving oral quinine; p<0.001. Of the 847 women admitted for delivery those reporting a history of malaria during their pregnancy who had been treated with quinine-based regimens rather than DHP had a higher risk of malaria at delivery (adjusted OR = 1.56 (95%CI 0.97–2.5), p = 0.068) and perinatal mortality (adjusted OR = 3.17 [95%CI: 1.17–8.60]; p = 0.023).ConclusionsIn the second and third trimesters of pregnancy, a three day course of DHP simplified antimalarial treatment and had significant benefits over quinine-based regimens in reducing recurrent malaria and poor fetal outcome. These data provide reassuring evidence for the rational design of prospective randomized clinical trials and pharmacokinetic studies.
Highlights
Malaria in pregnancy (MiP) is an major global health problem associated with an increased risk of severe adverse events contributing to both maternal and infant mortality [1,2]
Early diagnosis and prompt treatment with effective antimalarial drugs are important interventions for reducing these adverse outcomes [3,4], this strategy is under threat from the emergence and spread of multidrug resistant parasites [5]
The World Health Organisation advocates three alternatives for the treatment of malaria in the second and third trimesters of pregnancy: an Artemisinin combination therapy (ACT) known to be effective in the country/region, a 7 day course of artesunate plus clindamycin, or a 7 days course of quinine plus clindamycin
Summary
Malaria in pregnancy (MiP) is an major global health problem associated with an increased risk of severe adverse events contributing to both maternal and infant mortality [1,2]. Recent evidence from clinical trials has highlighted the adverse impact of even a single episode of malaria in the first trimester of pregnancy and its association with miscarriage [7]. These observations have lead some authorities to call for a review of the safety and efficacy of artemisinin based treatment regimens with regard to optimizing malaria the management in early as well as late pregnancy. Artemisinin combination therapy (ACT) is recommended for the treatment of multidrug resistant malaria in the second and third trimesters of pregnancy, but the experience with ACTs is limited. We review the exposure of pregnant women to the combination dihydroartemisinin-piperaquine over a 6 year period
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