Artemisinin Antimalarials in Pregnancy: A Prospective Treatment Study of 539 Episodes of Multidrug‐ResistantPlasmodium falciparum

Abstract

The emergence and spread of multidrug-resistant Plasmodium falciparum compromises the treatment of malaria, especially during pregnancy, where the choice of antimalarials is already limited. Artesunate (n=528) or artemether (n=11) was used to treat 539 episodes of acute P. falciparum malaria in 461 pregnant women, including 44 first-trimester episodes. Most patients (310 [57.5%]) received re-treatments after earlier treatment with quinine or mefloquine. By use of survival analysis, the cumulative artemisinin failure rate for primary infections was 6.6% (95% confidence interval, 1.0-12.3), compared with the re-treatment failure rate of 21.7% (95% confidence interval, 15.4-28.0; P=.004). The artemisinins were well tolerated with no evidence of adverse effects. Birth outcomes did not differ significantly to community rates for abortion, stillbirth, congenital abnormality, and mean gestation at delivery. These results are reassuring, but further information about the safety of these valuable antimalarials in pregnancy is needed.

Efficacy and safety of dihydroartemisinin-piperaquine

“…There have been no prospective assessments of DHA-PIP in pregnant women. There are concerns over the safety of artemisinin derivatives in the first trimester of pregnancy, although increasing confidence of safety in the second and third trimesters (McGready et al, 2001;WHO, 2003). Preclinical testing with piperaquine has raised no specific concerns for pregnancy so DHA-PIP may be a potential antimalarial for pregnant women, but clearly prospective studies of pharmacokinetics, efficacy, and safety are needed.…”

The Antimalaria Agent Artemisinin Exerts Antiangiogenic Effects in Mouse Embryonic Stem Cell-Derived Embryoid Bodies

“…Because artemisinin treatment resulted in a strong reduction of vascular growth in the embryonic tissue of ES cell-derived embryoid bodies, the application of the drug at least at high doses used in the present study should be avoided in pregnant women. Although artemisinin at low doses used for antimalaria treatment has been recently demonstrated to be well tolerated in pregnant women, and birth outcomes did not differ significantly from community rates for abortion, stillbirth, congenital abnormality, and mean gestation at delivery, further information about the safety of these valuable antimalarials in pregnancy was requested (McGready et al, 2001). This is all the more important because in mice, hamsters, guinea pigs, and rabbits, both dihydroartemisinin and artesunate showed contragestational effects (Xu et al, 1996).…”

Therapy of Falciparum Malaria in Sub-Saharan Africa: from Molecule to Policy

“…Pharmacovigilance systems are not well established in China and Southeast Asia, but, despite this, it is important to note that no spontaneous reports of congenital abnormalities have been published. Furthermore, published data on nearly 1,000 pregnancies (nearly 100 from the first trimester) have shown no evidence of treatment-related adverse pregnancy outcomes (26,85). While these results are encouraging, the numbers are too small to establish the safety of these compounds when used to treat malaria in pregnant women, and pharmacovigilance systems are now being established to increase the database.…”