Treating Malaria in Pregnancy: Searching for an Answer

The present WHO malaria treatment guidelines state that, “The antimalarials considered safe in the first trimester of pregnancy are quinine, chloroquine, proguanil, pyrimethamine and sulfadoxine–pyrimethamine. Of these, quinine remains the most effective and can be used in all trimesters of pregnancy including the first trimester.”  The guidelines go on to say that, “There is increasing experience with artemisinin derivatives in the second and third trimesters (over 1000 documented pregnancies). There have been no adverse effects on the mother or fetus.”  Where problems arise is choosing a safe partner drug for ACTs, as WHO has come out against monotherapy artemisinin treatment. The unfortunate balance is between known safe drugs, for which resistance has grown, or drugs that have not been sufficiently tested.  WHO concludes that, “Despite these many uncertainties, effective treatment must not be delayed in pregnant women.”

dscn9999a.JPGThe thorny issue of treating malaria in pregnancy has been addressed in recent journal articles.  In The Lancet Nosten et al. Emphasize the importance of prompt and appropriate treatment because of the severe impact malaria has on the mother, the fetus and eventually the newborn. Dellicour et al. in Malaria Journal conclude that with the ‘limited data available’ artemisinins are unlikely to cause fetal loss or abnormality when used late in pregnancy.

Ward et al. in The Lancet believe that adequate ‘information is not available’ on toxicological liabilities of artemisinins on the mother and fetus.  At the same time Valley et al. in Malaria Journal provide a whole table of potential drugs that can be used in pregnancy for IPTp and discuss the safety of these.

All authors agree that there are inadequate studies of large enough size to come to definitive solutions, and all are concerned about the ethnics of testing drugs during pregnancy.  Is the answer to this dilemma treatment with pharmacovigilance, which would be challenging in resource poor endemic areas? Is the solution clinical trials?  Pharmacovigilance faces another challenge. When health workers are told on one hand not to give artemisinins to pregnant women and on the other to report any adverse reactions to artemisinins the result is no data due to fear of repercussions if supervisors found that artemisinins were given to a pregnant woman

Can infected women wait? The reality is that in most endemic countries national malaria case management policy simply states that health workers should prescribe the currently accepted national malaria treatment for pregnant women, though they do address the need for such drugs as quinine during the first trimester.

Health workers in the field need answers and guidance, and international bodies like WHO need to step forward quickly with a more definitive course of action to find those answers.

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