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Re: Malaria in pregnancy

Sir,

We were encouraged to see the review of malaria in pregnancy by Whitty et al. in the BJOG,1 given the huge burden of this disease and the lack of therapeutic and prophylactic options. As stated by the authors, the risk of significant morbidity and mortality from withholding a drug for treatment of this condition usually outweighs the risk of toxicity. However, we would like to share the following comments.

We question the notion that pregnant women with malaria in Africa are asymptomatic: in fact, there are no large and detailed longitudinal studies to support this hypothesis, and most papers on treatment trials report the presence of symptoms in infected women, even in areas of high transmission. It is unlikely that a pregnant woman infected with Plasmodium falciparum will remain completely asymptomatic and more likely that she will have mild symptoms that will not be reported. Maternal mortality attributed to malaria is high in Africa,2 a fact that is hard to reconcile with absence of symptoms. This is important as many pregnant women with malaria may be left untreated because there is a view that asymptomatic malaria does not need to be treated. Furthermore, the notion that most of the deleterious effects of malaria are explained solely by placental malaria may be too simplistic. Although placental sequestration plays a central role, it is not the only mechanism as systemic maternal responses to malaria parasitaemia are also important. Even if placental parasitisation is the dominant effect, it may only be transient, and systemic maternal parasitaemia may have latent effects in both the mother and the fetus. This is why protection from any parasitisation (however minor, symptomatic or not) is crucial. Formerly, it was best achieved by chemoprophylaxis, but this is no longer possible because of drug resistance. We agree that women must be protected, but if they become infected, they must be treated promptly. Detection and treatment therefore remain essential. Even if bed nets and intermittent preventive treatment (IPT) are deployed effectively (which is usually not the case), many pregnant women will still get infected and will require treatment. Unfortunately, there are no adequate studies of the treatment of malaria in pregnancy in Africa. The pharmacokinetics of drug administration in pregnancy complicates matters substantially. For the treatment of severe and complicated infections, artesunate is the drug of choice in adults3 (note: published after this review), but not artemether as suggested because the absorption of this oil-based intramuscular drug is unreliable in patients with severe disease.

In conclusion, since pregnant women need to be protected from malaria parasitaemias, studies on the safety, the efficacy and the pharmacokinetics of antimalarials are urgently needed for the treatment of both P. falciparum and Plasmodium vivax. As soon as any drugs are identified as suitable and safe for treatment, they should be used for IPT. To encourage such studies, we need to develop a mechanism that addresses the issue of medico-legal liability that partly explains their current absence. The real paradox is that it is perceived by many as unethical to enrol pregnant women in treatment trials, yet quite acceptable to treat them with drugs that are known to be ineffective.

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