Editorial: Maternal malaria: time for action

Among human parasitic diseases, malaria remains the world’s most important cause of morbidity and mortality. The impact of malaria on health and on development is huge and, because of the spread of drug resistance in P. falciparum, it is worsening. In all endemic regions, children and pregnant women are the two groups mostly at risk of severe disease and death. The true magnitude of the burden of maternal malaria is unknown, but recent reports indicate that it may be much higher than previously thought. For example recently, falciparum malaria was identified as the leading cause of maternal death in a hospital study in Mozambique (Granja et al. 2001) and in a population in Zimbabwe (Rutgers 2001). Falciparum malaria is particularly lethal in pregnant women during epidemics. Through the adverse effects of malaria on birthweight and prematurity, maternal infection also results in excess infant mortality (Luxemburger et al. 2001; Steketee et al. 2001). In areas of high stable transmission, the most visible impact of malaria on maternal health is severe anaemia, an important contributor to maternal mortality (Brabin et al. 2001). Prevention strategies include vector control (impregnated bed nets) and chemoprophylaxis (where still effective) or intermittent preventive treatment (IPT). In areas of low or unstable transmission, severe disease is more common and early detection and prompt treatment are essential to reduce mortality. In all situations antimalarial drugs play the central role. It is recommended that pregnant women living in malaria-endemic areas receive antimalarial chemoprophylaxis – but with what drug? Chloroquine, still the most widely recommended and used antimalarial for pregnant women in Africa, has become ineffective against P. falciparum in most endemic countries. There is no universally effective drug, with a similarly good safety profile in pregnancy, to replace it. This is partly the result of the systematic exclusion of pregnant women from any drug development programme, because of the fear of potential adverse effects on the unborn child. In a world increasingly driven by economic forces, the spectre of liability looms over the pharmaceutical industry and also over international institutions. The debate on antimalarials for pregnant women has shifted from Which drug has the most favourable risk-benefit ratio for the mother? to Who is responsible if an unwanted side effect of the drug on the foetus is discovered? In endemic areas of Africa, most of the pregnant women remain unprotected against malaria. Those who are treated, often receive ineffective drugs. These are difficult times for public health authorities in many malaria-affected countries, as they come under increasing pressure to change antimalarial drug policies. In this issue of TMIH, Newman and colleagues present a comprehensive analysis of available antimalarials, with the aim of helping maternal malaria prevention programmes in sub-Saharan Africa. Importantly, the authors take into account not only the efficacy of various drug regimens (using the data on children as a proxy of the efficacy in pregnancy, because there are usually no data for pregnant women) but also their effectiveness : a combination of efficacy with availability, acceptability, affordability, and deliverability. It was concluded that, the best possible option to date is to use intermittent presumptive therapy (IPT) with sulfadoxine-pyrimethamine (SP). Five studies have been conducted, all in high transmission settings in East Africa (two in Malawi and three in Kenya). These have shown that two treatment doses of SP given to HIV-negative mothers during pregnancy, can reduce maternal anaemia (significant in three of the four studies in which this was evaluated) and low birth weight (two of four studies) (Schultz et al. 1994; Parise et al. 1998; Verhoeff et al. 1998; Shulman et al. 1999). Three doses are needed for HIV-positive mothers. On the basis of these results, IPT is now recommended for pregnant women by WHO (2000) and more recently, has been proposed for infants and children (Pasha et al. 2003). But resistance to SP has taken hold in East Africa, where 28-day failure rates range between 30 and 60% and it is spreading rapidly across the continent; for example SP failed to cure more than 50% of the treated children in a recent study from Liberia (Checchi et al. 2002). Newman et al. describe the therapeutic efficacy of SP as being fair to good in most of Africa, but this may be over-optimistic. Since the four pivotal Tropical Medicine and International Health