Intermittent Presumptive Treatment for Malaria

I ntermittent presumptive treatment (IPT) in pregnancy involves giving a curative treatment dose of an effective antimalarial drug at predefi ned intervals during pregnancy. IPT in pregnancy was fi rst introduced in areas of high malaria transmission as a measure to reduce the adverse impact of Plasmodium falciparum malaria based on trials showing that IPT could reduce anaemia in young children and also malaria episodes in infants, it was extended as a measure to reduce morbidity and mortality in the fi rst year of life [9,10,11,12]. Antimalarial chemoprophylaxis for pregnant women living in endemic areas has been recommended for many years, but in practice has been limited to the use of chloroquine and pyrimethamine [13,14]. Unfortunately, there are few places left in the world where these drugs can still be relied upon to prevent P. falciparum malaria. There are insuffi cient safety data on the newer antimalarials to warrant their systematic use in pregnant women. IPT with sulphadoxine-pyrimethamine (SP) has been introduced as an alternative. Antimalarial chemoprophylaxis in young children has been shown to reduce the adverse impact of P. falciparum malaria [15,16,17], but this intervention never obtained the same endorsement as chemoprophylaxis in pregnancy. Five randomised trials of IPT in pregnancy in East Africa have been reported [1,2,3,4,5], all with SP, all in high-transmission settings, and all done between 1992 and 1999 (Table S1). The alarming recent increase in resistance to SP in Africa confounds the cost-effectiveness assessments upon which subsequent policy recommendations for IPT in pregnancy were based [18,19]. There is no consensus on how IPT works, making planning diffi cult. This article argues that IPT provides mainly intermittent suppressive chemoprophylaxis (as opposed to treatment effect alone or some other magical effects which have never been specifi ed). If this is correct dosing schedules should be individualised for each antimalarial depending on the drug's pharmacokinetic and pharmacodynamic properties. As increasing resistance to SP must seriously compromise IPT regimens based on this drug, the evaluation of available new effective antimalarials is needed urgently, in both high-and low-transmission areas. Pharmacokinetics After a treatment dose of SP (25 mg sulfadoxine/1.25 mg pyrimethamine per kilogram body weight), plasma concentrations of pyrimethamine (half-life, 3 days) and sulfadoxine (half-life, 7 days) decline log-linearly [20,21]. The antimalarial effect depends on synergy between the two components, but the effect from one treatment dose can last as long as 60 days with fully sensitive P. falciparum [20,21]. …