Remarks

• Sulfadoxine-pyrimethamine (SP) has been widely used for malaria chemoprevention during pregnancy and remains effective in improving key pregnancy outcomes.
• IPTp-SP should start as early as possible in the second trimester and not before week 13 of pregnancy.
• Doses should be given at least one month apart, with the objective of ensuring that at least three doses are received.
• Antenatal care (ANC) contacts remain an important platform for delivering IPTp. Where inequities in ANC service and reach exist, other delivery methods (such as the use of community health workers) may be explored, ensuring that ANC attendance is maintained and underlying inequities in ANC delivery are addressed.
• IPTp is generally highly cost-effective, widely accepted, feasible for delivery and justified by a large body of evidence generated over several decades.

Practical info Antimalarial medicine WHO recommends that the medicines used for IPTp be different from those used as first-line malaria treatment. SP has been widely used for chemoprevention during pregnancy and has been shown to be efficacious, safe, well tolerated, available and inexpensive. A drug regimen that can be administered as a directly observed single dose, such as SP, is preferable to a multi-day regimen. The Guideline Development Group did not formally consider alternative drug regimens to SP for IPTp, or their associated costs. However, recent studies of dihydroartemisinin-piperaquine (DHAP) in areas of high SP resistance have shown that, although superior to SP in reducing malaria during pregnancy, the use of DHAP did not translate into better pregnancy outcomes; SP was associated with better fetal growth, resulting in higher mean birthweights in all gravidae (Gutman et al unpublished evidence (a)). Transmission In areas of moderate to high P. falciparum transmission, IPTp-SP should be given to all pregnant women. Whether there continues to be a role for IPTp in areas where malaria transmission has fallen to low levels is uncertain. There is evidence that even in areas with PfPR2-10 < 3%, IPTp-SP reduces maternal anaemia and may reduce low birthweight, as well as maternal and placental infection (Gutman et al unpublished evidence (a)). Some of these effects may not be due to the effects of IPTp-SP on malaria. There is currently insufficient data to define the level of transmission below which IPTp-SP may cease to be cost-effective. Challenges of IPTp reintroduction after withdrawal caution against discontinuing IPTp-SP following a recent reduction in malaria transmission. Pregnancy IPTp improves a wide range of outcomes in women in their first and second pregnancies, including maternal and placental infection, maternal anaemia and low birthweight (Gutman et al unpublished evidence (a)). There is now evidence that IPTp also reduces maternal infection in third or subsequent pregnancies, but there are currently too few trials to evaluate effects on other outcomes in these women (Gutman et al unpublished evidence (a)). Administering IPTp to all pregnant women regardless of number of pregnancies facilitates ease of IPTp implementation for health workers. Dosage IPTp-SP should ideally be administered as directly observed therapy (DOT) with three tablets of SP (each tablet containing 500 mg/25 mg SP), for the total required dosage of 1500 mg/75 mg SP. Schedule IPTp-SP should not be given before week 13 of pregnancy due to an increased risk of fetal malformation. IPTp-SP should start in the second trimester and doses should be given at each scheduled ANC contact until the time of delivery, provided that doses are at least one month apart. At least three doses of IPTp-SP should be received during pregnancy. Delivery ANC contacts remain an important platform for delivering IPTp, and so inequities in ANC service and reach should be addressed. Research on alternative approaches to IPTp delivery (e.g. through community health workers) may identify opportunities to increase coverage, while ensuring that ANC attendance is maintained. This may be useful for supporting IPTp delivery while measures to address ANC inequities are implemented. Consideration should be given to contextual factors such as the values and preferences of end-users, costs, coverage and sustainability of alternative delivery platforms. Drug resistance IPTp-SP appears to select for antifolate resistance mutations associated with low to moderate increases in drug resistance. However, there is no convincing evidence of selection favouring key mutations, such as dhpsA581G, which is associated with the loss of IPTp-SP efficacy (Plowe unpublished evidence). There is also insufficient evidence to withhold IPTp-SP in areas where the prevalence of dhpsA581G exceeds a threshold of 10% (Plowe unpublished evidence). Although the ability of IPTp-SP to clear existing infections and prevent new ones is compromised in areas of high to very high resistance, the intervention still reduces low birthweight and maternal anaemia. Consequently, IPTp-SP should continue to be used in areas of high SP resistance until more effective alternatives for malaria chemoprevention are found. Contraindications IPTp is not recommended for pregnant women before week 13 of pregnancy, or those with severe acute illness, or who are unable to take oral medication, or women who during the last 30 days received a dose of any of the drugs being used for IPTp, or those allergic to any of the components of SP. IPTp-SP should not be given to individuals receiving a sulfa-based medicine as treatment or prophylaxis, including co-trimoxazole (trimethoprim–sulfamethoxazole) for HIV. High doses of folic acid (daily dose ≥ 5 mg) have been shown to counteract the efficacy of SP as an antimalarial, and only low-dose formulations (i.e. 0.4 mg daily) should be coadministered with SP. Other considerations Information about IPTp should be fully accessible to pregnant women. As with all health interventions, consent should be obtained from the pregnant woman prior to administering IPTp.