Remarks

• Eligibility for seasonal malaria chemoprevention (SMC) is defined by the seasonality of malaria transmission and agegroups at risk of severe malaria. Thresholds for assessing these criteria change over time and location. Malariaprogrammes should assess the suitability of SMC based on the local malaria epidemiology and available funding (see“Practical info”). The added value of a seasonally targeted intervention is likely to be greatest where transmission isintensely seasonal.
• Monthly cycles of sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) have been widely used for SMC in Africanchildren under 5 years old and have been shown to be efficacious, safe, well tolerated, available and inexpensive (Thwing et al unpublished evidence).

Practical info Antimalarial medicine WHO recommends a combination medicine for SMC that is different from that used for first-line malaria treatment. The component medicines should have closely matched pharmacology, such that no component is present in the absence of other components for more than a minimal amount of time in order to reduce the risk of new infections encountering only a single drug. SP+AQ has been evaluated in 12 studies of SMC and has been widely used for SMC in Africa. SP+AQ has been shown to be efficacious, safe, well tolerated, available and inexpensive (Thwing et al unpublished evidence). The prevalence of molecular markers of resistance to SP+AQ was low in the general population before and two years after SMC implementation in seven countries in west and central Africa (Bhattarai et al unpublished evidence). Safety and efficacy have been evaluated for several other drug combinations, but the lack of widescale implementation means that fewer data are available on the potential risks of cumulative toxicity and impact on drug resistance. Age group Most research studies have evaluated SMC in children aged 3–59 months. SMC given to children <5 years old reduced the risk of clinical malaria by almost three quarters (risk ratio: 0.27; 95% CI: 0.25–0.29) during the transmission season (Thwing et al unpublished evidence). SMC has also been shown to reduce the incidence of clinical malaria in children <10 years old. Studies conducted in one country comparing the effect of SMC among children <5 years old with that in children 5–9 years old found no difference in the effect size for malaria incidence or prevalence, severe malaria, or anaemia (Thwing et al unpublished evidence). The age group targeted for SMC should be informed by the local age pattern of severe malaria admissions. The cost-effectiveness of SMC will become less favourable as programmes expand to age groups at lower risk of severe disease and areas of lower malaria transmission [141]. Dosage Children in age groups at increased risk of severe disease should be given a complete course of antimalarials, at their recommended treatment dose, as SMC. The drug dosage should be determined by the child’s weight wherever possible, with dosing according to age only in situations where the child’s weight is unknown. Frequency The number of cycles should be informed by the duration of the high-transmission season, based on the local malaria epidemiology, and the length of preventive efficacy of the selected drug combination. SMC should be used to protect children during the entire high-transmission season. Current evidence supports monthly administration of SMC for 3–4 cycles in shorter transmission settings, and up to six cycles have been evaluated in settings with longer transmission seasons (Thwing et al unpublished evidence). Delivery SMC can be provided through door-to-door or fixed-point delivery. A study in Mali found that door-to-door delivery achieved significantly higher coverage than fixed-point delivery (76.1% versus 62.2%, p = 0.0028) [142]. Further studies in Mali and Gambia have supported that door-to-door delivery can achieve high coverage [143][144]. Studies found similar SMC coverage in children given directly observed treatment compared to non-directly observed treatment [142][143]. Drug resistance While some prospective trials and ecological studies of SMC with SP+AQ in West Africa have reported increased prevalence of the dhfr/dhps quadruple and quintuple mutants, other studies have found no evidence of selection. No evidence has been reported of SMC being followed by increased prevalence of the higher level resistance mutations that most severely impair curative SP efficacy, nor does SMC appear to select for parasites carrying mutations associated with diminished AQ susceptibility (Plowe unpublished evidence). Contraindications SMC is not recommended for individuals receiving other forms of malaria chemoprevention (e.g. MDA or PMC). Although PMC and SMC could, in principle, be delivered to different age groups in the same geographical area (e.g. where there is perennial malaria transmission with seasonal peaks), there is no operational experience of the co-delivery of these strategies. SMC is not recommended for children with severe acute illness or those who are unable to take oral medication, children who during the last 30 days received a dose of any of the drugs being used for SMC, or children with an allergy to any of the drugs being used for SMC. Children should not be given SMC including SP if they are receiving a sulfa-based medication as treatment or prophylaxis, including co-trimoxazole (trimethoprim–sulfamethoxazole). Other considerations Information about SMC should be fully accessible to caregivers and key stakeholders, such as government officials and religious leaders. As with all health interventions, consent should be obtained from the caregiver on behalf of the child prior to administration of SMC.