Remarks

• Perennial malaria chemoprevention (PMC) schedules should be informed by the age pattern of severe malaria admissions, the duration of protection of the selected drug, and the feasibility and affordability of delivering each additional PMC course (see “Practical info”).
• Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa, including for PMC. Artemisinin-based combination therapies (ACTs) have been effective when used for PMC, but evidence is limited on their safety, efficacy, adherence to multi-day regimens, and cost-effectiveness in the context of PMC.
• Previously, PMC was recommended in infants (<12 months of age) as intermittent preventive treatment in infants (IPTi). Since the initial recommendation, new data have documented the value of malaria chemoprevention in children aged 12 to 24 months.
• The Expanded Programme on Immunization (EPI) platform remains important for delivering PMC. Other methods of delivery can be explored to optimize access to PMC and integration with other health interventions.
• Moderate to high perennial malaria transmission settings are defined as areas with P. falciparum parasite prevalence greater than 10% or an annual parasite incidence greater than 250 per 1000 [29]. These thresholds are indicative and should not be regarded as absolutes for determining applicability of the PMC recommendation.

Practical Info Antimalarial medicine WHO recommends that medicines used for PMC be different from those used as first-line malaria treatment. SP has been widely used for chemoprevention in Africa and has been shown to be efficacious, safe, well tolerated, available and inexpensive. SP was evaluated in 10 trials for PMC, artesunate-amodiaquine (AS+AQ) in one trial, DHAP in one trial, and sulfadoxine-pyrimethamine + artesunate (SP+AS) in one trial [102]. All regimens were found to be effective in reducing clinical malaria. Although ACTs have been effective when used for PMC, evidence is limited on their safety (including potential cumulative toxicity), efficacy, adherence to multi-day regimens, and cost-effectiveness in the context of PMC in young children. A drug regimen that can be administered as a directly observed single dose, such as SP, is preferable to multi-day regimens. Age group The target age group should be identified using local data on the age distribution of malaria admissions and severe disease. Previously, PMC was recommended in infants (<12 months of age) as IPTi based on evidence generated in this age group and an appreciation of the disease burden they bear. Since the initial recommendation, additional data have documented the value of malaria chemoprevention in children aged 12 to 24 months. Three studies evaluated PMC doses in children aged 12 to 15 months [103][104][105], and one study evaluated monthly doses in children up to 24 months [106]. Evidence from seasonal malaria chemoprevention (SMC) programmes, where the age of the target population overlaps with that of PMC, also shows that the impact of chemoprevention on disease burden can be sustained beyond infancy with additional doses. However, there is limited information on the safety and efficacy of malaria chemoprevention in children >15 months of age in perennial transmission settings. 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 PMC. 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 PMC schedule should be informed by the length of protective efficacy of the selected drug, as well as the feasibility of delivering each additional PMC course. SP doses should be given at least one month apart. Eight trials have evaluated a range of 3–6 doses of SP for PMC in the first year of life. Four trials have evaluated 1–12 doses of SP for PMC in the second year of life. The safety and impact of PMC programmes should be routinely monitored. Delivery The EPI platform remains important for delivering PMC, especially in the first year of life, and it may be possible to make use of the EPI or other routine health visits, or establish new contacts to reach children over 1 year of age. Research on alternative approaches for PMC delivery beyond the EPI schedules may be warranted. Consideration should be given to contextual factors such as values and preferences of end-users, costs, coverage and sustainability of alternative delivery platforms. Drug resistance The impact of drug resistance on the protection provided by PMC with SP is currently unclear. The duration of protection of SP has been shown to be 42 days in settings without parasite resistance mutations. This was reduced to 21 days in a setting where 89% of parasites carried the quintuple mutation [107]. In settings with a Pfdhps540 mutation frequency of up to 50%, 3–4 doses of PMC with SP reduced clinical malaria by 30% over the first year of life [107]. However, in the setting where the Pfdhps540 mutation frequency was 89%, no overall protective effect of PMC was observed [107]. The efficacy of SP for treatment is affected by the frequency of mutation-carrying parasites, but there is little evidence that the frequency of molecular markers predicts the efficacy of PMC. Contraindications PMC is not recommended for individuals receiving other forms of malaria chemoprevention (e.g. SMC or MDA). Although PMC and SMC could, in principle, be delivered to different age groups in the same geographical area, for example where there is perennial malaria transmission with seasonal peaks, there is no operational experience of the co-delivery of these strategies. There is currently no experience of co-administration of PMC with the RTS,S/AS01 malaria vaccine. PMC is not recommended in 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 PMC, or those allergic to any of the drugs being used for PMC. PMC with SP should not be given to individuals receiving a sulfa-based medication as treatment or prophylaxis, including co-trimoxazole (trimethoprim–sulfamethoxazole). Other considerations Information about PMC 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 PMC.