Remarks

• Intermittent preventive treatment in school-aged children (IPTsc) has been evaluated in children aged 5–15 years. Theburden of malaria and benefits of IPTsc may vary across this age range, but evidence is limited.
• National malaria programmes can consider IPTsc if resources allow for its introduction among school-aged children withoutcompromising chemoprevention interventions for those carrying the highest burden of severe disease, such as children < 5years old.
• Schools may provide a low-cost means to deliver chemoprevention to school-aged children. However seasonal variation inmalaria transmission and the timing of school terms, as well as equity concerns, may mean alternative delivery channelsare needed to maximize impact.
• First- and second-line malaria treatments should not be used for IPTsc if safe and effective alternatives are available (see“Practical info”).
• The dosing schedule for IPTsc should be informed by the local malaria epidemiology and timed to give protection duringthe period of greatest malaria risk (see “Practical info”).
• Moderate to high malaria transmission settings are defined as areas with P. falciparum parasite prevalence greater than10% or an annual parasite incidence greater than 250 per 1000 [30]. These thresholds are indicative and should not beregarded as absolutes for determining applicability of the IPTsc recommendation.

Practical info Antimalarial medicine Drug regimens evaluated for IPTsc and found to be effective include SP combined with an aminoquinoline (either AQ or piperaquine), SP+AS, and artemisinin-based combination therapy including an aminoquinoline (AS-AQ or DHAP)1 . SP+AQ has been widely used for chemoprevention in West Africa and has been shown to be efficacious, safe, well tolerated, available and inexpensive. In order to reduce the risk of drug resistance to life-saving drugs, first- and second-line malaria treatments should not be used for IPTsc if safe and effective alternatives are available. The possibility of interactions with other drugs delivered as part of school health programmes should be considered. Age group The target age group should be identified using local data on the age distribution of malaria admissions and severe disease. As young children (≤ 59 months) are the most vulnerable to severe malaria, chemoprevention interventions to protect this age group should be prioritized over those for school-aged children. If resources allow for introduction of chemoprevention for school-aged children without compromising chemoprevention in younger children, national malaria programmes can consider IPTsc. The majority of IPTsc studies have evaluated the intervention in children under 15 years old. There is some evidence of a stronger effect on malaria-related anaemia in children younger than 10 years versus those who are 10–15 years. However, the effect of IPTsc on P. falciparum infection was similar across these two age groups. If older age groups are included in IPTsc, particular consideration should be given on how best to include girls with a history of menarche. Certain antimalarials should not be given for chemoprevention without first confirming pregnancy status. There is insufficient information on the safety, efficacy and pharmacokinetics of most antimalarial agents in pregnancy, particularly during the first trimester. In IPTsc studies that have included girls with a history of menarche, pregnancy status has been determined either through self-reporting or the use of pregnancy tests. Further research is needed on how best to safely include girls of reproductive age in IPTsc. Dosage School-aged children should be given a complete course of antimalarials at their recommended treatment dose as IPTsc. 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 or cannot be determined. Frequency The IPTsc schedule should be informed by the local malaria epidemiology, particularly transmission intensity and seasonality, the pharmacokinetics of the drug used, and the feasibility of delivering each additional IPTsc course. IPTsc should be timed to give protection during the period of greatest malaria risk. Most trials provided IPTsc monthly or each term. In settings where PMC is being provided, IPTsc may need to be given at regular intervals throughout the year. In perennial transmission settings, the higher the transmission intensity, the greater the expected value of drugs with longer half-lives or more frequent dosing, which will increase the proportion of time-at-risk protected by IPTsc. If IPTsc cannot be maintained throughout the year in perennial transmission settings due to resource constraints, IPTsc may be timed to provide protection during transmission peaks. Delivery IPTsc can be delivered either through schools or through community-based approaches. The method of delivery should consider the local epidemiology of malaria and whether school-based delivery will offer protection during the period of greatest malaria risk. All types of schools that cater to children aged up to 15 years in the target area should be included for IPTsc delivery. National malaria programmes may be able to work with existing health programmes targeting school-aged children to facilitate delivery of IPTsc. Children not attending school are likely to be at highest risk of malaria and, if school attendance is not high, special efforts may be needed to target children not attending school. In seasonal transmission areas, delivery in schools may not align with peak malaria transmission and thus it may be more appropriate to utilize existing community-based approaches to reach school-aged children, such as those strategies used for SMC. Care is needed to ensure adequate communication with communities, teachers, caregivers and children to maximize understanding and acceptability in these key stakeholder groups. If older age groups are included in IPTsc administration, communication with key stakeholders should pay attention to the inclusion of girls of reproductive age (see ‘Age group’ above). Drug resistance The impact of drug resistance on the protection provided by IPTsc is currently unclear. A re-analysis of data on resistance markers following monthly IPTsc found no suggestion of an increased prevalence of any resistance markers following DHAP administration2 (Plowe unpublished evidence). A review of the relationship between the different chemoprevention strategies (IPTp, PMC, SMC, MDA, IPTsc) and drug resistance concluded that malaria chemoprevention as used to date does not inevitably lead to an increase in resistance, and even high rates of resistance may not necessarily impair chemoprevention efficacy (Plowe unpublished evidence). However, expanded use of antimalarial medicines may increase resistance and eventually undermine efficacy. Using different drugs for chemoprevention and treatment, and combining drugs with counteracting resistance mechanisms may help to preserve efficacy (Plowe unpublished evidence). Contraindications IPTsc is not recommended for individuals receiving other forms of malaria chemoprevention (e.g. SMC or MDA). Children with sickle cell disease should be included in IPTsc unless they already receive regular chemoprevention due to sickle cell disease. Co-delivery of IPTsc alongside other school health programmes should consider drug manufacturers’ guidance regarding whether IPTsc can be safely given with other medicines and whether there are any additional contraindications as a result. Additionally, there is a need to consider how to include girls of reproductive age who should not be given certain antimalarials for prophylaxis without first confirming that they are not pregnant (see "Age group' above for further information). IPTsc is not recommended in children with severe acute illness, those unable to take oral medication, children who during the last 30 days received a dose of any drug being used for IPTsc, or those allergic to any of the drugs being used for IPTsc. IPTscSP should not be given to individuals receiving a sulfa-based medication as treatment or prophylaxis, including co-trimoxazole (trimethoprim–sulfamethoxazole) for HIV. Other considerations Information about IPTsc should be fully accessible to school-aged children, their caregivers and key stakeholders, such as teachers. As with all health interventions, consent should be obtained from the caregiver on behalf of the child prior to administration of IPTsc and, depending on age, from the child themselves.