Remarks

• MDA may quickly reduce clinical malaria incidence in settings with moderate to high P. falciparum transmission, butthe effect wanes within 1–3 months. As far as possible, MDA should be implemented as part of a package of malariacontrol measures (including effective case management and appropriate prevention tools and strategies).
• Malaria programmes should judge the suitability of using MDA in their context based on the desired impact, level ofendemicity, and resources required (see “Practical info”).
• There is very limited evidence on the impact of MDA on disease in emergency settings. However, the biological effectsof MDA on disease in non-emergency settings are likely to translate to MDA recipients in emergency settings. The sizeof effect will vary according to the type of emergency and level of disruption to health services, as well as underlyingtransmission intensity, choice of drug, delivery method and other factors.

Practical info Transmission setting The impact of MDA on disease burden varies between high and low malaria transmission settings. In high transmission settings, the impact of MDA on disease is likely to be large and may be cost-effective due to the high background disease burden. However, as transmission intensity and the corresponding disease burden decrease, the impact of MDA also decreases and MDA becomes less cost-effective for disease burden reduction. The effect on other outcomes, parasite incidence and prevalence, and incidence of severe disease also appears to vary by transmission intensity. There are no studies directly comparing the impact of MDA for burden reduction with the impact of more targeted approaches to chemoprevention (e.g. SMC) (Schneider et al unpublished evidence (a)). MDA for burden reduction should be targeted at moderate to high transmission settings, regardless of seasonality. Antimalarial medicine WHO recommends the use of a combination medicine for MDA that is different from that used as 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. A drug regimen that can be administered as a directly observed single dose is preferable to a multi-day regimen. Data were insufficient to discern a specific effect of single-dose primaquine. Available evidence suggests that maximum benefits are seen within 1–3 months after the last round of the intervention (Schneider et al unpublished evidence (a)). Dosage A complete therapeutic course of antimalarials, at doses recommended by the manufacturer, should be given to all eligible adults and children within a defined geographical area. Drug dosage should be determined by weight wherever possible, with dosing according to age only in situations where the person’s weight is unknown. Frequency The frequency of MDA rounds should take into account the local malaria epidemiology, the half-life of the antimalarial used, and the feasibility and cost of delivering each additional round. Consistent with trial data, mathematical models predict that a single round of MDA would lead to an initial decrease in infections, but that the duration of effect would be short-lived. Application of additional rounds is predicted to substantially improve the impact and duration of effect. MDA should not be given to individuals receiving other forms of malaria chemoprevention (e.g. SMC, PMC, or IPTp) (Schneider et al unpublished evidence (a)). Drug resistance There is limited evidence to date on whether MDA accelerates the development and spread of antimalarial drug resistance. However, where data were collected, MDA had little to no effect on drug resistance markers (PfKelch13 and Pfplasmepsin2/3 copy number) among P. falciparum infections (Schneider et al unpublished evidence (a); Plowe unpublished evidence). Contraindications Depending on the medicine chosen, certain population groups may need to be excluded from MDA. These include pregnant women in their first trimester; infants <6 months of age or weighing <5kg; people recently treated with the same medicine; people with a known allergy to the medicine; anyone with severe acute illness or who is unable to take oral medication; people taking medicine known to interact with the medicine used for MDA; and people with specific contraindications to the medicine used [166]. Other considerations Information about MDA should be fully accessible to caregivers, health workers and key stakeholders, such as government officials and religious leaders. As with all health interventions, consent should be obtained, including from the carers of children, prior to administration of MDA.