Remark:

• Programmes implementing reactive drug administration (RDA) should have the capacity to conduct case investigations at the residence to determine the likely location of infection and to identify those individuals co-exposed with the index case.
• Programmes implementing RDA should have the capacity to enumerate and provide antimalarials to the people residing with or near a confirmed malaria case and others that share the same risk of infection.
• The people given antimalarial medicine in an RDA intervention should share the same risk of having acquired infection as the index case or be at risk of acquiring infection from the index case. This includes residents in the same household or neighborhood, co-travellers and co-workers. However, if the infection was imported and the residence is not located in a receptive area, there may be no benefit from RDA.
• Programmes contemplating implementation of RDA for P. vivax should carefully consider how to safely and feasibly administer treatment to prevent relapses.

Practical info When used, RDA should be one of several components of a programme to eliminate or prevent re-establishment of malaria, including intensive follow-up of every case as described in the Framework for malaria elimination [9]. RDA depends on a strong passive surveillance system that detects suspected cases, tests all suspected cases for malaria with a quality-assured parasitological test and investigates all cases at their residence. If these elements are not in place, it is unlikely that an RDA intervention will have any effect on transmission. It is essential to determine the likely location of infection through a case investigation that identifies the location of the person during the likely period of infection in order to understand where or in what group of people the RDA intervention should take place. RDA should be administered to other residents of the same house if the person is determined to have been infected locally. Programmes may consider extending the radius of RDA to neighbours depending on the local epidemiology and ecology of malaria. If the index infection is not likely to have been acquired at the residence, programmes should administer RDA to all people identified as having the same exposure to infection as the index case. People with the same risk of infection are likely to be those who travelled, worked or engaged in leisure activities with the index case. If the infection was classified as imported from elsewhere and the household is not located in a receptive area, there may be no benefit to RDA. Countries that are at very low or low transmission but not yet close to achieving zero indigenous cases should prioritize implementation of RDA and reactive IRS over RACDT. However, RACDT should be added on top of RDA when countries are closer to elimination to strengthen the sensitivity of the surveillance system to monitor progress towards elimination and, post-elimination, to provide additional evidence of a malaria-free status. RDA should be implemented according to standardized operating procedures (SOPs). A household listing of all people residing within the limits of RDA as specified by the SOPs should be developed and verified, along with a list of all people who may have been co-exposed. The RDA programme should seek to provide antimalarial medicine to everyone listed, using different approaches as needed to reach everyone at risk. Achieving high coverage of the targeted population and good adherence to the antimalarial medicine are critical aspects of RDA programmes. RDA programmes ask many asymptomatic, healthy people to take a medicine when they do not feel ill, with the potential for adverse reactions to occur. Improving coverage and adherence requires development of understanding and trust in the institutions implementing the programme. Community engagement is thus a key factor in determining the success of RDA, to improve participation rates and adherence to the full treatment course of the medicine. A complete therapeutic course of antimalarial medicine, at doses recommended by the manufacturer, should be given to all eligible adults and children. Drug dosage should be determined by weight wherever possible, with dosing according to age only in situations where the person’s weight is unknown. The antimalarial medicines chosen for use in RDA should: a) be WHO recommended and prequalified; b) be efficacious against local parasites; c) be different from the medicine used as first-line treatment, where possible c) have a superior safety and tolerability profile; d) provide a longer duration of posttreatment prophylaxis with component medicines that have closely matched pharmacology to reduce the risk of new infections encountering only a single drug; e) have a positive public reputation and acceptability and f) be available and low-cost. Programmes in areas with P. falciparum may consider including a single, low-dose of primaquine in an RDA programmes in order to increase the gametocytocidal effect, although there is no evidence of additional benefit from provision of of single low-dose primaquine in an RDA programme. A drug regimen that can be administered as a directlyobserved single dose is preferred to multi-day regimens. Depending on the medicine chosen, certain population groups may need to be excluded from RDA, such as: pregnant women in their first trimester; infants < 6 months of age or weighing < 5kgs; people recently treated with the same medicine; people with a known allergy to the medicine; anyone with severe acute illness or unable to take oral medication; people taking medication known to interact with the medicine used for RDA; and people with specific contraindications to the medicine used [164]. Although rarely implemented in the same area, RDA should not be given to individuals receiving other forms of malaria chemoprevention (e.g. seasonal malaria chemoprevention, perennial malaria chemoprevention, or intermittent preventive treatment during pregnancy). Programmes contemplating providing medicine for radical cure of P. vivax hypnozoites as part of RDA should carefully consider whether it is feasible to administer this treatment regimen safely, i.e. with testing for G6PD deficiency prior to treatment, an effective pharmacovigilance system and emergency access to blood transfusion services. Programmes should consider whether sufficient coverage and adherence to the full course of radical cure can be achieved.