Remarks

• Persons given antimalarials should be those with increased risk of infection compared to the general population and their infections should constitute a large proportion of the parasite reservoir in the area.
• The factors identifying individuals or groups at increased risk of infection should be easy to recognise, thereby improving the acceptability and feasibility of the intervention.
• Programmes considering implementing targeted drug administration for P. vivax should carefully consider how to safely and feasibly administer treatment to prevent relapses.
• Care should be taken to avoid stigmatizing groups at increased risk of infection.
• Additional complementary strategies to eliminate or prevent re-establishment of malaria transmission should be in place.

Practical Info TDA depends on detailed, recent knowledge of the epidemiology and ecology of malaria in an area. This knowledge is generally based on a strong passive surveillance system that can detect all suspected cases, diagnose infections, collect and analyse case-based data and characterize cases according to potential risk factors. (The ability to conduct case investigations at the home of the person diagnosed with malaria is not a requirement for a TDA programme but could potentially improve the quality of the data collected.) The persons given antimalarials in a TDA programme should be those with an increased risk of infection compared to the general population. This could include individuals in key demographic groups or with certain occupations or behaviours that are known to be associated with increased infection rates. Additionally, data from the surveillance system should demonstrate that infections in these individuals are likely to comprise a large proportion of the infectious reservoir in the area. Finally, the characteristics or risk factors that define the group at increased risk of infection should be easily recognizable or identifiable; if not, the TDA programme will be more challenging to implement and possibly less acceptable to stakeholders. Malaria elimination programmes implementing TDA should recognize that, as areas approach elimination, malaria infections become more concentrated in certain geographies and populations that may already be socially disadvantaged. This includes migrants, displaced persons, ethnic minorities and poor rural communities. A TDA programme should actively seek to prevent further adverse social impact on these groups. Language choices can frame the way that groups are perceived, and TDA programmes should avoid labelling groups of people as “reservoirs" of infection or “hot” populations. Referring to chemoprevention for malaria in higher-risk “situations” rather than higher-risk “groups” can shift the focus away from scapegoating certain populations. By engaging communities affected by malaria in elimination settings, including those that may be socially marginalized, malaria elimination programmes can improve their understanding of local social dynamics and identify strategies to provide better services to people at risk of malaria infection. TDA programmes should monitor the social impact of their interventions to determine if stigma is occurring to any malaria-affected populations and to determine whether their efforts to avoid stigma are working. Achieving high coverage of the affected population and good adherence to the antimalarial medicine are critical aspects of TDA programmes. TDA 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 TDA, 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 TDA 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 lowcost. Programmes in areas with P. falciparum may consider including a single, low-dose of primaquine in TDA programmes in order to increase the gametocytocidal effect, although no evidence of an additional benefit from provision of single lowdose primaquine in a TDA programme was reviewed. A drug regimen that can be administered as a directly-observed single dose is preferred to multi-day regimens. Depending on the medicine chosen, certain population groups may need to be excluded from TDA, 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 TDA; and people with specific contraindications to the medicine used. Although rarely implemented in the same area, TDA 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) [137]. Programmes contemplating providing medicine for radical cure of P. vivax hypnozoites as part of TDA programme 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.