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Background Long-acting artemisinin-based combination therapy (LACT) offers the potential to prevent recurrent malaria attacks in highly exposed children. However, it is not clear where this advantage will be most important, and deployment of these drugs is not rationalized on this basis. Methods To understand where post-treatment prophylaxis would be most beneficial, the relationship between seasonality, transmission intensity and the interval between malaria episodes was explored using data from six cohort studies in West Africa and an individual-based malaria transmission model. The total number of recurrent malaria cases per 1000 child-years at risk, and the fraction of the total annual burden that this represents were estimated for sub-Saharan Africa. Results In settings where prevalence is less than 10 %, repeat malaria episodes constitute a small fraction of the total burden, and few repeat episodes occur within the window of protection provided by currently available drugs. However, in higher transmission settings, and particularly in high transmission settings with highly seasonal transmission, repeat malaria becomes increasingly important, with up to 20 % of the total clinical burden in children estimated to be due to repeat episodes within 4 weeks of a prior attack. Conclusion At a given level of transmission intensity and annual incidence, the concentration of repeat malaria episodes in time, and consequently the protection from LACT is highest in the most seasonal areas. As a result, the degree of seasonality, in addition to the overall intensity of transmission, should be considered by policy makers when deciding between ACT that differ in their duration of post-treatment prophylaxis. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0839-4) contains supplementary material, which is available to authorized users.

Background The use of artemisinin-based combination therapy (ACT) is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT - artesunate plus amodiaquine (ASAQ) and artemether-lumefantrine (AL) - in subsequent episodes of Plasmodium falciparum malaria. Methods A randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR) after polymerase chain reaction (PCR) correction on day 28 for the first episode. Results A total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182) and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182), PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03). No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during treatment with no clinical consequence. Conclusions Study results confirmed the satisfactory efficacy and safety profile of ASAQ and AL. Moreover, in patients who were treated at least twice, repeated administration of ASAQ or AL did not identify any major safety issues. Trial registration ClinicalTrials.gov identifier NCT00540410.