Discussion
malaria, gastrointestinal intolerability, infection, recrudescence, haemolysis
ADVERSE EVENTS, MALARIA, EVENT, CHRONIC GASTRITIS, INFECTION, FALCIPARUM MALARIA
This multicentre, open-label, superiority randomised trial provides prospective evidence of the efficacy of universal radical cure across different epidemiological settings. In patients presenting with uncomplicated falciparum malaria, high-dose short-course primaquine treatment (total dose 7 mg/kg over 7 days) was safe and relatively well tolerated and reduced the risk of subsequent However, there was marked heterogeneity between sites. In the standard care arm, the risk of The absolute risks of The most recent WHO antimalarial treatment guidelines include a recommendation against high-dose short-course primaquine, citing concerns over serious adverse events at this higher daily dosage including gastrointestinal tolerability.Although co-administration of high-dose primaquine with food is likely to have mitigated the risks of gastrointestinal intolerability, one of the two serious adverse events occurred after the last day of treatment, requiring hospital admission. The event occurred 1 day after completion of treatment and was attributed to underlying chronic gastritis, although this could have been exacerbated by high-dose primaquine. Wider scale roll-out of high-dose primaquine should include caution in patients with premorbid gastrointestinal conditions.The greatest concern for the introduction of shorter more effective radical cure options is that of severe haemolysis in individuals with low G6PD activity.There are substantial logistical challenges in delivering malaria radical cure safely and effectively.Our study has several limitations. First, the study was powered for the overall sample size but not for site-specific analyses. The recruited sample sizes in Bangladesh and Indonesia were small and the primary endpoint was mainly driven by the Ethiopian site, meaning that generalisation of potential benefits of universal radical cure to different endemic settings should be done with caution. Second, the study was not double-blinded and patients in the intervention arm had more visits than those in the standard care arm, which could have contributed to an observation bias for the tolerability assessment, resulting in an increased reporting of adverse events in the intervention arm. Reassuringly, routine questionnaires on day 2 and day 7 highlighted minimal differences between treatment arms. Third, there are no reliable methods to distinguish whether a patient's recurrent infection arises from recrudescence, re-infection, or relapse.Universal radical cure confers substantial individual, public health, and operational benefits in regions co-endemic for 