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BACKGROUND In treating malaria in Uganda, artemether-lumefantrine (AL) has been associated with a lower risk of recurrent parasitemia, compared with artesunate-amodiaquine (AS/AQ), but changing treatment practices may have altered parasite susceptibility. METHODS We enrolled 602 children aged 6-59 months with uncomplicated falciparum malaria from 3 health centers in 2013-2014 and randomly assigned them to receive treatment with AS/AQ or AL. Primary outcomes were risks of recurrent parasitemia within 28 days, with or without adjustment to distinguish recrudescence from new infection. Drug safety and tolerability and Plasmodium falciparum resistance-mediating polymorphisms were assessed. RESULTS Of enrolled patients, 594 (98.7%) completed the 28-day study. Risks of recurrent parasitemia were lower with AS/AQ at all 3 sites (overall, 28.6% vs 44.6%; P < .001). Recrudescences were uncommon, and all occurred after AL treatment (0% vs 2.5%; P = .006). Recovery of the hemoglobin level was greater with AS/AQ (1.73 vs 1.39 g/dL; P = .04). Both regimens were well tolerated; serious adverse events were uncommon (1.7% in the AS/AQ group and 1.0% in the AL group). AS/AQ selected for mutant pfcrt/pfmdr1 polymorphisms and AL for wild-type pfcrt/pfmdr1 polymorphisms associated with altered drug susceptibility. CONCLUSIONS AS/AQ treatment was followed by fewer recurrences than AL treatment, contrasting with older data. Each regimen selected for polymorphisms associated with decreased treatment response. Research should consider multiple or rotating regimens to maintain treatment efficacies.

Northern Uganda hosts a large population of refugees from South Sudan, and malaria is one of the major health problems in the area. In 2015, intermittent preventive treatment for malaria (IPTc) was implemented in two refugee camps among children aged 6 months to 14 years. Three distributions of dihydroartemisinin–piperaquine (DP) were conducted at 8-week intervals. The first dose was directly administered at IPTc distribution sites and the second and third doses were given to caregivers to administer at home. A multi-faceted evaluation was implemented, including coverage surveys, malaria prevalence surveys, reinforced surveillance, and pharmacovigilance. Programme coverage exceeded 90% during all three distributions with a total of 40,611 participants. Compared to same period during the previous year (only available data), the incidence of malaria in the target populations was reduced (IRR 0.73, 95% CI 0.69–0.77 among children under 5 years old; IRR 0.70, 95% CI 0.67–0.72 among children aged 5–14 years). Among those not targeted for intervention, the incidence between the 2 years increased (IRR 1.49, 95% CI 1.42–1.56). Cross-sectional surveys showed a prevalence of parasitaemia (microscopy or PCR) of 12.9–16.4% (95% CI 12.6–19.3) during the intervention, with the highest prevalence among children aged 5–14 years, but with a large increase 8 weeks after the final distribution. A total of 57 adverse events were reported during the intervention period, including one severe adverse event (death from varicella). Adverse events were of mild to moderate severity, and were mainly dermatologic and gastrointestinal. This is the first documentation of an IPTc programme in a refugee camp. The positive impact of DP on the incidence of malaria, together with its favourable safety profile, should lead to further use of IPTc in similar settings. Expanding coverage groups and decreasing intervals between distributions might provide more benefit, but would need to be balanced with the operational implications of a broader, more frequent distribution schedule.

Background The integrated approach to malaria prevention which advocates use of several methods in a holistic manner is being explored to complement existing strategies. A pilot project that promoted integrated malaria prevention established 40 demonstration households using the approach. As part of impact evaluation of the project 2 years after implementation, the experiences of these households using integrated malaria prevention were assessed. Methods A qualitative cross-sectional survey was carried out in Wakiso district, Uganda which involved 40 in-depth interviews among households implementing integrated malaria prevention. The study assessed practices on malaria prevention, benefits and challenges of using integrated malaria prevention, preference of malaria prevention methods, and impact of the demonstration households on the community. Thematic analysis was employed using Atlas ti software. Results The households continued to use many of the malaria prevention methods in the integrated approach including sleeping under long-lasting insecticidal nets, screening in windows and ventilators, removing mosquito breeding sites, and closing of doors early in the evenings. The major benefits reported from using integrated malaria prevention were reduction in mosquito populations in their houses and less occurrence of malaria particularly among children. Although several community members learnt about and admired various malaria prevention methods from the demonstration households especially screening in windows and ventilators, the majority could not afford to implement some of them due to lack of resources. The main challenge established in using integrated malaria prevention was the much time required to implement the several methods some of which had to be done regularly such as early closing of windows. In addition, complacency had led to some households not utilizing a number of methods in the integrated approach because of using others. Conclusion Use of the integrated approach to malaria prevention benefited the demonstration households mainly through observed reduction in mosquitoes indoors and malaria occurrence hence could be promoted in other areas. Other studies to quantify the protective effect of integrated malaria prevention particularly regarding malaria prevalence and contribution of each of the methods are required.