Abstract
BackgroundThe burden of malaria remains high for children in parts of Africa despite the use of insecticide-treated bed nets (ITNs). Chemoprevention has the potential of reducing the malaria burden; however, limited data exist on the efficacy and safety of anti-malarial therapy in the setting of chemoprevention.Methods600 children 4–5 months of age were enrolled in Tororo, Uganda, an area of high transmission intensity. Participants were given ITNs, and caregivers instructed to bring their child to a study clinic whenever they were ill. Starting at six months of age, 579 were randomized to no chemoprevention, monthly sulphadoxine-pyrimethamine (SP), daily trimethoprim-sulphamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered unsupervised at home until 24 months of age. Episodes of uncomplicated malaria were treated with artemether-lumefantrine (AL) with active follow-up for 28 days. The cumulative risk of recurrent malaria within 84 days and the risk of adverse events within 28 days were compared across study arms using a Cox proportional hazards model and generalized estimating equations, respectively.ResultsA total of 1007, 919, 736, and 451 episodes of malaria were treated in the no chemoprevention, SP, TS, and DP arms, respectively. Only 19 (0.6%) treatments were for severe malaria. Early response to therapy with AL was excellent with 96.5% fever clearance and 99.4% parasite clearance by day 3. However, over 50% of AL treatments were followed by recurrent parasitaemia within 28 days. Compared to the no chemoprevention arm, the cumulative risk of recurrent malaria within 84 days following treatment of uncomplicated malaria with AL was significantly lower in the DP arm (HR = 0.77, 95% CI 0.63-0.95, p = 0.01) but not the SP or TS arms. Compared to the no chemoprevention arm, none of the chemopreventive regimens were associated with an increased risk of adverse events following treatment of malaria with AL.ConclusionsThe risk of severe malaria was very low in this cohort of young children living in a high transmission setting. In the setting of chemoprevention, treatment of uncomplicated malaria with AL was safe and efficacious, with moderate protection against recurrent malaria among children assigned monthly DP.Trial registrationClinicalTrials.gov NCT00948896.
Highlights
The burden of malaria remains high for children in parts of Africa despite the use of insecticidetreated bed nets (ITNs)
The risk of severe malaria was very low in this cohort of young children living in a high transmission setting
Efficacy and safety outcomes were assessed at the level of each treatment of uncomplicated malaria with AL. 28-day efficacy outcomes included fever and parasite clearance by day 3, appearance of gametocytes not present on day 0, haemoglobin recovery, and WHO treatment outcomes using a standardized classification system [5]. 28-day safety outcomes were based on the identification of adverse events not present on day 0 or of increased severity compared to day 0
Summary
The burden of malaria remains high for children in parts of Africa despite the use of insecticidetreated bed nets (ITNs). The burden of malaria remains unacceptably high in some parts of sub-Saharan Africa despite the scaling up of control interventions including provision of insecticidetreated bed nets (ITNs), indoor residual spraying of insecticide, and prompt malaria case management with artemisinin-based combination therapy (ACT). In 2012, there were an estimated 207 million cases and 627,000 deaths, with 80% of cases and 90% of deaths occurring in Africa, primarily in children under five years of age [1] With such high morbidity and mortality, achieving Millennium Development Goals 4 and 6 by 2015 will be unlikely without additional control measures, especially in areas of Africa with persistent high malaria transmission intensity. Alternative drugs and/or approaches are needed in areas where the prevalence of resistance to antifolate drugs is high or malaria transmission occurs throughout the year
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
