title: Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria in the setting of three different chemopreventive regimens.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  600 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  The 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00948896 .
authors: Infectious Diseases Research Collaboration, Mulago Hospital Complex, PO Box 7475, Kampala, Uganda. kapisij@gmail.com.
authors: James
authors: J
authors: Kapisi
authors: Infectious Diseases Research Collaboration, Mulago Hospital Complex, PO Box 7475, Kampala, Uganda. vbigira@gmail.com.
authors: Victor
authors: V
authors: Bigira
authors: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA. tclark@medsfgh.ucsf.edu.
authors: Tamara
authors: T
authors: Clark
authors: Infectious Diseases Research Collaboration, Mulago Hospital Complex, PO Box 7475, Kampala, Uganda. stvobonyo@yahoo.com.
authors: Stephen
authors: S
authors: Kinara
authors: Infectious Diseases Research Collaboration, Mulago Hospital Complex, PO Box 7475, Kampala, Uganda. frita26@gmail.com.
authors: Florence
authors: F
authors: Mwangwa
authors: Department of Pediatrics, Makerere University College of Health Sciences, Kampala, Uganda. achan.jane@gmail.com.
authors: Jane
authors: J
authors: Achan
authors: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda. mkamya@infocom.co.ug.
authors: Moses
authors: M
authors: Kamya
authors: Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, London, UK. seyi.soremekun@lshtm.ac.uk.
authors: Seyi
authors: S
authors: Soremekun
authors: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA. gdorsey@medsfgh.ucsf.edu.
authors: Grant
authors: G
authors: Dorsey
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects*; D018890:Chemoprevention / Q000009:adverse effects* / Q000379:methods*; D002675:Child, Preschool; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D012008:Recurrence; D016896:Treatment Outcome; D014454:Uganda
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes
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