title: Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  A single low dose (0.25 mg/kg) of primaquine is recommended as a gametocytocide in combination with artemisinin-based combination therapies for Plasmodium falciparum but its effect on post-treatment gametocyte circulation and infectiousness to mosquitoes has not been quantified.
  
  
  METHODS
  In this randomised, double-blind, placebo-controlled trial, 360 asymptomatic parasitaemic children aged 2-15 years were enrolled and assigned to receive: artemether-lumefantrine (AL) and a dose of placebo; AL and a 0.25 mg/kg primaquine dose; or AL and a 0.40 mg/kg primaquine dose. On days 0, 2, 3, 7, 10 and 14, gametocytes were detected and quantified by microscopy, Pfs25 mRNA quantitative nucleic acid sequence based amplification (QT-NASBA), and quantitative reverse-transcriptase PCR (qRT-PCR). For a subset of participants, pre- and post-treatment infectiousness was assessed by mosquito feeding assays on days -1, 3, 7, 10 and 14.
  
  
  RESULTS
  Both primaquine arms had lower gametocyte prevalences after day 3 compared to the placebo arm, regardless of gametocyte detection method. The mean (95% confidence interval) number of days to gametocyte clearance in children with patent gametocytes on day 0 (N = 150) was 19.7 (14.6 - 24.8), 7.7 (6.3 - 9.1) and 8.2 (6.7 - 9.6) for the AL-placebo, the 0.25 mg/kg primaquine dose and the 0.40 mg/kg primaquine dose arms, respectively. While 38.0% (30/79) of selected gametocytaemic individuals were infectious before treatment, only 1/251 participant, from the AL-placebo group, infected mosquitoes after treatment.
  
  
  CONCLUSIONS
  We observed similar gametocyte clearance rates after 0.25 and 0.40 mg/kg primaquine doses. Infectivity to mosquitoes after AL was very low and absent in primaquine arms. CLINICALTRIALS.
  NCT01935882.
authors.affiliation: Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK. bronner.goncalves@lshtm.ac.uk.
authors.forename: Bronner P
authors.initials: BP
authors.lastname: Gonçalves
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. vtalfred@fasonet.bf.
authors.forename: Alfred B
authors.initials: AB
authors.lastname: Tiono
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. aouedraogo.cnrfp@fasonet.bf.
authors.forename: Alphonse
authors.initials: A
authors.lastname: Ouédraogo
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. guelbeogo.cnrfp@fasonet.bf.
authors.forename: Wamdaogo M
authors.initials: WM
authors.lastname: Guelbéogo
authors.affiliation: MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. john.bradley@lshtm.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Bradley
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. issanebie.cnlp@fasonet.bf.
authors.forename: Issa
authors.initials: I
authors.lastname: Nebie
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. vs.debe.cnrfp@fasonet.bf.
authors.forename: Débé
authors.initials: D
authors.lastname: Siaka
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. kjerstin.lanke@radboudumc.nl.
authors.forename: Kjerstin
authors.initials: K
authors.lastname: Lanke
authors.affiliation: Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK. chi.eziefula@googlemail.com.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Eziefula
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. a.diarra.cnrfp@fasonet.bf.
authors.forename: Amidou
authors.initials: A
authors.lastname: Diarra
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. helmi.pett@radboudumc.nl.
authors.forename: Helmi
authors.initials: H
authors.lastname: Pett
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. veddy.cnrfp@fasonet.bf.
authors.forename: Edith C
authors.initials: EC
authors.lastname: Bougouma
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. s.sirima.cnlp@fasonet.bf.
authors.forename: Sodiomon B
authors.initials: SB
authors.lastname: Sirima
authors.affiliation: Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK. chris.drakeley@lshtm.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. teun.bousema@radboudumc.nl.
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage*; D058345:Asymptomatic Infections; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D010963:Plasmodium falciparum; D015995:Prevalence; D011319:Primaquine / Q000008:administration & dosage*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D000077549:Artemether; D000078102:Lumefantrine; D011319:Primaquine