title: Efficacy and safety of the mosquitocidal drug ivermectin to prevent malaria transmission after treatment: a double-blind, randomized, clinical trial.
abstract: BACKGROUND
  Artemisinin combination therapy effectively clears asexual malaria parasites and immature gametocytes but does not prevent posttreatment malaria transmission. Ivermectin (IVM) may reduce malaria transmission by killing mosquitoes that take blood meals from IVM-treated humans.
  
  
  METHODS
  In this double-blind, placebo-controlled trial, 120 asymptomatic Plasmodium falciparum parasite carriers were randomized to receive artemether-lumefantrine (AL) plus placebo or AL plus a single or repeated dose (200 µg/kg) of ivermectin (AL-IVM1 and AL-IVM2, respectively). Mosquito membrane feeding was performed 1, 3, and 7 days after initiation of treatment to determine Anopheles gambiae and Anopheles funestus survival and infection rates.
  
  
  RESULTS
  The AL-IVM combination was well tolerated. IVM resulted in a 4- to 7-fold increased mortality in mosquitoes feeding 1 day after IVM (P < .001). Day 7 IVM plasma levels were positively associated with body mass index (r = 0.57, P < .001) and were higher in female participants (P = .003), for whom An. gambiae mosquito mortality was increased until 7 days after a single dose of IVM (hazard rate ratio, 1.34 [95% confidence interval, 1.07-1.69]; P = .012). Although we found no evidence that IVM reduced Plasmodium infection rates among surviving mosquitoes, the mosquitocidal effect of AL-IVM1 and AL-IVM2 resulted in 27% and 35% reductions, respectively, in estimated malaria transmission potential during the first week after initiation of treatment.
  
  
  CONCLUSIONS
  We conclude that IVM can be safely given in combination with AL and can reduce the likelihood of malaria transmission by reducing the life span of feeding mosquitoes.
  
  
  BACKGROUND
  NCT0160325.
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: André Lin
authors.initials: AL
authors.lastname: Ouédraogo
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Guido J H
authors.initials: GJ
authors.lastname: Bastiaens
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
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.
authors.forename: Wamdaogo M
authors.initials: WM
authors.lastname: Guelbéogo
authors.affiliation: Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland Entomology Department, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kobylinski
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
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.
authors.forename: Aïssata
authors.initials: A
authors.lastname: Barry
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
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.
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.
authors.forename: Maurice San
authors.initials: MS
authors.lastname: Ouattara
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Kjerstin H W
authors.initials: KH
authors.lastname: Lanke
authors.affiliation: College of Pharmacy, The University of Iowa, Iowa City.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fleckenstein
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Infectious Disease Epidemiology, Imperial College London.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Slater
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Infectious Disease Epidemiology, Imperial College London.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Churcher
authors.affiliation: Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors.forename: Sodiomon B
authors.initials: SB
authors.lastname: Sirima
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use; D009033:Culicidae; D004311:Double-Blind Method; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D006801:Humans; D007306:Insecticides / Q000627:therapeutic use*; D007559:Ivermectin / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission*; D008297:Male
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D007306:Insecticides; D007559:Ivermectin
keywords: falciparum; gametocyte; sporogony; survivorship; transmission