title: Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate.
abstract: BACKGROUND
  P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. We determined the efficacy of SP+AS plus a single dose of primaquine (PQ, 0.75 mg/kg) on clearing gametocytaemia measured by molecular methods.
  
  
  METHODS
  The study was conducted in Mnyuzi, an area of hyperendemic malaria in north-eastern Tanzania. Children aged 3-15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500-100,000 parasites/microL were randomized to receive treatment with either SP+AS or SP+AS+PQ. P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification (QT-NASBA). Haemoglobin levels (Hb) were determined to address concerns about haemolysis in G6PD-deficient individuals.
  
  
  RESULTS
  108 individuals were randomized. Pfs25 QT-NASBA gametocyte prevalence was 88-91% at enrolment and decreased afterwards for both treatment arms. Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ. On day 14 after treatment 3.9% (2/51) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7% (32/51) of those treated with SP+AS (p<0.001). Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency. The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment.
  
  
  CONCLUSIONS
  PQ clears submicroscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission. For individuals without severe anaemia, addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment.
  
  
  BACKGROUND
  Controlled-Trials.com ISRCTN61534963.
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Seif
authors.initials: S
authors.lastname: Shekalaghe
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.forename: Roly
authors.initials: R
authors.lastname: Gosling
authors.forename: Arnold
authors.initials: A
authors.lastname: Ndaro
authors.forename: Monique
authors.initials: M
authors.lastname: van Meegeren
authors.forename: Anders
authors.initials: A
authors.lastname: Enevold
authors.forename: Michael
authors.initials: M
authors.lastname: Alifrangis
authors.forename: Frank
authors.initials: F
authors.lastname: Mosha
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
mesh_terms: D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000378:metabolism*; D011319:Primaquine / Q000627:therapeutic use*; D011739:Pyrimethamine / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013636:Tanzania; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011319:Primaquine; D011739:Pyrimethamine