title: A cluster-randomized trial of mass drug administration with a gametocytocidal drug combination to interrupt malaria transmission in a low endemic area in Tanzania.
abstract: BACKGROUND
  Effective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission. The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission, the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention. The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine (SP) plus artesunate (AS) plus primaquine (PQ, single dose 0.75 mg/kg) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania.
  
  
  METHODS
  In a cluster-randomized trial in four villages in Lower Moshi, Tanzania, eight clusters (1,110 individuals; cluster size 47- 209) were randomized to observed treatment with SP+AS+PQ and eight clusters (2,347 individuals, cluster size 55- 737) to treatment with placebo over three days. Intervention and control clusters were 1 km apart; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation. Passive case detection was done for the entire cohort and active case detection in 149 children aged 1-10 year from the intervention arm and 143 from the control arm. Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period.
  
  
  RESULTS
  The coverage rate in the intervention arm was 93.0% (1,117/1,201). Parasite prevalence by molecular detection methods was 2.2-2.7% prior to the intervention and undetectable during follow-up in both the control and intervention clusters. None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities. Three clinical malaria episodes occurred in the intervention (n = 1) and control clusters (n = 2).
  
  
  CONCLUSIONS
  This study illustrates the possibility to achieve high coverage with a three-day intervention but also the difficulty in defining suitable outcome measures to evaluate interventions in areas of very low malaria transmission intensity. The decline in transmission intensity prior to the intervention made it impossible to assess the impact of MDA in the chosen study setting.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00509015.
authors.affiliation: Kilimanjaro Christian Medical College-Kilimanjaro Clinical Research Institute, Moshi, Tanzania. sshekalaghe@yahoo.com
authors.forename: Seif A
authors.initials: SA
authors.lastname: Shekalaghe
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.forename: Sven
authors.initials: S
authors.lastname: van den Bosch
authors.forename: Roel
authors.initials: R
authors.lastname: ter Braak
authors.forename: Wouter
authors.initials: W
authors.lastname: van den Bijllaardt
authors.forename: Charles
authors.initials: C
authors.lastname: Mwanziva
authors.forename: Salimu
authors.initials: S
authors.lastname: Semvua
authors.forename: Alutu
authors.initials: A
authors.lastname: Masokoto
authors.forename: Frank
authors.initials: F
authors.lastname: Mosha
authors.forename: Karina
authors.initials: K
authors.lastname: Teelen
authors.forename: Rob
authors.initials: R
authors.lastname: Hermsen
authors.forename: Lucy
authors.initials: L
authors.lastname: Okell
authors.forename: Roly
authors.initials: R
authors.lastname: Gosling
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000379:methods; D019353:Endemic Diseases / Q000517:prevention & control; D005260:Female; D006801:Humans; D007223:Infant; D008288:Malaria / Q000517:prevention & control* / Q000635:transmission*; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D018512:Parasitemia / Q000175:diagnosis; D010919:Placebos / Q000008:administration & dosage; D011319:Primaquine / Q000008:administration & dosage; D011739:Pyrimethamine / Q000008:administration & dosage; D013413:Sulfadoxine / Q000008:administration & dosage; D013636:Tanzania / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D010919:Placebos; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011319:Primaquine; D011739:Pyrimethamine