title: A cluster-randomized controlled trial to assess the effectiveness of using 15% DEET topical repellent with long-lasting insecticidal nets (LLINs) compared to a placebo lotion on malaria transmission.
abstract: BACKGROUND
  Long-lasting insecticidal nets (LLINs) have limited effect on malaria transmitted outside of sleeping hours. Topical repellents have demonstrated reduction in the incidence of malaria transmitted in the early evening. This study assessed whether 15% DEET topical repellent used in combination with LLINs can prevent greater malaria transmission than placebo and LLINs, in rural Tanzania.
  
  
  METHODS
  A cluster-randomized, placebo-controlled trial was conducted between July 2009 and August 2010 in a rural Tanzanian village. Sample size calculation determined that 10 clusters of 47 households with five people/household were needed to observe a 24% treatment effect at the two-tailed 5% significance level, with 90% power, assuming a baseline malaria incidence of one case/person/year. Ten clusters each were randomly assigned to repellent and control groups by lottery. A total of 4,426 individuals older than six months were enrolled. All households in the village were provided with an LLIN per sleeping space. Repellent and placebo lotion was replaced monthly. The main outcome was rapid diagnostic test (RDT)-confirmed malaria measured by passive case detection (PCD). Incidence rate ratios were estimated from a Poisson model, with adjustment for potential confounders, determined a priori. According-to-protocol approach was used for all primary analyses.
  
  
  RESULTS
  The placebo group comprised 1972.3 person-years with 68.29 (95% C.I 37.05-99.53) malaria cases/1,000 person-years. The repellent group comprised 1,952.8 person-years with 60.45 (95% C.I 48.30-72.60) cases/1,000 person-years, demonstrating a non-significant 11.44% reduction in malaria incidence rate in this group, (Wilcoxon rank sum z=0.529, p=0.596). Principal components analysis (PCA) of the socio-economic status (SES) of the two groups demonstrated that the control group had a higher SES (Pearson's chi square=13.38, p=0.004).
  
  
  CONCLUSIONS
  Lack of an intervention effect was likely a result of lack of statistical power, poor capture of malaria events or bias caused by imbalance in the SES of the two groups. Low malaria transmission during the study period could have masked the intervention effect and a larger study size was needed to increase discriminatory power. Alternatively, topical repellents may have no impact on malaria transmission in this scenario. Design and implementation of repellent intervention studies is discussed.
  
  
  BACKGROUND
  The trial was registered ISRCTN92202008--http://www.controlled-trials.com/ISRCTN92202008.
authors.affiliation: Ifakara Health Institute, Box 74, Bagamoyo, Tanzania. psangoro@ihi.or.tz.
authors.forename: Onyango
authors.initials: O
authors.lastname: Sangoro
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Turner
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Simfukwe
authors.forename: Jane E
authors.initials: JE
authors.lastname: Miller
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003671:DEET / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007302:Insect Repellents / Q000008:administration & dosage / Q000627:therapeutic use*; D057148:Insecticide-Treated Bednets; D057194:Intention to Treat Analysis; D008288:Malaria / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D009032:Mosquito Control / Q000379:methods*; D010349:Patient Compliance; D010919:Placebos / Q000008:administration & dosage / Q000627:therapeutic use*; D063465:Skin Cream / Q000008:administration & dosage / Q000627:therapeutic use*; D012959:Socioeconomic Factors; D013636:Tanzania / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007302:Insect Repellents; D010919:Placebos; D003671:DEET