title: Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Shoklo SPf66 Malaria Vaccine Trial Group.
abstract: BACKGROUND
  Previous efficacy trials of SPf66 malaria vaccine have produced conflicting results in different populations. We report a randomised double-blind trial of the SPf66 vaccine conducted in Karen children aged 2-15 living in a malarious region of northwestern Thailand. Recombinant hepatitis B vaccine was used as a comparator.
  
  
  METHODS
  The study had a power of 90% to detect an efficacy of 30%, defined as a reduction in the incidence of first cases of symptomatic falciparum malaria after three doses of vaccine. 1221 children received three immunisations and were eligible for the primary efficacy analysis. Intense active and passive case detection continued over 15 months of follow-up.
  
  
  RESULTS
  The SPf66 vaccine was well tolerated, although 26 children had mild or moderately severe local or systemic allergic reactions, compared with none in the comparator group. The vaccine was immunogenic; after three doses, 73% of recipients had seroconverted. There were no deaths due to malaria during the study. During the 15-month period of evaluation there were 379 first cases of symptomatic falciparum malaria (195 in the SPf66 recipients, 184 in the comparator group); an SPf66 efficacy of -9% (95% CI -33 to 14, p = 0.41). No significant differences between the two study groups in parasite density or any other measure of malaria-related morbidity were detected.
  
  
  CONCLUSIONS
  These findings are consistent with a recent study showing lack of efficacy of SPf66 among Gambian infants and differ from earlier positive reports from South America and evidence of borderline efficacy from Tanzania. We conclude that SPf66 does not protect against clinical falciparum malaria and that further efficacy trials are not warranted.
authors.affiliation: Shoklo Malaria Research Unit, Mae Sot, Thailand.
authors.forename: F
authors.initials: F
authors.lastname: Nosten
authors.forename: C
authors.initials: C
authors.lastname: Luxemburger
authors.forename: D E
authors.initials: DE
authors.lastname: Kyle
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
authors.forename: J
authors.initials: J
authors.lastname: Wittes
authors.forename: E
authors.initials: E
authors.lastname: Wah
authors.forename: T
authors.initials: T
authors.lastname: Chongsuphajaisiddhi
authors.forename: D M
authors.initials: DM
authors.lastname: Gordon
authors.forename: N J
authors.initials: NJ
authors.lastname: White
authors.forename: J C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: D G
authors.initials: DG
authors.lastname: Heppner
mesh_terms: D000293:Adolescent; D000818:Animals; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology; D015994:Incidence; D016015:Logistic Models; D008288:Malaria / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008297:Male; D016017:Odds Ratio; D010963:Plasmodium falciparum / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000276:immunology; D011537:Pruritus / Q000139:chemically induced; D011994:Recombinant Proteins; D012306:Risk; D016019:Survival Analysis; D015996:Survival Rate; D013785:Thailand / Q000453:epidemiology
chemical_list: D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C066269:SPf66 protein, Plasmodium