title: Sickle cell trait is associated with a delayed onset of malaria: implications for time-to-event analysis in clinical studies of malaria.
abstract: BACKGROUND
  The World Health Organization (WHO) recently recommended that the time to first malaria episode serve as the primary end point in phase III malaria vaccine trials--the first of which will be held in Africa. Although common red blood cell (RBC) polymorphisms such as sickle hemoglobin (HbS) are known to protect against malaria in Africa, their impact on this end point has not been investigated.
  
  
  METHODS
  A longitudinal study of 225 individuals aged 2-25 years was conducted in Mali. The association between common RBC polymorphisms and the time to first malaria episode was evaluated.
  
  
  RESULTS
  Among children aged 2-10 years, sickle cell trait (HbAS) was associated with a 34-day delay in the median time to first malaria episode (P= .017) Cox regression analysis showed that greater age (hazard ratio [HR], 0.87 [95% CI, 0.80-0.94]; (P= .001), HbAS (HR, 0.48 [95% CI, 0.26-0.91]; (P= .024), and asymptomatic parasitemia at enrollment (HR, 0.35 [95% CI, 0.14-0.85]; (P= .021) were associated with decreased malaria risk.
  
  
  CONCLUSIONS
  Given the delay in the time to first malaria episode associated with HbAS, it would be advisable for clinical trials and observational studies that use this end point to include Hb typing in the design of studies conducted in areas where HbAS is prevalent.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA. pcrompton@niaid.nih.gov
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traore
authors.forename: Kassoum
authors.initials: K
authors.lastname: Kayentao
authors.forename: Safiatou
authors.initials: S
authors.lastname: Doumbo
authors.forename: Aissata
authors.initials: A
authors.lastname: Ongoiba
authors.forename: Seidina A S
authors.initials: SA
authors.lastname: Diakite
authors.forename: Michael A
authors.initials: MA
authors.lastname: Krause
authors.forename: Didier
authors.initials: D
authors.lastname: Doumtabe
authors.forename: Younoussou
authors.initials: Y
authors.lastname: Kone
authors.forename: Greta
authors.initials: G
authors.lastname: Weiss
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Seydou
authors.initials: S
authors.lastname: Doumbia
authors.forename: Aldiouma
authors.initials: A
authors.lastname: Guindo
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Susan K
authors.initials: SK
authors.lastname: Pierce
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo