title: Potential public health impact of RTS,S malaria candidate vaccine in sub-Saharan Africa: a modelling study.
abstract: BACKGROUND
  Adding malaria vaccination to existing interventions could help to reduce the health burden due to malaria. This study modelled the potential public health impact of the RTS,S candidate malaria vaccine in 42 malaria-endemic countries in sub-Saharan Africa.
  
  
  METHODS
  An individual-based Markov cohort model was constructed with three categories of malaria transmission intensity and six successive malaria immunity levels. The cycle time was 5 days. Vaccination was assumed to reduce the risk of infection, with no other effects. Vaccine efficacy was assumed to wane exponentially over time. Malaria incidence and vaccine efficacy data were taken from a Phase III trial of the RTS,S vaccine with 18 months of follow-up (NCT00866619). The model was calibrated to reproduce the malaria incidence in the control arm of the trial in each transmission category and published age distribution data. Individual-level heterogeneity in malaria exposure and vaccine protection was accounted for. Parameter uncertainty and variability were captured by using stochastic model transitions. The model followed a cohort from birth to 10 years of age without malaria vaccination, or with RTS,S malaria vaccination administered at age 6, 10 and 14 weeks or at age 6, 7-and-a-half and 9 months. Median and 95% confidence intervals were calculated for the number of clinical malaria cases, severe cases, malaria hospitalizations and malaria deaths expected to be averted by each vaccination strategy. Univariate sensitivity analysis was conducted by varying the values of key input parameters.
  
  
  RESULTS
  Vaccination assuming the coverage of diphtheria-tetanus-pertussis (DTP3) at age 6, 10 and 14 weeks is estimated to avert over five million clinical malaria cases, 119,000 severe malaria cases, 98,600 malaria hospitalizations and 31,000 malaria deaths in the 42 countries over the 10-year period. Vaccination at age 6, 7-and-a-half and 9 months with 75% of DTP3 coverage is estimated to avert almost 12.5 million clinical malaria cases, 250,000 severe malaria cases, 208,000 malaria hospitalizations and 65,400 malaria deaths in the 42 countries. Univariate sensitivity analysis indicated that for both vaccination strategies, the parameters with the largest impact on the malaria mortality estimates were waning of vaccine efficacy and malaria case-fatality rate.
  
  
  CONCLUSIONS
  Addition of RTS,S malaria vaccination to existing malaria interventions is estimated to reduce substantially the incidence of clinical malaria, severe malaria, malaria hospitalizations and malaria deaths across 42 countries in sub-Saharan Africa.
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300, Wavre, Belgium. christophe.j.sauboin@gsk.com.
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: Sauboin
authors.affiliation: CHESS in Health, Zwarte Leeuwstraat 69, 2820, Bonheiden, Belgium. lvanbellinghen@chessinhealth.com.
authors.forename: Laure-Anne
authors.initials: LA
authors.lastname: Van Bellinghen
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300, Wavre, Belgium. nicolas.x.van-de-velde@gsk.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Van De Velde
authors.affiliation: CHESS in Health, Zwarte Leeuwstraat 69, 2820, Bonheiden, Belgium. ivanvlaenderen@chessinhealth.com.
authors.forename: Ilse
authors.initials: I
authors.lastname: Van Vlaenderen
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000517:prevention & control*; D008390:Markov Chains; D015233:Models, Statistical; D011634:Public Health / Q000706:statistics & numerical data*
chemical_list: D017780:Malaria Vaccines