title: Ensemble modeling of the likely public health impact of a pre-erythrocytic malaria vaccine.
abstract: BACKGROUND
  The RTS,S malaria vaccine may soon be licensed. Models of impact of such vaccines have mainly considered deployment via the World Health Organization's Expanded Programme on Immunization (EPI) in areas of stable endemic transmission of Plasmodium falciparum, and have been calibrated for such settings. Their applicability to low transmission settings is unclear. Evaluations of the efficiency of different deployment strategies in diverse settings should consider uncertainties in model structure.
  
  
  RESULTS
  An ensemble of 14 individual-based stochastic simulation models of P. falciparum dynamics, with differing assumptions about immune decay, transmission heterogeneity, and treatment access, was constructed. After fitting to an extensive library of field data, each model was used to predict the likely health benefits of RTS,S deployment, via EPI (with or without catch-up vaccinations), supplementary vaccination of school-age children, or mass vaccination every 5 y. Settings with seasonally varying transmission, with overall pre-intervention entomological inoculation rates (EIRs) of two, 11, and 20 infectious bites per person per annum, were considered. Predicted benefits of EPI vaccination programs over the simulated 14-y time horizon were dependent on duration of protection. Nevertheless, EPI strategies (with an initial catch-up phase) averted the most deaths per dose at the higher EIRs, although model uncertainty increased with EIR. At two infectious bites per person per annum, mass vaccination strategies substantially reduced transmission, leading to much greater health effects per dose, even at modest coverage.
  
  
  CONCLUSIONS
  In higher transmission settings, EPI strategies will be most efficient, but vaccination additional to the EPI in targeted low transmission settings, even at modest coverage, might be more efficient than national-level vaccination of infants. The feasibility and economics of mass vaccination, and the circumstances under which vaccination will avert epidemics, remain unclear. The approach of using an ensemble of models provides more secure conclusions than a single-model approach, and suggests greater confidence in predictions of health effects for lower transmission settings than for higher ones.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland. Thomas-A.Smith@unibas.ch
authors.forename: Thomas
authors.initials: T
authors.lastname: Smith
authors.forename: Amanda
authors.initials: A
authors.lastname: Ross
authors.forename: Nicolas
authors.initials: N
authors.lastname: Maire
authors.forename: Nakul
authors.initials: N
authors.lastname: Chitnis
authors.forename: Alain
authors.initials: A
authors.lastname: Studer
authors.forename: Diggory
authors.initials: D
authors.lastname: Hardy
authors.forename: Alan
authors.initials: A
authors.lastname: Brooks
authors.forename: Melissa
authors.initials: M
authors.lastname: Penny
authors.forename: Marcel
authors.initials: M
authors.lastname: Tanner
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D004912:Erythrocytes / Q000469:parasitology*; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D015994:Incidence; D007223:Infant; D008018:Life Cycle Stages; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000401:mortality / Q000469:parasitology / Q000517:prevention & control* / Q000635:transmission; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology*; D015995:Prevalence; D011634:Public Health; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D017780:Malaria Vaccines