BACKGROUND: The RTS,S @entity311 vaccine may soon be licensed. Models of impact of such vaccines have mainly considered deployment via the World Health Organization's @entity1200 ( @entity1200 ) in areas of stable endemic transmission of @entity3964 , 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. METHODS AND FINDINGS: An ensemble of 14 individual-based stochastic simulation models of @entity3964 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 @entity1200 (with or without catch-up vaccinations), supplementary vaccination of school-age @entity1 , 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 @entity1 per annum, were considered. Predicted benefits of @entity1200 vaccination programs over the simulated 14-y time horizon were dependent on duration of protection. Nevertheless, @entity1200 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 @entity1 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, @entity1200 strategies will be most efficient, but vaccination additional to the @entity1200 in targeted low transmission settings, even at modest coverage, might be more efficient than national-level vaccination of @entity1 . 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.

Ensemble modeling of the likely public health impact of a pre-erythrocytic XXXX vaccine.

@entity1 :: ('9606', 'Species') :: ['children', 'infants', 'person'] @entity311 :: ('MESH:D008288', 'Disease') :: ['malaria'] @entity1200 :: ('MESH:D007154', 'Disease') :: ['Expanded Programme on Immunization', 'EPI'] @entity3964 :: ('5833', 'Species') :: ['P. falciparum', 'Plasmodium falciparum']
@entity311 :: (MESH:D008288,Disease) :: ['malaria']
