Ensemble Modeling of the Likely Public Health Impact of a Pre-Erythrocytic Malaria Vaccine
Open Access
- 17 January 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Medicine
- Vol. 9 (1), e1001157
- https://doi.org/10.1371/journal.pmed.1001157
Abstract
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. 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. 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. Please see later in the article for the Editors' SummaryThis publication has 55 references indexed in Scilit:
- Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trialThe Lancet Infectious Diseases, 2011
- Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5–17 months in Kenya and Tanzania: a randomised controlled trialThe Lancet Infectious Diseases, 2011
- Immunological mechanisms underlying protection mediated by RTS,S: a review of the available dataMalaria Journal, 2009
- A Bayesian approach to uncertainty analysis of sexually transmitted infection modelsSexually Transmitted Infections, 2009
- Long‐Term Safety and Efficacy of the RTS,S/AS02A Malaria Vaccine in Mozambican ChildrenThe Journal of Infectious Diseases, 2009
- Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in InfantsThe New England Journal of Medicine, 2008
- Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of AgeThe New England Journal of Medicine, 2008
- Spatial effects of mosquito bednets on child mortalityBMC Public Health, 2008
- Progress and challenges in modelling country-level HIV/AIDS epidemics: the UNAIDS Estimation and Projection Package 2007Sexually Transmitted Infections, 2008
- Modeling targeted layered containment of an influenza pandemic in the United StatesProceedings of the National Academy of Sciences of the United States of America, 2008