Dataset Information

Calibration of an intrahost malaria model and parameter ensemble evaluation of a pre-erythrocytic vaccine.

ABSTRACT:

Background

A pre-erythrocytic vaccine could provide a useful tool for burden reduction and eventual eradication of malaria. Mathematical malaria models provide a mechanism for evaluating the effective burden reduction across a range of transmission conditions where such a vaccine might be deployed.

Methods

The EMOD model is an individual-based model of malaria transmission dynamics, including vector lifecycles and species-specific behaviour, coupled to a mechanistic intrahost model of malaria parasite and host immune system dynamics. The present work describes the extension of the EMOD model to include diagnoses of severe malaria and iterative calibration of the immune system parameters and parasite antigenic variation to age-stratified prevalence, incidence and severe disease incidence data obtained from multiple regions with broadly varying transmission conditions in Africa. An ensemble of calibrated model parameter sets is then employed to evaluate the potential impact of routine immunization with a pre-erythrocytic vaccine.

Results

The reduction in severe malaria burden exhibits a broad peak at moderate transmission conditions. Under sufficiently intense transmission, a vaccine that reduces but does not eliminate the probability of acquisition from a single challenge bite may delay infections but produces minimal or no net reduction. Conversely, under sufficiently weak transmission conditions, a vaccine can provide a high fractional reduction but avert a relatively low absolute number of cases due to low baseline burden.

Conclusions

Roll-out of routine immunization with pre-erythrocytic malaria vaccines can provide substantial burden reduction across a range of transmission conditions typical to many regions in Africa.

SUBMITTER: McCarthy KA

PROVIDER: S-EPMC4326442 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Publications

Calibration of an intrahost malaria model and parameter ensemble evaluation of a pre-erythrocytic vaccine.

McCarthy Kevin A KA Wenger Edward A EA Huynh Grace H GH Eckhoff Philip A PA

Malaria journal 20150107

<h4>Background</h4>A pre-erythrocytic vaccine could provide a useful tool for burden reduction and eventual eradication of malaria. Mathematical malaria models provide a mechanism for evaluating the effective burden reduction across a range of transmission conditions where such a vaccine might be deployed.<h4>Methods</h4>The EMOD model is an individual-based model of malaria transmission dynamics, including vector lifecycles and species-specific behaviour, coupled to a mechanistic intrahost mode ...[more]

PMID: 25563798

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Project description:BackgroundThe 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.Methods and findingsAn 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.ConclusionsIn 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.

Dataset Information

Calibration of an intrahost malaria model and parameter ensemble evaluation of a pre-erythrocytic vaccine.

Background

Methods

Results

Conclusions

Publications

Calibration of an intrahost malaria model and parameter ensemble evaluation of a pre-erythrocytic vaccine.

Similar Datasets

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