Abstract
BackgroundA 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.MethodsThe 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.ResultsThe 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.ConclusionsRoll-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.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-14-6) contains supplementary material, which is available to authorized users.
Highlights
A pre-erythrocytic vaccine could provide a useful tool for burden reduction and eventual eradication of malaria
Over essentially the entire range of simulated transmission conditions, the model predicts that a pre-erythrocytic vaccine delivered early in life results in a reduction in the rate of severe malarial incidence for some period of time, followed by a rebound in case counts, when the delayed onset of acquired immunity results in vaccinated children exhibiting a higher rate of severe malaria incidence than unvaccinated children
The relative magnitudes and timescales of case reduction and rebound are most strongly dependent on the magnitude of the Entomological inoculation rate (EIR) and the vaccine profile, and less so on the model input parameters or the seasonality
Summary
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. Improvements in vector control, diagnostics and treatment have all contributed to the declining mortality [2,3,4], and a preventative vaccine could provide an important additional tool to the malaria control and eradication effort. Mathematical models of malaria transmission and within-host disease progression can aid in understanding the effects of potential vaccine distributions under a broad range of transmission conditions. A variety of potential vaccines are under investigation; depending on which stage of the parasite lifecycle is targeted, a vaccine could act to prevent human acquisition, reduce morbidity post-acquisition, or prevent transmission from human hosts back to the mosquito vectors. Campaign interventions targeting the vector population (insecticide-treated nets, habitat clearance) or the human population (vaccines, anti-malarial drug regimens, etc.) can be flexibly distributed to specified subpopulations, e.g., age-based immunization schedules, calendarbased distribution campaigns or treatment-seeking upon onset of symptoms
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