Abstract
BackgroundWith the encouraging advent of new malaria vaccine candidates, mathematical modelling of expected impacts of present and future vaccines as part of multi-intervention strategies is especially relevant.MethodsThe impact of potential malaria vaccines is presented utilizing the EMOD model, a comprehensive model of the vector life cycle coupled to a detailed mechanistic representation of intra-host parasite and immune dynamics. Values of baseline transmission and vector feeding behaviour parameters are identified, for which local elimination is enabled by layering pre-erythrocytic vaccines of various efficacies on top of high and sustained insecticide-treated net coverage. The expected reduction in clinical cases is further explored in a scenario that targets children by adding a pre-erythrocytic vaccine to the EPI programme for newborns.ResultsAt high transmission, there is a minimal reduction in clinical disease cases, as the time to infection is only slightly delayed. At lower transmission, there is an accelerating community-level protection that has subtle dependences on heterogeneities in vector behaviour, ecology, and intervention coverage. At very low transmission, the trend reverses as many children are vaccinated to prevent few cases.ConclusionsThe maximum-impact setting is one in which the impact of increasing bed net coverage has saturated, vector feeding is primarily outdoors, and transmission is just above the threshold where small perturbations from a vaccine intervention result in large community benefits.
Highlights
With the encouraging advent of new malaria vaccine candidates, mathematical modelling of expected impacts of present and future vaccines as part of multi-intervention strategies is especially relevant
In recent years, dramatic progress has been made in reducing the burden of malaria through the scale-up of insecticide-treated net (ITN) coverage and the increasing use of artemisinin combination therapy (ACT) as first-line treatment [1,2,3,4]
The present study utilizes the Disease Transmission Kernel (DTK) model developed by the Epidemiological Modelling (EMOD) group at Intellectual Ventures
Summary
With the encouraging advent of new malaria vaccine candidates, mathematical modelling of expected impacts of present and future vaccines as part of multi-intervention strategies is especially relevant. In Phase IIb and Phase III field trials to date, the following protective efficacies have been observed: 34% against infection in Gambian adults waning rapidly over 15 weeks [14]; 30% against clinical episodes and 45% against infection in Mozambican children over 6 months [15] and persisting at similar levels out to 21 months [16]; 49–56% against clinical episodes over a year in children from Kenyan and Tanzanian children [17] and from seven African countries [18,19] These trials are consistent with a ‘leaky’ vaccine that provides partial protection to most vaccinated individuals [20,21] by reducing the number of successful sporozoites and the size of the liver-to-blood inoculum [22]. Recent Phase I trials targeting the sexual stage of the parasite, in particular the ookinete surface proteins Pfs and Pfs, have demonstrated persistent high antibody levels that are effective in blocking oocyst formation in the mosquito [23,24,25,26]
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