Interventions using current tools can result in major reductions in malaria transmission and the associated disease burden; however, in high transmission settings they are insufficient to drive prevalence below the pre-elimination threshold [
50]. A malaria vaccine offers, therefore, great potential for improved malaria control, particularly in Africa, where effective mosquito control over long periods has proved difficult or impossible to maintain [
51]. Indeed recent successes in malaria control using other approaches highlight the need and the potential gains that could come from an efficacious vaccine [
8,
10]. However, to adequately measure vaccine impact will require enhanced surveillance and standardized reporting mechanisms. Unfortunately, the large range of R
0 estimates in literature confirms the fact that malaria control presents variable challenges across its transmission spectrum and a ‘‘one-size-fits-all’’ malaria control strategy would be inefficient in the broader context of malaria elimination [
16]. Large reductions in transmission from targeted control are possible only if programmes are able to identify those who are bitten most, and specific interventions packaged and implemented efficiently. Vector control measures can impact reductions to the 1% parasite prevalence threshold in low- to moderate-transmission settings especially when the main vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention programme is efficiently managed. In high-transmission settings and areas, where vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required [
50,
52,
53]. Depending on which stage (see Figure
3) in control a particular region might be at, specific tailor-made interventions would be required to move from one stage to the next. In areas where R
0 is low such as those around stage 3, local elimination of malaria may be practical and concerted efforts should focus on that goal [
52]. The immediate realistic focus of control should be reducing the mortality and disease burden in general, for areas where R
0 may be high such as those around stage 1 and 2.
On the other hand, the impact of the malaria interventions should not be limited to the estimated level of efficacy and coverage alone. The potential impact of vaccines could generally be wider than expected due to synergies and doubling of effects, which is hard to theoretically predict. For example, RTS,S was observed to have an impressive reduction in severe disease incidence in Mozambican children despite being a pre-erythrocytic stage vaccine [
54]. This trial was designed to primarily assess vaccine efficacy against clinical malaria disease, which at six months was found be 29·9% (95% CI 11·0–44·8; p 0·004) while efficacy against severe malaria was 57·7% (95% CI 16·2–80·6; p 0·019). Could synergies between a partially protective malaria vaccine and currently available control tools further enhance the impact of vaccine?