Targeting interventions to hotspots of malaria transmission is frequently mentioned as a cost-effective approach for malaria control and elimination
[2, 4, 5, 47], although direct evidence for a community effect of hotspot-targeted interventions is currently unavailable. The present study aims to determine this effect in a cluster-randomized intervention trial.
Valuable information on how to quantify community effects of malaria control interventions comes from trials with ITNs
. Mortality rates
, incidence of severe malaria
, incidence of uncomplicated malaria
[39, 50], anaemia
 and high-density parasitaemia
 have been shown to be reduced in compounds without ITNs that were in close proximity of compounds with ITNs. Hawley and colleagues found that individuals living in control villages within 300 m of ITN villages in Kenya experienced a level of protection similar to that experienced by individuals living in ITN villages and that this was plausibly due to area-wide effects on vector densities and sporozoite-positive mosquitoes
. Despite similarities, hotspot-targeted interventions may differ considerably from untargeted ITN campaigns in their community impact. Mathematical simulation models suggest that the impact of hotspot-targeted interventions may be much larger than that of community-wide ITN distributions and may lead to local malaria elimination
. In line with this, our trial is powered to detect large effects on malaria transmission. However, two of the major assumptions underlying the optimistic model outcomes are incompletely understood. Firstly, the stability of hotspots is central to ensure sustainable community effects. Hotspots of (asymptomatic) parasite carriage are generally assumed to be stable
[4, 10]. However, a report that wind direction in relation to breeding site location may be a key element in determining the location of hotspots
, suggests that local environmental factors may also influence the spatial stability of hotspots. We believe that our approach to define hotspots serologically may be less susceptible to (short-term) variations in wind direction or other ecological factors, since it effectively bases hotspot-detection on immunological markers of cumulative malaria exposure
. Secondly, a community effect of hotspot-targeted interventions strongly depends on mosquito mixing patterns. Mosquito mixing patterns are unlikely to be homogeneous. Reported site-fidelity where mosquitoes are likely to return to the same compounds
[51, 52] remains to be confirmed but could considerably reduce the community effect of hotspot-targeted interventions. The most informative measure of mixing patterns may be an approach where parasite populations are tracked in human populations, inside and outside hotspots of malaria transmission.
Research on the impact of community interventions where ‘herd coverage’ is required to ensure effectiveness raises a number of practical issues. Similar to mass drug administration campaigns, high community coverage
[53, 54] is required in our study to reduce R
0 to values below 1. Our intervention is further challenged by a dependence on community participation in control measures that are only rolled out in a selected proportion of this community. Gaining community trust is essential to the study’s success and we expect good participation rates after our lengthy sensitization process and strong involvement of community leaders and local workers in all aspects of the study preparation, intervention and evaluation.
Even with excellent participation rates, the nature of our intervention will remain susceptible to contamination from neighbouring hotspots. An ideal study setting would comprise a large number of geographically isolated clusters, each being an independent focus of malaria transmission, with clearly defined hotspots within these clusters
. Our real-life setting falls short of this ideal scenario. The continuous inhabitation in the area makes it unlikely that clusters are geographically isolated. We aim to minimize contamination from non-targeted malaria hotspots by incorporating an exclusion zone in our selection of eligible hotspots and in the selection of compounds in the evaluation phase. We nevertheless expect that there will be residual contamination that will be reflected in a spatial component in the effect of hotspot-targeted interventions: we expect the level of contamination to be highest in areas furthest away from the targeted hotspot and nearest to untargeted hotspots. Similarly, the effect of the intervention within the targeted hotspots may be largest in those compounds that are most remote from the nearest untargeted compound. Mathematical simulation models that incorporate heterogeneous malaria exposure
[16, 23, 38] are expected to be valuable as an integral part of the evaluation of our intervention to assess the plausibility that a change in transmission intensity can be attributed to the intervention.
The current study is not designed to determine the effect of individual interventions. While simulations suggest that targeted interventions with LLINs and IRS will be sufficient to eliminate malaria locally
, we chose a relatively comprehensive package of malaria control measures incorporating a wide variety of available interventions, targeting both the mosquito vector and the malaria parasite in humans. If findings from the current study prove promising, a next step will be to determine the optimum package of tools for hotspot-targeted interventions across a range of settings. This package will differ between different settings. Larviciding, for example, will be most beneficial in settings where breeding sites are discrete and well-defined
[55–57] while the effects of IRS and ITNs will be affected by insecticide resistance, amongst other factors
. Importantly, follow-up studies should determine the cost-effectiveness of the hotspot approach to assess whether savings in the number of compounds that need to be targeted for conventional vector control in the absence of hotspot treatment outweigh the costs for hotspot-detection and coordination of hotspot interventions.