Spatiotemporal effects on dengue incidence based on a large cluster randomized study

A recent large-scale cluster randomized test-negative study assessed the impact of a mosquito-based intervention on the incidence of clinical dengue showing a protective efficacy of 77.1% (95% CI: (65.3%, 84.9%)). While the intervention was randomized at a cluster-level, human and mosquito movement suggest potential violations in assumptions necessary for intention-to-treat analyses to produce accurate estimates of the full intervention effect due to spatial clustering of dengue cases, and/or potential non-independence in the intervention arising from spillover of the intervention (or control) across cluster boundaries. We address these distinct but related effects using two approaches. First, we examine whether a clustering effect exists, that is, whether the presence of a recent dengue case in the sample within a specified distance from a residence raises the risk of dengue. Second, we use cluster reallocation techniques to examine intervention spillover effects. We find strong spatial effects of the presence of dengue cases on the risk of clinical dengue that exhibit both serospecificity and a dose response, more evident in control than intervention clusters at least on an additive scale. Contrarily, there is no evidence of any appreciable local spillover effect from intervention to control clusters, or vice versa, in terms of either the risk of dengue infection or the level of disease clustering.