Spatial spillover analysis of a cluster-randomized trial against dengue vectors in Trujillo, Venezuela

Background: The ability of cluster-randomized trials to capture mass or indirect effects is one reason for their increasing use to test interventions against vector-borne diseases such as malaria and dengue. For the same reason, however, the independence of clusters may be compromised if the distances between clusters is too small to ensure independence. In other words they may be subject to spillover effects. Methods: We distinguish two types of spatial spillover effect: between-cluster dependence in outcomes, or spillover dependence; and modification of the intervention effect according to distance to the intervention arm, or spillover indirect effect. We estimate these effects in trial of insecticide-treated materials against the dengue mosquito vector, Aedes aegypti, in Venezuela, the endpoint being the Breteau index. We use a novel random effects Poisson spatial regression model. Spillover dependence is incorporated via an orthogonalized intrinsic conditional autoregression (ICAR) model. Spillover indirect effects are incorporated via the number of locations within a certain radius, set at 200m, that are in the intervention arm. Results: From the model with ICAR spatial dependence, and the degree of surroundedness, the intervention effect is estimated as 0.74—favouring the intervention—with a 95% credible interval of 0.34 to 1.69. The point estimates are stronger with increasing surroundedness within intervention locations. Conclusion: In this trial there is some evidence of a spillover indirect effect of the intervention, with the Breteau index tending to be lower in locations which are more surrounded by locations in the intervention arm. Author summary: Control methods for dengue, and other diseases which are transmitted by mosquitoes, are often tested in cluster-randomized trials. This means that whole groups of people, often defined by geographical area, are randomly allocated to receive the control method or not. These control methods often have a mass effect so that they may be stronger if applied to a whole area together. However, if the areas (clusters) are not very far apart then the effects may ‘spill over’ from one to another. In this paper we use a new spatial statistical method to re-analyse data from a cluster-randomized trial which was done in a town in Venezuela. The idea was to use insecticide treated curtains and water tank covers to try to control the mosquitoes which transmit dengue. To assess the spillover effect we calculate how much each location was surrounded by locations which got the control method. We found some evidence that the greater the surroundedness then the stronger the effect of the intervention.