Heterogeneous suppressive effect of Wolbachia incompatible insect technique coupled with sterile insect technique across time and historical Ae. aegypti abundance - using distributional synthetic controls

Background: Biological control tools such as Wolbachia incompatible-insect technique, are a promising class of interventions to modify and suppress Aedes aegypti mosquitoes to reduce risk of Aedes-borne diseases. Due to the spatial nature of the intervention, intervention effects can be spatio-temporally heterogeneous. Yet, most evaluations of field-based technologies rely on average treatment effects, which preclude characterization and understanding of treatment effect heterogeneities and the factors influencing it. Methods: Here, we developed a causal inference framework using distributional synthetic controls to explicitly account for spatio-temporal trap-level mosquito abundance data to ascertain the entomological efficacy of Wolbachia in suppressing Ae. aegypti abundance. This method is able to construct counterfactual distributions of intervened areas, provide detailed comparisons to actual distributions and quantify treatment effects of the intervention on mosquito abundance over different quantiles. By employing our framework to trap-level mosquito abundance data from 57,990 unique mosquito traps routinely maintained and measured twice a week, and a large-scale field trial of Wolbachia incompatible-insect technique coupled with sterile insect technique (IIT-SIT) in Singapore, we (1) quantified heterogeneous treatment effects for IIT-SIT across the time-since-intervention, over the traps’ historical mosquito abundance, over calendar time, (2) quantified whether elimination of wild-type Aedes aegypti was possible in intervention locations and (3) addressed if suppressive effects in spillover locations adjacent to directly intervened locations were heterogeneous. Results: IIT-SIT interventions led to a strong suppressive effect on adult Aedes aegypti abundance. From the onset of intervention in directly treated locations, sector-specific intervention effectiveness (IE) ranged from 24.04% in the earliest treatment period, and reached 86.08% in the latest treatment period. Raw reductions in aegypti abundance were also found to increase over time as sectors were intervened over longer time periods. In spillover sectors, IE was lower in magnitude and more variable, but average IE reached a maximum of 78.08% in 2-years post-treatment. Wolbachia interventions also led to an increase in the percentage of traps recording no mosquitoes from 6.8% at the start of intervention to 33.01% 124-weeks post-intervention. We found that IE was higher in sectors with lower historical mosquito abundance. However, IE converged across sectors with different historical mosquito abundance as intervention time increased. Conclusion: This study revealed spatial heterogeneities in suppressing wild-type female Ae. aegypti by IIT-SIT and provided strong evidence that IIT-SIT can drastically suppress wild-type Ae. aegypti populations despite heterogeneous treatment effects over time. Author summary: Aedes-borne diseases transmit across tropical and sub-tropical regions of the world, with the most important being dengue threatening half the global population. Vector control plays a fundamental role in reducing transmission and infection by reducing vector populations. Previous studies have demonstrated that a promising biological control technique called IIT-SIT can efficiently suppress Ae. aegypti population and have examined its effects across different durations of suppression. However, less attention has been given on how this suppressive effect varies spatially. We therefore developed a framework which can characterize differences in these intervention effects on a fine-spatial scale. This framework can provide new insights on the spatial heterogeneity of the treatment on mosquito abundance. We identified a general suppression pattern across different levels of mosquito abundance and showed that elimination of wild-type mosquitoes was not possible in the intervened areas. We also demonstrated similar but weaker suppression effects in locations adjacent to intervention areas. These findings illustrate the spatial heterogeneity of vector control and can provide guidance for optimizing resource allocation in future intervention implementation.