METHODS: We used the synthetic control method (SCM) under assumption of partial interference to evaluate the direct and spillover PEs of Wolbachia-mediated introgression in a long-running operational trial of the intervention in Malaysia. Synthetic controls (SCs), which comprise of a weighted sum of non-spillover controls, were constructed for each directly-treated and spillover site in the pre-intervention period to account for historical imbalances in dengue risk and risk trajectories. SCs were compared to directly/spillover-treated sites to estimate the impact of Wolbachia-introgression on dengue incidence across each site, calendar year and intervention time. Robustness checks, including visual inspections, root-mean-square error (RMSE) calculations, in-space and in-time placebo checks, and permutation tests, were used to inspect the model's ability in attributing dengue incidence reductions to the Wolbachia interventions.
FINDINGS: The direct and spillover PEs of Wolbachia on dengue incidence were expressed as a percentage reduction of dengue incidence, or the absolute case reductions, by comparing SCs to actual intervention/spillover sites. Findings indicate a direct reduction in dengue incidence by 64.35% (95% CI: 63.50-66.71, p Hoffmann et al. (2024) study was funded by the Wellcome Trust Awards 226166, 108508, 202888 and the Ministry of Health Malaysia NMRR-16-297-28898.