Ignoring transmission dynamics leads to underestimation of the impact of a novel intervention against mosquito-borne disease

Wolbachia is an intracellular bacterium that many hope could have a major impact on dengue and other mosquito-borne diseases that are notoriously difficult to control. The balance of future investments in Wolbachia versus other public health needs will be informed to a great extent by efficacy estimates from large-scale trials, which can be affected by multiple sources of bias. We used mathematical models to quantify the possible magnitude of these biases, finding that efficacy would have been severely underestimated in a recent trial in Indonesia if the spatial scale of clusters had been smaller than it was. We also identified a previously unrecognized source of bias owing to the coupled nature of transmission dynamics across clusters. This too led to a consistent underestimate of the protection afforded by Wolbachia. Taken together, our findings suggest that this intervention may be even more promising than currently recognized.