Human and mosquito movement can lead to underestimation of the intervention effect in trials of vector interventions; as such, the protective efficacy of Wolbachia is likely even higher than reported in the primary trial results.
Deployments of wMel-infected Aedes aegypti mosquitoes resulted in an 83% reduction in the application of perifocal insecticide spraying, consistent with lower dengue case notifications in wMel-treated areas. These results show that the Wolbachia intervention effect demonstrated previously in a cluster randomised trial was also measurable from routine surveillance data.
We propose the log-contrast estimator that can eliminate bias caused by differential healthcare-seeking behavior in cluster-randomized test-negative designs and demonstrate how to improve precision by adjusting for covariates.
Introgression of wMel into A. aegypti populations was effective in reducing the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants.
We demonstrate a significant reduction in dengue incidence following successful introgression of Wolbachia into local Ae. aegypti populations in an endemic setting in Indonesia. These findings are consistent with previous field trials in northern Australia, and support the effectiveness of this novel approach for dengue control.
In cluster randomized trials (CRTs), the outcome of interest is often a count at the cluster level. This occurs, for example, in evaluating an intervention with the outcome being the number of infections of a disease such as HIV or dengue or the number of hospitalizations in the cluster. Standard practice analyzes these counts through cluster outcome rates using an appropriate denominator (eg, population size). However, such denominators are sometimes unknown, particularly when the counts depend on a passive community surveillance system. We consider direct comparison of the counts without knowledge of denominators, relying on randomization to balance denominators. We also focus on permutation tests to allow for small numbers of randomized clusters. However, such approaches are subject to bias when there is differential ascertainment of counts across arms, a situation that may occur in CRTs that cannot implement blinded interventions. We suggest the use of negative control counts as a method to remove, or reduce, this bias, discussing the key properties necessary for an effective negative control. A current example of such a design is the recent extension of test-negative designs to CRTs testing community-level interventions. Via simulation, we compare the performance of new and standard estimators based on CRTs with negative controls to approaches that only use the original counts.When there is no differential ascertainment by intervention arm, the count-only approaches perform comparably to those using debiasing negative controls. However, under even modest differential ascertainment, the count-only estimators are no longer reliable.
Vector-borne diseases are a growing threat to global health. I help develop statistical methods to rigorously evaluate the impact of novel preventive interventions.
Rio de Janeiro and Niterói municipalities in southeastern Brazil experience large dengue epidemics every 2 to 5 years, with 100,000 cases notified in epidemic years. Costs of vector control and direct and indirect costs due to the Aedes-borne diseases dengue, chikungunya and Zika were estimated to total $650 million USD in 2016, but traditional vector control strategies have not been effective in preventing arboviral disease outbreaks. The Wolbachia method is a novel and self-sustaining approach for the biological control of arboviral diseases, in which the transmission potential of Ae. aegypti mosquitoes is reduced by stably transfecting them with the Wolbachia bacterium. This paper describes a study protocol for evaluating the effect of large-scale non-randomised releases of Wolbachia mosquitoes on the incidence of dengue, Zika and chikungunya in the municipalities of Niterói and Rio de Janeiro. This follows a lead-in period since 2014 involving intensive community engagement, regulatory and public approval, entomological surveys, and small-scale pilot releases.