Effectiveness ofWolbachia-infected mosquito deployments in reducing the incidence of dengue and otherAedes-borne diseases in Niterói, Brazil: a quasi-experimental study

Abstract

Background: The introduction of the bacterium Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Evidence of a reduction in dengue case incidence following field releases of wMel-infected Ae. aegypti has been reported previously from a cluster randomised controlled trial in Indonesia, and quasi-experimental studies in Indonesia and northern Australia. Methods: Following a period of intensive community engagement, deployments of adult wMel-infected Ae. aegypti mosquitoes were conducted in Niterói, Brazil during 2017 − 2019. Deployments were phased across four release zones, with a total area of 83 km2 and a residential population of approximately 373,000. A quasi-experimental design was used to evaluate the effectiveness of wMel deployments in reducing dengue and chikungunya incidence. An untreated control zone was pre-defined, which was comparable to the intervention area in historical dengue trends. The wMel intervention effect was estimated by controlled interrupted time series analysis of monthly dengue and chikungunya case notifications to the public health surveillance system before, during and after releases, from release zones and the control zone. Results: Three years after commencement of releases, wMel introgression into local Ae. aegypti populations was heterogeneous throughout Niterói, reaching a high prevalence (>80%) in the earliest release zone, and more moderate levels (prevalence 40 -70%) elsewhere. Despite this spatial heterogeneity in entomological outcomes, the wMel intervention was associated with a 69% reduction in dengue incidence (95% confidence interval 54%, 80%) and a 60% reduction in chikungunya incidence (95%CI 21%, 80%), in the aggregate release area compared with the pre-defined control area. This significant intervention effect on dengue was replicated across all four release zones, and in three of four zones for chikungunya. Conclusions: We demonstrate that wMel Wolbachia can be successfully introgressed into Ae. aegypti populations in a large and complex urban setting, and that a significant public health benefit from reduced incidence of dengue and chikungunya accrues even where the prevalence of wMel in local mosquito populations is moderate and spatially heterogeneous. These findings are consistent with the results of randomised and non-randomised field trials in Indonesia and northern Australia, and demonstrate the effectiveness of the Wolbachia biocontrol method as a multivalent intervention against both dengue and chikungunya.

Large-scale deployment and establishment ofWolbachiainto theAedes aegyptipopulation in Rio de Janeiro, Brazil

“…With continuous improvement of rearing and release technology, it could be amplified to cover city-wide territories in short time. As preliminary disease impact studies suggest (Durovni et al 2020;Pinto et al 2021), one could foresee a significant reduction in the incidence of dengue and other arboviral diseases in Rio de Janeiro and nearby Niteroi, fulfilling the main goal of current trials and cementing Wolbachia as an efficient and sustainable solution vector control in Brazil.…”

“…This effect, however, can only be verified after a continued longterm monitoring of field populations, whose data may also indicate the necessity to apply topic release boosts at those neighborhoods with persistent low rates. These considerations are part of challenging large-scale release interventions, which are still incipient here in Brazil and in other parts of the world (Schmidt et al 2017;Ryan et al 2019;Tantowijoyo et al 2020). As a result of accumulating data from current trials, we shall better understand the factors underlying invasion dynamics and optimize future strategies.…”

“…Importantly, Wolbachia's high prevalence rates in the field, as well as intrinsic CI and PI, were sustained in the long-term, providing the necessary conditions to reduce dengue incidence in subsequent epidemiological assessments (O'Neill et al 2019;Ryan et al 2019). Corroborating the Australian findings, recent trials in Indonesia (Tantowijoyo et al 2020) and Southeastern Brazil (Garcia et al 2019;Gesto et al 2020) have also reported the successful invasion and establishment of wMel at some localities, with preliminary evidence of arboviral disease reduction (Indriani et al 2020;Durovni et al 2020;Pinto et al 2021). In the particular context of Southeastern Brazil, trials have initially targeted small neighborhoods of Rio de Janeiro and the nearby city Niterói, following adult (Garcia et al 2019) or egg deployment methods (Gesto et al 2020).…”

“…Hoffmann et al 2011;Ary A. Hoffmann et al 2014). Importantly, Wolbachia's high prevalence rates in the field, as well as intrinsic CI and PI, were sustained in the long-term, providing the necessary conditions to reduce dengue incidence in subsequent epidemiological assessments (O'Neill et al 2019;Ryan et al 2019). Corroborating the Australian findings, recent trials in Indonesia (Tantowijoyo et al 2020) and Southeastern Brazil (Garcia et al 2019;Gesto et al 2020) have also reported the successful invasion and establishment of wMel at some localities, with (which was not certified by peer review) is the author/funder.…”

Combating mosquito-borne diseases using genetic control technologies

“…High Wolbachiainfection rates were sustained for 6 months following release in dengue virus (DENV)-endemic Yogyakarta, Indonesia, where Wolbachia-infected adults or eggs were released over 20 or 24 weeks, respectively 14 and, importantly, resulted in a significant reduction in dengue incidence in the treatment area 15,16 . High Wolbachia-infection rates (>80%) were also sustained for more than 2 years after release in DENV-endemic Kuala Lumpur, Malaysia 17,18 and recently in Brazil, where significant reductions in dengue, Zika, and chikungunya incidence were also observed in Wolbachia intervention areas 19 . In general, Wolbachia-based population modification strategies appear to require fewer releases than IIT strategies and allow the release of both sexes of Wolbachia-infected mosquitoes, enabling long-term persistence in the environment (Fig.…”