No 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. Methodology/Principal findings Following pilot releases in 2015–2016 and 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, chikungunya and Zika 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, chikungunya and Zika case notifications to the public health surveillance system before, during and after releases, from release zones and the control zone. 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%, 79%), a 56% reduction in chikungunya incidence (95%CI 16%, 77%) and a 37% reduction in Zika incidence (95%CI 1%, 60%), 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, though not in individual release zones for Zika. Conclusions/Significance 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 Aedes-borne disease 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 are supportive of the Wolbachia biocontrol method as a multivalent intervention against dengue, chikungunya and Zika.

EditorialDengue virus type 4 arrives in the state of Rio de Janeiro: a challenge for epidemiological surveillance and control Dengue virus type 4 (DENV-4) re-emerged in the state of Roraima (RR), a remote state in the extreme Northwest of Brazil, in July 2010 at the height of the rainy season. This serotype had not been detected in the country for almost 30 years, when DENV-4 and DENV-1 caused a limited outbreak in RR's capital city Boa Vista in [1981][1982] with 11,000 reported cases. The reinvasion of DENV-4 in July 2010 was not followed by an epidemic in RR; less than 20 cases of DENV-4 were confirmed in this state throughout the second half of 2010. The first cases, which were considered to have been the result of the virus spreading from RR, were not registered until January 2011. First, the virus reached two states of the Northern Region, Amazonas and Pará, in January. In March, the virus was subsequently detected in the Northeast Region, first in the state of Piauí and later in the states of Pernambuco, Bahia and Ceará, and in the Southeast Region, in the states of Rio de Janeiro (RJ) and São Paulo. The arrival of this serotype in RJ eight months after its resurgence in RR, almost 5,000 km away, has important and particular epidemiological significance. Furthermore, its early detection during the course of a DENV-1 epidemic reveals the efficiency of an epidemiological surveillance.RJ is a hub for many tourist activities and is therefore connected to a large and busy roadway and railway system that allows access to the most populous part of the country. In addition, the local Aedes aegypti populations are highly susceptible to dengue virus and are generally found in high densities throughout most of the state's territory. As a result, the state is known as the most important point for the introduction and dissemination of the dengue virus in Brazil. Indeed, RJ was where the introduction and dispersion of the first cases of DENV-1 (1986; the previous invasion in 1981 was limited to Boa Vista), DENV-2 (1990) and DENV-3 (2000) took place. The recent introduction of DENV-4 in this state is of great concern because of its potential to spread to the rest of Brazil.The first cases of DENV-4 detected in RJ occurred in the Cafubá neighbourhood, in the oceanic region of the municipality of Niterói (22°52′S 43°06′W; 487,327 inhabitants), which is located in the metropolitan region of RJ, only 15 km away from the capital city. The tourist sector is one of the most promising sectors, and the water supply reaches almost all of the households in the neighbourhoods' urban areas in Niterói. However, the sewage system does not coincide with the extension of the water supply networks. A considerable portion of the Niterói population is represented by the elderly, and the aging index is the highest in the state.Curiously, the first two cases of DENV-4 in RJ were detected in two young sisters, 22 and 23 years of age, who first began to show symptoms on March 6, 2011 during a DENV-1 outbreak in the state. Both presented fever,...

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.

Background: Rio de Janeiro and Niterói are neighbouring cities in southeastern Brazil which 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 mosquito-borne disease outbreaks. The Wolbachia method is a novel and self-sustaining approach for the biological control of Aedes-borne diseases, in which the transmission potential of Aedes aegypti mosquitoes is reduced by stably transfecting them with the Wolbachia bacterium (wMel strain). This paper describes a study protocol for evaluating the effect of large-scale non-randomised releases of Wolbachia­-infected mosquitoes on the incidence of dengue, Zika and chikungunya in the two cities 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. Method: The Wolbachia releases during 2017-2019 covered a combined area of 170 km2 with a resident population of 1.2 million, across Niterói and Rio de Janeiro. Untreated areas with comparable historical dengue profiles and demographic characteristics have been identified a priori as comparative control areas in each city. The proposed pragmatic epidemiological approach combines a controlled interrupted time series analysis of routinely notified suspected and laboratory-confirmed dengue and chikungunya cases, together with monitoring of Aedes-borne disease activity utilising outbreak signals routinely used in public health disease surveillance. Discussion: If the current project is successful, this model for control of mosquito-borne disease through Wolbachia releases can be expanded nationally and regionally.