Effectiveness of Wolbachia-infected mosquito deployments in reducing the incidence of dengue and other Aedes-borne diseases in Niterói, Brazil: A quasi-experimental study.

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.

The impact of large-scale deployment of Wolbachia mosquitoes on dengue and other Aedes-borne diseases in Rio de Janeiro and Niterói, Brazil: study protocol for a controlled interrupted time series analysis using routine disease surveillance data.

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 km 2 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.

Correction to: Socioeconomic and demographic characterization of an endemic malaria region in Brazil by multiple correspondence analysis.

After publication of the article [1], it has been brought to our attention that the y-axis of Fig. 6 has been labeled incorrectly. It should read "linear predictor". This has now been corrected in the original article.

Socioeconomic and demographic characterization of an endemic malaria region in Brazil by multiple correspondence analysis.

BACKGROUND: In the process of geographical retraction of malaria, some important endemicity pockets remain. Here, we report results from a study developed to obtain detailed community data from an important malaria hotspot in Latin America (Alto Juruá, Acre, Brazil), to investigate the association of malaria with socioeconomic, demographic and living conditions. METHODS: A household survey was conducted in 40 localities (n = 520) of Mâncio Lima and Rodrigues Alves municipalities, Acre state. Information on previous malaria, schooling, age, gender, income, occupation, household structure, habits and behaviors related to malaria exposure was collected. Multiple correspondence analysis (MCA) was applied to characterize similarities between households and identify gradients. The association of these gradients with malaria was assessed using regression. RESULTS: The first three dimensions of MCA accounted for almost 50% of the variability between households. The first dimension defined an urban/rurality gradient, where urbanization was associated with the presence of roads, basic services as garbage collection, water treatment, power grid energy, and less contact with the forest. There is a significant association between this axis and the probability of malaria at the household level, OR = 1.92 (1.23-3.02). The second dimension described a gradient from rural settlements in agricultural areas to those in forested areas. Access via dirt road or river, access to electricity power-grid services and aquaculture were important variables. Malaria was at lower risk at the forested area, OR = 0.55 (1.23-1.12). The third axis detected intraurban differences and did not correlate with malaria. CONCLUSIONS: Living conditions in the study area are strongly geographically structured. Although malaria is found throughout all the landscapes, household traits can explain part of the variation found in the odds of having malaria. It is expected these results stimulate further discussions on modelling approaches targeting a more systemic and multi-level view of malaria dynamics.

Better to Be in Bad Company than to Be Alone? Aedes Vectors Respond Differently to Breeding Site Quality in the Presence of Others.

This study focuses on two competing species, Aedes aegypti and Aedes albopictus (Diptera: Culicidae), both invasive mosquitoes of the New World. Context-specific competition between immature forms inside containers seems to be an important determinant of the coexistence or displacement of each species in different regions of the world. Here, competition experiments developed at low density (one, two or three larvae) and receiving four different resource food concentration, were designed to test whether Ae. albopictus and Ae. aegypti respond differently to competition, and whether competition can be attributed to a simple division of resources. Three phenotypic traits - larval development, adult survival under starvation and wing length - were used as indicators of performance. Larvae of neither species were limited by resource concentration when they were alone, unlike when they developed with competitors. The presence of conspecifics affected Ae. aegypti and Ae. albopictus, inducing slower development, reduced survival and wing length. The response to resource limitation was different when developing with heterospecifics: Ae. aegypti developing with one heterospecific showed faster development, producing smaller adults with shorter lives, while in the presence of two competitors, development increased and adults lived longer. Aedes albopictus demonstrated a better performance when developing with heterospecifics, with no loss in their development period and improved adult survival. Overall, our results suggest that response to competition can not simply be attributed to the division of resources, and that larvae of both species presented large phenotypic plasticity in their response to the presence or absence of heterospecifics and conspecifics.