Efficacy ofWolbachia-mediated sterility to suppress adultAedes aegyptipopulations

Abstract

Incompatible insect technique coupled with sterile insect technique (IIT-SIT) via releases of sterile maleWolbachia-infected mosquitoes is a promising tool for dengue control. In a six-year trial from 2016 to 2022, comprising 10.35 km2of high-rise housing estates and 607,872 residents, we designed a synthetic control study methodology to assess the efficacy of IIT-SIT in reducing adult femaleAedes aegyptipopulations, using data from a large, routinely collected, nationwide surveillance system of 57,990 unique mosquito traps in public housing estates.We demonstrated thatWolbachia-based IIT-SIT dramatically reduces wildtypeAedes aegyptipopulations by an average of 60.64% (95% CI: 59.59%–61.44%) and 79.37% (95% CI: 78.85%–79.87%) in 3, 6 months of releases and eventually 90.17% (95% CI: 89.92%–90.42%) in 12 and more months of releases. We further found a smaller but non-negligible suppression effect which gradually increased over time (47.91%, 95% CI: 47.29%–48.52%) in adjacent, non-intervention sites. Our results demonstrate the potential of IIT-SIT for strengthening dengue control in tropical cities, where dengue burden is the greatest.

Wolbachiaincompatible insect technique program optimization over large spatial scales using a process-based model of mosquito metapopulation dynamics

“…Given the effects of adult mosquito migration on mosquito abundance and treatment program efficacy, the framework was designed to factor in migration by explicitly defining the study area as a grid of vertical hexagons. A single hexagon approximates a planning sector, which is the primary spatial resolution used for planning the surveillance and control of environment-related infectious diseases in Singapore (Bansal et al, 2023). Mosquitoes are modeled to mix homogeneously within a hexagon, and some adult mosquitoes migrate out of a hexagon into its six neighbors at a total daily rate of υ ; conversely adult mosquitoes migrate into a hexagon from each of its six neighbors at a daily rate of υ /6.…”

“…The grid of vertical hexagons was designed to span the main island of Singapore, Pulau Ujong. Each hexagon was designed to have a side length of 184m to match the average planning sector area of 0.088km 2 (Bansal et al, 2023). A hexagon was classified as a land or water one based on the geospatial subzone in which its center lies.…”

“…When male insects infected with Wolbachia mate with females that either lack Wolbachia or have different Wolbachia strains, cytoplasmic incompatibility can cause the offspring to die during the early stages of embryonic development (Engelstädter & Telschow, 2009). Wolbachia- mediated cytoplasmic incompatibility has been tested in field trials in China, the USA, and Singapore through the incompatible insect technique (IIT), where only male mosquitoes with the Wolbachia infection are released, and has been found to effectively suppress the mosquito population (Zeng et al, 2022; Crawford et al, 2020; The Project Wolbachia - Singapore Consortium & Ng, 2021; Bansal et al, 2023) and consequently reduce dengue incidence (Lim et al, 2023; Lim et al, 2024). A cluster-randomized controlled trial is also underway in Singapore to provide gold-standard evidence of the technology’s epidemiological efficacy (Ong et al, 2022).…”

“…In addition to playing a significant role in the mosquito life cycle (Reinhold et al, 2018; Alto & Juliano, 2001), climatic factors such as temperature have been found to impact the intervention efficacy of Wolbachia replacement programs (Vásquez et al, 2023), and the same could hold for IIT programs. Prior evidence from randomized controlled trials and field trials also suggest that the migration of Wolbachia mosquitoes in treatment boundary areas has non-negligible effects on both IIT as well as replacement programs (Bansal et al, 2023; Utarini et al, 2021), which makes the characterization of mosquito population dynamics over both spatial and temporal scales important.…”

“…We employed the model to study the intervention efficacy of various release optimization strategies for an existing Wolbachia IIT program that targets Aedes aegypti mosquitoes. We used Singapore as the study site because it has an established network of mosquito surveillance traps which systematically collects national data on mosquito abundance (Ong et al, 2020), and extensive Wolbachia IIT field trial information for model validation purposes (The Project Wolbachia - Singapore Consortium & Ng, 2021; Bansal et al, 2023). Using the model, we sought to understand the consequences of:…”