Update to: Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore.

BACKGROUND: This trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Singapore, with the aim of measuring the efficacy of male Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting with all four dengue serotypes in circulation. The trial commenced in July 2022 and is expected to conclude in September 2024. The original study protocol was published in December 2022. Here, we describe amendments that have been made to the study protocol since commencement of the trial. METHODS: The key protocol amendments are (1) addition of an explicit definition of Wolbachia exposure for residents residing in intervention sites based on the duration of Wolbachia exposure at point of testing, (2) incorporation of a high-dimensional set of anthropogenic and environmental characteristics in the analysis plan to adjust for baseline risk factors of dengue transmission, and (3) addition of alternative statistical analyses for endpoints to control for post hoc imbalance in cluster-based environmental and anthropogenic characteristics. DISCUSSION: The findings from this study will provide the first experimental evidence for the efficacy of releasing male-Wolbachia infected mosquitoes to reduce dengue incidence in a cluster-randomised controlled trial. The trial will conclude in 2024 and results will be reported shortly thereafter. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05505682. Registered on 16 August 2022. Retrospectively registered. Last updated 11 November 2023.

Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore: study protocol for a cluster-randomized controlled trial.

BACKGROUND: Dengue is a severe environmental public health challenge in tropical and subtropical regions. In Singapore, decreasing seroprevalence and herd immunity due to successful vector control has paradoxically led to increased transmission potential of the dengue virus. We have previously demonstrated that incompatible insect technique coupled with sterile insect technique (IIT-SIT), which involves the release of X-ray-irradiated male Wolbachia-infected mosquitoes, reduced the Aedes aegypti population by 98% and dengue incidence by 88%. This novel vector control tool is expected to be able to complement current vector control to mitigate the increasing threat of dengue on a larger scale. We propose a multi-site protocol to study the efficacy of IIT-SIT at reducing dengue incidence. METHODS/DESIGN: The study is designed as a parallel, two-arm, non-blinded cluster-randomized (CR) controlled trial to be conducted in high-rise public housing estates in Singapore, an equatorial city-state. The aim is to determine whether large-scale deployment of male Wolbachia-infected Ae. aegypti mosquitoes can significantly reduce dengue incidence in intervention clusters. We will use the CR design, with the study area comprising 15 clusters with a total area of 10.9 km2, covering approximately 722,204 residents in 1713 apartment blocks. Eight clusters will be randomly selected to receive the intervention, while the other seven will serve as non-intervention clusters. Intervention efficacy will be estimated through two primary endpoints: (1) odds ratio of Wolbachia exposure distribution (i.e., probability of living in an intervention cluster) among laboratory-confirmed reported dengue cases compared to test-negative controls and (2) laboratory-confirmed reported dengue counts normalized by population size in intervention versus non-intervention clusters. DISCUSSION: This study will provide evidence from a multi-site, randomized controlled trial for the efficacy of IIT-SIT in reducing dengue incidence. The trial will provide valuable information to estimate intervention efficacy for this novel vector control approach and guide plans for integration into national vector control programs in dengue-endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05505682 . Registered on 16 August 2022. Retrospectively registered.

Influence of public hesitancy and receptivity on reactive behaviours towards releases of male Wolbachia-Aedes mosquitoes for dengue control.

Singapore, a highly urbanized Asian tropical country that experiences periodic dengue outbreaks, is piloting field releases of male Wolbachia-carrying Aedes aegypti mosquitoes with the aim of suppressing urban populations of the primary dengue vector Aedes aegypti. This study proposes and assesses a model to explain the roles of hesitancy and receptivity towards Project Wolbachia-Singapore in influencing reactive mosquito prevention behaviors (reactive behaviors) towards the release of Wolbachia-Aedes mosquitoes for residents living in the release sites. Interestingly, both hesitancy and receptivity predicted greater instances of reactive behaviors. The model also examines the roles of general knowledge about Wolbachia technology, perceived severity of mosquito bites, perceived density of mosquitoes, and social responsibility as predictors of hesitancy, receptivity, and reactive behaviors towards the release of Wolbachia-Aedes mosquitoes. Hesitancy towards the project mediated the effects of general knowledge, perceived severity of mosquito bites, and perceived density of mosquitoes on reactive behaviors towards the releases, although receptivity towards the project did not. Having less knowledge about Project Wolbachia-Singapore was associated with higher hesitancy towards the project and higher likelihood of performing reactive behaviors towards the releases. Individuals who perceive mosquito bites to be more severe and think that there are more mosquitoes in their living environments were also more likely to be hesitant about the project and practice reactive behaviors. However, both hesitancy and receptivity towards the project mediated the effect of social responsibility on reactive behaviors. Receptivity towards the project was driven by social responsibility, which was also associated with reduced hesitancy towards the project. Our findings suggest that, to address the hesitancy reported by a minority of participants, future outreach efforts should focus on strengthening the public's sense of social responsibility and on tailored education campaigns targeting groups with low levels of knowledge of the project.

A Household-Based Survey to Understand Factors Influencing Awareness, Attitudes and Knowledge towards Wolbachia-Aedes Technology.

In 2016, Singapore introduced the release of male Wolbachia-Aedes mosquitoes to complement vector control efforts and suppress Aedes aegypti mosquitoes in selected study sites. With ongoing expansion of Project Wolbachia-Singapore to cover larger areas, a household-based survey was conducted between July 2019 to February 2020 in two Project Wolbachia study sites using a structured questionnaire, to evaluate current sentiments and assess the need for enhanced public messaging and engagement. The association of factors that influence awareness, attitudes, and knowledge towards the use of Wolbachia-Aedes technology was analysed using Pearson's Chi-square test and binary logistic regression. Of 500 respondents, 74.8% were aware of Project Wolbachia-Singapore. Comparatively, the level of knowledge on Wolbachia-Aedes technology was lower, suggesting knowledge gaps that require enhanced communication and messaging to address misinformation. Longer exposure to the project predicted greater awareness, whereas higher education levels predicted higher knowledge levels. Younger age groups and higher education levels were associated with high acceptance towards the project. High levels of trust and acceptance towards the project were also observed across the population. The public's positive perception of the project is a testament to the effective public communication undertaken to date and will facilitate programme expansion.

Lessons from Singapore's national weight management program, Lose To Win.

The prevalence of overweight and obesity in Singapore is lower than in most countries, but it is increasing. There is evidence health complications may appear at lower weights among Asians. We describe the evolution of a national weight management program [Lose To Win (LTW)] organized by the Singapore Health Promotion Board from 2009 to 2013. LTW is a 12-week program comprising nutrition education, physical activity and mental wellbeing sessions and interim assessments. Individuals aged 18-69 years with a body mass index (BMI) between 23 and 37.4 kg/m2 were included. Primary outcomes were change in weight and BMI from baseline to end of 12-weeks. Effectiveness of the weight loss program was assessed using non-randomized control group (delayed intervention) during LTW 2010 and 2012. LTW 2009 enrolled 285 participants from 72 worksites. LTW 2010, expanded to the community, enrolling 952 participants (641 community-based and 311 workplace-based). In LTW 2012 and 2013, 959 and 1412 participants, respectively, were recruited from the community only. Completion rates of the 12-week program varied from 49 to 88%. Average weight loss ranged from 1.3 to 3.6 kg. For rounds including a control group, weight loss was higher in the intervention than in the control group. Competition and incentives were important motivators for participation. The LTW program was well-received and effective in producing short-term weight loss. Enhancements will be done to reinforce success factors in subsequent rounds to boost participation and follow-up rates and to ensure long-term sustainability.

Extent and correlates of change in anthropometric and fitness outcomes among participants in a corporate team-based weight loss challenge in Singapore: lose to win 2009.

The authors describe a national corporate team-based weight loss intervention targeting groups of overweight/obese employees and assess its effectiveness. A 12-week weight loss program comprising nutrition education and physical activity sessions, enhanced by a nationwide media campaign, was organized by the Singapore Health Promotion Board. A total of 285 participants, forming 72 teams (1 per workplace), had their anthropometric (weight, body mass index [BMI], and body fat percentage) and fitness (fitness index score based on UKK 2-km walk test) measurements taken pre-intervention and post-intervention. Average decreases, from baseline to end of intervention, in weight, BMI, and body fat percentage were 3.58 kg, 1.32 kg/m(2), and 2.14%, respectively. The fitness index score increased by 34.1 units. Greater participation in physical activity and nutrition education sessions was associated with more beneficial anthropometric and fitness changes. The intervention was well received and effective in producing short-term weight loss. Further research needs to be done to ascertain its long-term effectiveness and generalizability.