Impact of Project Wolbachia - Singapore on Dengue Incidence

Assessing the Efficacy of Male Wolbachia-infected Mosquito Deployments to Reduce Dengue Incidence in Singapore: a Cluster Randomized Controlled Trial

The study is a cluster-randomised controlled trial set in Singapore, to assess if the deployment of male Wolbachia-infected Aedes aegypti mosquitoes can reduce dengue incidence in intervention clusters.

Study Overview

• Status: Completed
• Conditions: Dengue
• Intervention / Treatment: Biological: Biological (Male Wolbachia-infected Aedes aegypti)

Detailed Description

The study is designed as a parallel, two-arm, non-blinded cluster-randomised controlled trial to be conducted in high-rise public housing estates in Singapore. The aim is to determine whether large-scale deployment of male Wolbachia-infected Ae. aegypti mosquitoes can significantly reduce dengue incidence in intervention clusters. The investigators will use the cluster-randomised design, with the study area comprising 15 clusters with a total area of 10.9 km2, covering approximately 722,000 residents in 1,700 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.

• Study Type: Interventional
• Enrollment (Actual): 724428
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • National Environment Agency

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Dengue-suspected patients living in the intervention and non-intervention clusters whose blood samples are collected by a national network of diagnostic laboratories that support private clinics, public polyclinics, or public/private hospitals.
• Test positive cases: Patients with virologically confirmed DENV infection through RT-qPCR, testing positive for NS1 antigen or IgM. A positive test for any of the three assays would classify the patient as a dengue case.
• Test negative controls: Patients with negative test results for DENV through RT-qPCR, NS1 antigen ELISA, or DENV IgM.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention clusters; Residential areas that receive releases of male Wolbachia-infected Aedes aegypti	Biological: Biological (Male Wolbachia-infected Aedes aegypti); Releases of male Wolbachia-infected Aedes aegypti mosquitoes
No Intervention: Non-intervention clusters; Residential areas that do not receive releases of male Wolbachia-infected Aedes aegypti

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Odds ratio of Wolbachia exposure distribution among laboratory-confirmed reported dengue cases compared to test-negative controls	Dengue cases and dengue test-negative controls data will be obtained from the national surveillance network of diagnostic laboratories which receive samples for dengue testing.	Up to 3 years
Laboratory-confirmed reported dengue case counts normalized by population size in intervention versus non-intervention clusters	Dengue cases data will be obtained from the national surveillance network of diagnostic laboratories which receive samples for dengue testing.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Ae. aegypti/Ae. albopictus mosquitoes	Data will be obtained from the national gravitrap surveillance system	Up to 3 years
Public Attitudes, Perceptions & Knowledge (APK) of Wolbachia and other vector control interventions	Sentiment surveys pre-trial and during the course of the trial, using true/false and Likert-type scales. Higher scores mean better outcomes.	Up to 3 years

Collaborators and Investigators

• Sponsor: National Environment Agency, Singapore
• Collaborators: Ministry of Health, Singapore
• Investigators: Principal Investigator: Lee Ching Ng, PhD, Group Director (Environmental Health Institute)

Publications and helpful links

General Publications

• Anders KL, Indriani C, Ahmad RA, Tantowijoyo W, Arguni E, Andari B, Jewell NP, Rances E, O'Neill SL, Simmons CP, Utarini A. The AWED trial (Applying Wolbachia to Eliminate Dengue) to assess the efficacy of Wolbachia-infected mosquito deployments to reduce dengue incidence in Yogyakarta, Indonesia: study protocol for a cluster randomised controlled trial. Trials. 2018 May 31;19(1):302. doi: 10.1186/s13063-018-2670-z.
• Utarini A, Indriani C, Ahmad RA, Tantowijoyo W, Arguni E, Ansari MR, Supriyati E, Wardana DS, Meitika Y, Ernesia I, Nurhayati I, Prabowo E, Andari B, Green BR, Hodgson L, Cutcher Z, Rances E, Ryan PA, O'Neill SL, Dufault SM, Tanamas SK, Jewell NP, Anders KL, Simmons CP; AWED Study Group. Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue. N Engl J Med. 2021 Jun 10;384(23):2177-2186. doi: 10.1056/NEJMoa2030243.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2022
• Primary Completion (Actual): September 13, 2024
• Study Completion (Actual): September 13, 2024

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: August 16, 2022
• First Posted (Actual): August 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: IRB024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No