Impact of Project Wolbachia - Singapore on Dengue Incidence

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Dengue

Intervention / Treatment
-----------------
* Biological: Biological (Male Wolbachia-infected Aedes aegypti)


Participation Criteria
=================
Eligibility Criteria
-----------------
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.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel, two-arm, non-blinded cluster-randomised controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention clusters<br>Residential areas that receive releases of male Wolbachia-infected Aedes aegypti | Biological: Biological (Male Wolbachia-infected Aedes aegypti)<br>* Releases of male Wolbachia-infected Aedes aegypti mosquitoes<br>|
| No Intervention: Non-intervention clusters<br>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 |