A Cluster-randomized Trial to EValuate the Efficacy of Wolbachia-InfecTed Aedes Aegypti Mosquitoes in Reducing the Incidence of Arboviral Infection in Brazil (EVITA Dengue)

NCT ID: NCT04514107

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 5757 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-09
• Study Completion Date: 2024-10-29

Brief Summary

This is a cluster randomized controlled trial (CRCT) to evaluate the efficacy of Wolbachia-infected A. aegypti mosquito releases in reducing the burden of ARBV infection in Brazil over four years. The intervention will be the release of Wolbachia-infected A. aegypti mosquitoes. Standard control measures routinely established by the Belo Horizonte City Hall as recommended by the PNCD, will continue to be performed by the Belo Horizonte Health Department (Zoonoses Management) in all clusters, that is, the standard control measures will be carried out throughout the city of Belo Horizonte, independent of this clinical study. Wolbachia-infected A. aegypti will be deployed by releasing adult mosquitoes in pre-determined, thoroughly spaced release points in easily accessible roads described in a release map. A release map will be generated for each cluster and the numbers of release points will be determined by population density, surface area and mosquito abundance. Wolbachia-infected A. aegypti mosquitoes will be deployed across intervention clusters in two stages: 1) a 4 month establishment stage in which most of the releases will occur and 2) followed by an 8 month consolidation stage in which the abundance of Wolbachia-infected mosquitoes will be measured and remedial deployments will be completed, if needed, with the aim of achieving a high prevalence of Wolbachia amongst A. aegypti mosquitoes in intervention clusters within 12 months from the start of the release. The goal is to reach a Wolbachia prevalence of 60% or higher. Monitoring of Wolbachia prevalence in the cluster will continue throughout the study period, but no further mosquito deployments will occur after the consolidation stage is complete. The primary objective is to evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of ARBV infection compared to standard Aedes vector control measures alone.

Detailed Description

This is a cluster randomized controlled trial (CRCT) to evaluate the efficacy of Wolbachia-infected A. aegypti mosquito releases in reducing the burden of ARBV infection in Brazil over four years. The intervention will be the release of Wolbachia-infected A. aegypti mosquitoes. Standard control measures routinely established by the Belo Horizonte City Hall as recommended by the PNCD, will continue to be performed by the Belo Horizonte Health Department (Zoonoses Management) in all clusters, that is, the standard control measures will be carried out throughout the city of Belo Horizonte, independent of this clinical study. Wolbachia-infected A. aegypti will be deployed by releasing adult mosquitoes in pre-determined, thoroughly spaced release points in easily accessible roads described in a release map. A release map will be generated for each cluster and the numbers of release points will be determined by population density, surface area and mosquito abundance. Wolbachia-infected A. aegypti mosquitoes will be deployed across intervention clusters in two stages: 1) a 4 month establishment stage in which most of the releases will occur and 2) followed by an 8 month consolidation stage in which the abundance of Wolbachia-infected mosquitoes will be measured and remedial deployments will be completed, if needed, with the aim of achieving a high prevalence of Wolbachia amongst A. aegypti mosquitoes in intervention clusters within 12 months from the start of the release. The goal is to reach a Wolbachia prevalence of 60% or higher. Monitoring of Wolbachia prevalence in the cluster will continue throughout the study period, but no further mosquito deployments will occur after the consolidation stage is complete.

Of note, due to widespread dengue epidemic in Brazil and the introduction of the dengue vaccination campaign by the Ministry of Health, all children ages 10-14 received Odenga. Since vaccination precludes the ability to assess for flavivirus seroconversion, participants eligible to receive the vaccination, the Year 5 annual sample may be collected earlier than the study window. The Visit 05 sample for these subjects will be obtained prior or up to 14 days after dengue vaccination (the optimal cut-off time for the detection of vaccine-induced neutralizing antibodies is to be determined and will be explained in more detail in the SAP). Those who have this earlier visit will also have Visit 06 during the expected study window. The Visit 06 sample will be used for serologic assay wherever available and appropriate considering dengue vaccination status and Visit 05 samples in all other circumstances.

The primary objective is to evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduce the sero-incidence of ARBV infection compared to standard Aedes vector control measures alone. The Secondary objectives are 1.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of ARBV infection, inferred from model-based reconstruction of serological dynamics compared to standard Aedes vector control measures alone; 2.) To evaluate whether releases of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of FLAV or CHIKV infection amongst individuals who are seronegative to each of these viruses, respectively, at study entry, compared to standard Aedes vector control measures alone; 3.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the overall sero-incidence of FLAV (DENV + ZIKV) infection; 4.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of DENV infection; 5.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of ZIKV infection; 6.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of CHIKV infection among those who are CHIKV seronegative at baseline; 7.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of DENV infection amongst individuals who are seropositive to any DENV serotype(s) at study entry, compared to standard Aedes vector control measures alone; 8.) To use model-based geostatistics to estimate the proportion and abundance of Wolbachia-infected and wildtype Aedes aegypti mosquitoes in intervention clusters during the study period; 9.) To use model-based geostatistics to estimate the proportion and abundance of Wolbachia-infected and wildtype Aedes aegypti mosquitoes in control clusters during the study period.

Conditions

Dengue Fever

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Control

29 school-based clusters of healthy individuals, age 6-11, exposed to standard vector control efforts recommended by the Brazilian National Dengue Control Program (PNCD). n=1740

Group Type: ACTIVE_COMPARATOR

Brazilian National Dengue Control Program

Intervention Type: OTHER

This program has 4 basic principles: 1) Adequate case finding, classification and treatment; 2) Epidemiological surveillance and reporting of all cases; 3) Mobilization and communication of risks to the public; 4) mosquito monitoring and control which consists fundamentally of detection of larva using a rapid larval index (LIRAa) followed by removal of breeding sites and local spraying.

Intervention

29 school-based clusters of healthy individuals, age 6-11, exposed to standard vector control efforts recommended by the Brazilian National Dengue Control Program (PNCD) and Wolbachia-infected Aedes aegypti (wMel) mosquitoes. n=1740

Group Type: EXPERIMENTAL

Brazilian National Dengue Control Program

Intervention Type: OTHER

This program has 4 basic principles: 1) Adequate case finding, classification and treatment; 2) Epidemiological surveillance and reporting of all cases; 3) Mobilization and communication of risks to the public; 4) mosquito monitoring and control which consists fundamentally of detection of larva using a rapid larval index (LIRAa) followed by removal of breeding sites and local spraying.

Wolbachia-infected Aedes aegypti

Intervention Type: OTHER

Brazilian strain of Aedes aegypti infected with Wolbachia pipientis released into geographic clusters.

Interventions

Brazilian National Dengue Control Program

This program has 4 basic principles: 1) Adequate case finding, classification and treatment; 2) Epidemiological surveillance and reporting of all cases; 3) Mobilization and communication of risks to the public; 4) mosquito monitoring and control which consists fundamentally of detection of larva using a rapid larval index (LIRAa) followed by removal of breeding sites and local spraying.

Intervention Type: OTHER

Wolbachia-infected Aedes aegypti

Brazilian strain of Aedes aegypti infected with Wolbachia pipientis released into geographic clusters.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Children aged 6-11 years at enrollment.

2. Child's parent or legal guardian agrees to provide written informed consent.

3. Child agrees to provide informed assent.

4. Child is enrolled in a public school selected for this trial (and which define the clusters).

5. Child resides within geographic boundaries at least 5 days a week in the cluster area corresponding to his/her school.

Exclusion Criteria

1. Children planning to move outside of the cluster boundary within the study period.

2. Child has poor venous access.

3. Child has received an experimental or licensed vaccine against dengue, Zika or chikungunya at enrollment. Participants who received a dengue, Zika or CHIK vaccine after enrollment will not be excluded.

4. Child has any medical condition that would prevent them from completing a blood draw.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Universidade Federal de Minas Gerais, Instituto de Ciencias Biologicas, Department of Biochemistry and Immunology

Belo Horizonte, Minas Gerais, Brazil

Countries

Brazil

References

Collins MH, Potter GE, Hitchings MDT, Butler E, Wiles M, Kennedy JK, Pinto SB, Teixeira ABM, Casanovas-Massana A, Rouphael NG, Deye GA, Simmons CP, Moreira LA, Nogueira ML, Cummings DAT, Ko AI, Teixeira MM, Edupuganti S. EVITA Dengue: a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil. Trials. 2022 Mar 2;23(1):185. doi: 10.1186/s13063-022-05997-4.

Reference Type: DERIVED

PMID: 35236394 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

HHSN272201300018I

Identifier Type: -

Identifier Source: secondary_id

17-0111

Identifier Type: -

Identifier Source: org_study_id