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)

NCT04514107 | Completed

• 2 other identifiers: 17-0111HHSN272201300018I
• Study Type: interventional
• Target: 5,757
• Locations: 1 country
• Sites: 1

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.

Conditions

Dengue Fever

Keywords

Arbovirus; Brazil; Chikungunya; Cluster-Randomized; Dengue; Flavivirus; Mosquitoes; Wolbachia-infected; Zika virus

Outcome Measures

Primary Outcomes (1)

• Incidence of arbovirus (ARBV) infection

  Defined as seroconversion to flavivirus (FLAV) or chikungunya virus (CHIKV), as detected during annual serological evaluations.

  Year 1 through Year 5

Secondary Outcomes (9)

• Cluster level of prevalence and abundance of Wolbachia-infected and wildtype Aedes aegypti adults in control clusters

  From Year 1 through Year 5

• Cluster level prevalence and abundance of Wolbachia-infected and wildtype Aedes aegypti adults in intervention clusters

  From Year 1 through Year 5

• Incidence of arbovirus (ARBV) infections, specifically due to flavivirus (FLAV) or chikungunya virus (CHIKV)

  Year 1 through Year 5

• Incidence of Chikungunya virus (CHIKV) infection is defined by seroconversion to CHIKV

  Year 1 through Year 5

• Incidence of Dengue virus (DENV) infection as defined by seroconversion to DENV

  Year 1 through Year 5

Study Arms (2)

Control

ACTIVE COMPARATOR

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

Other: Brazilian National Dengue Control Program

Intervention

EXPERIMENTAL

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

Other: Brazilian National Dengue Control Program; Other: Wolbachia-infected Aedes aegypti

Interventions

Brazilian National Dengue Control Program 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.

Control; Intervention

Wolbachia-infected Aedes aegypti OTHER

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

Intervention

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 6-11 years at enrollment.
• Child's parent or legal guardian agrees to provide written informed consent.
• Child agrees to provide informed assent.
• Child is enrolled in a public school selected for this trial (and which define the clusters).
• Child resides within geographic boundaries at least 5 days a week in the cluster area corresponding to his/her school.

You may not qualify if:

• Children planning to move outside of the cluster boundary within the study period.
• Child has poor venous access.
• 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.
• Child has any medical condition that would prevent them from completing a blood draw.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

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

Belo Horizonte, Minas Gerais, 31275-030, Brazil

Location

Related Publications (1)

• 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.

  PMID: 35236394 DERIVED

MeSH Terms

Conditions

Dengue; Chikungunya Fever; Zika Virus Infection

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Alphavirus Infections; Togaviridae Infections

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 14, 2020
• Study Start: September 9, 2020
• Primary Completion: October 29, 2024
• Study Completion: October 29, 2024
• Last Updated: November 25, 2025

Record last verified: 2024-05-29

Locations

BR (1)