Clinical trial NCT04514107: 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)
Official title: A Cluster-Randomized Trial to Evaluate the Efficacy of Wolbachia-Infected Aedes Aegypti Mosquitoes in Reducing the Incidence of Arboviral Infection in Brazil
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dengue Fever
Keywords: Arbovirus
Brazil
Chikungunya
Cluster-Randomized
Dengue
Flavivirus
Mosquitoes
Wolbachia-infected
Zika virus
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2020-08-14
Enrollment: 5757
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Incidence of arbovirus (ARBV) infection
timeFrame: Year 1 through Year 5
Secondary outcomes:
measure: Cluster level of prevalence and abundance of Wolbachia-infected and wildtype Aedes aegypti adults in control clusters
timeFrame: From Year 1 through Year 5
measure: Cluster level prevalence and abundance of Wolbachia-infected and wildtype Aedes aegypti adults in intervention clusters
timeFrame: From Year 1 through Year 5
measure: Incidence of arbovirus (ARBV) infections, specifically due to flavivirus (FLAV) or chikungunya virus (CHIKV)
timeFrame: Year 1 through Year 5
measure: Incidence of Chikungunya virus (CHIKV) infection is defined by seroconversion to CHIKV
timeFrame: Year 1 through Year 5
measure: Incidence of Dengue virus (DENV) infection as defined by seroconversion to DENV
timeFrame: Year 1 through Year 5
measure: Incidence of Dengue virus (DENV) infection is defined by seroconversion
timeFrame: Year 1 through Year 5
measure: Incidence of Flavivirus (FLAV) infection as defined by seroconversion to FLAV
timeFrame: Year 1 through Year 5
measure: Incidence of Zika virus (ZIKV) infection is defined as seroconversion to ZIKV
timeFrame: Year 1 through Year 5
measure: Incident Arbovirus (ARBV) infections, as defined by seroconversion to Flavivirus (FLAV)
timeFrame: Year 1 through Year 5
Other outcomes:
Locations:
city: Belo Horizonte
country: Brazil
facility: Universidade Federal de Minas Gerais, Instituto de Ciencias Biologicas, Department of Biochemistry and Immunology
state: Minas Gerais
Study officials:
References:
citation: 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.