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Table 2 Objectives, outcome measures, and endpoints

From: 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

Primary objective, outcome measure, and endpoint
Objective Outcome measure Endpoint
1. To evaluate whether the 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. Incident ARBV infection is defined as seroconversion to DENV, ZIKV, or CHIKV, as detected during annual serological evaluations. Seroconversion, defined as an initial negative titer (< 1:20) and subsequent titer ≥1:20 in FRNT50 testing of sequential annual samples OR ≥ fourfold increase in titer in FRNT50 testing of sequential annual samples with one or more FLAV (DENV1, DENV2, DENV3, DENV4, or ZIKV). Seroconversion for CHIKV, defined as IgG ELISA initial conversion from negative to positive. Seronegative is defined as FRNT50 < 1:20 for FLAV and IgG ELISA negative for CHIKV.
Secondary objectives, outcome measures, and endpoints
Objective Outcome measure Endpoint
1. To evaluate whether the release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence rate of ARBV infection, inferred from a model-based reconstruction of serological dynamics compared to standard Aedes vector control measures alone. ARBV infections, specifically due to FLAV or CHIKV, as detected during annual serological evaluations, inferred from a model-based reconstruction of serological dynamics. Model estimated infection based on the reconstruction of serological dynamics.
2. To evaluate whether the release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of FLAV or CHIKV infection among individuals who are seronegative to each of these families of viruses, respectively, at study entry, compared to standard Aedes vector control measures alone. Sero-incidence of FLAV or CHIKV infection as detected during annual serological evaluations in the sub-group of participants who are seronegative to each of these families of viruses, respectively. Seroconversion will be measured for the subgroup of participants who are ARBV seronegative (FRNT50 < 1:20 for FLAV or IgG ELISA negative for CHIKV) at study entry.
3. To evaluate whether the release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the overall sero-incidence of FLAV (DENV + ZIKV) infection. FLAV infection as detected during annual serological evaluations. Seroconversion, defined as an initial negative titer (< 1:20) and subsequent titer ≥1:20 in FRNT50 testing of sequential annual samples OR ≥ fourfold increase in FRNT50 titer of sequential annual samples with one or more FLAV (DENV1, DENV2, DENV3, DENV4, and ZIKV).
4. To evaluate whether the release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of DENV infection. DENV infection as detected during annual serological evaluations. Seroconversion, defined as an initial negative titer (< 1:20) and subsequent titer ≥1:20 in FRNT50 testing of sequential annual samples OR ≥ fourfold increase in FRNT50 titer of sequential annual samples with one or more DENV serotypes; AND ZIKV FRNT50 titer does NOT increase ≥ fourfold.
5. To evaluate whether the release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of ZIKV infection. ZIKV infection as detected during annual serological evaluations. Seroconversion, defined as an initial negative titer (< 1:20) and subsequent titer ≥1:20 in FRNT50 testing of sequential annual samples OR ≥ fourfold increase in FRNT50 titer of sequential annual samples with ZIKV; AND FRNT50 titer does NOT increase ≥ fourfold for any DENV serotype.
6. To evaluate whether the release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of CHIKV infection. CHIKV infection as detected during annual serological evaluations. Seroconversion for CHIKV, defined as IgG ELISA initial conversion from negative to positive.
7. To evaluate whether the release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of infection with a DENV serotype among individuals who are seropositive to another DENV serotype(s) at study entry, compared to standard Aedes vector control measures alone. Infection with a DENV serotype as detected during annual serological evaluations of the sub-group of participants who are seropositive to another DENV serotype(s). Infection with a new DENV serotype for the subgroup of participants who are seropositive (≥1:20) to a different DENV serotype(s) at study entry.
8. To evaluate the extent to which Wolbachia-infected Aedes aegypti mosquitoes replace uninfected adult Aedes aegypti in intervention clusters. Proportion of Wolbachia-infected Aedes aegypti adults in intervention clusters at specified time points Proportion of Wolbachia-infected (PCR-positive) Aedes aegypti adults in intervention clusters.
9. To evaluate the contamination of control clusters by Wolbachia-infected Aedes aegypti mosquitoes released in intervention clusters. Proportion of Wolbachia-infected Aedes aegypti adults in control clusters at specified time points. Proportion of Wolbachia-infected (PCR-positive) Aedes aegypti adults in control clusters.