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

• Type of Material: Article
• Authors: Nadine Rouphael, Emory University; Matthew Collins, Emory University; Gail E Potter, National Institutes of Health, Rockville; Matt DT Hitchings, University of Florida; Ellie Butler, Emory University; Michelle Wiles, Emory University; Jessie K Kennedy, The Emmes Company, LLC; Sofia B Pinto, Monash University; Adla BM Teixeira, Universidade Federal de Minas Gerais (UFMG); Arnau Casanovas-Massana, Yale School of Public Health; Gregory A Deye, National Institute of Allergy and Infectious Diseases; Cameron P Simmons, Monash University; Luciano A Moreira, Instituto René Rachou, Fiocruz, Belo Horizonte; Mauricio L Nogueira, Medical School of São Jose do Rio Preto FAMERP; Derek AT Cummings, University of Florida; Albert Ko, Yale School of Public Health, New Haven; Mauro M Teixeira, Federal University of Minas Gerais, Belo Horizonte; Srilatha Edupuganti, Emory University
• Language: English
• Date: 2022-03-02
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13063-022-05997-4
• Title of Journal or Parent Work: TRIALS
• Volume: 23
• Issue: 1
• Start Page: 185
• End Page: 185
• Grant/Funding Information: This study is funded by the National Institutes of Health, National Institute of Allergy and Infectious Disease, Division of Microbiology and Infectious Diseases via the Vaccine and Treatment Evaluation Unit program (DMID17-0111, Contracts HHSN272201300018I/HHSN27200018-FY.2018.A1B1C1D1.0077). Emmes work for this study is supported by contract 75N93021C00012. Additional funding is provided by the Brazilian Ministry of Health, the City of Belo Horizonte, and the World Mosquito Program.
• Keywords: Wolbachia; TRANSMISSION; Medicine, Research & Experimental; Research & Experimental Medicine; Zika; Life Sciences & Biomedicine; Dengue; Prevention; CHIKUNGUNYA; KNOWLEDGE; Arbovirus; ZIKA VIRUS; Chikungunya; EPIDEMIOLOGY; Science & Technology; Clinical trial; Cluster-randomized controlled trial; Vector-borne disease; Vector control
• Research Categories: Biology, Microbiology; Biology, Biostatistics; Health Sciences, Epidemiology

Abstract

Background: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. Methods: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6–11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. Discussion: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. Trial registration: ClinicalTrials.govNCT04514107. Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.