TY - JOUR
T1 - EVITA Dengue
T2 - a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil
AU - Collins, Matthew H.
AU - Potter, Gail E.
AU - Hitchings, Matt D.T.
AU - Butler, Ellie
AU - Wiles, Michelle
AU - Kennedy, Jessie K.
AU - Pinto, Sofia B.
AU - Teixeira, Adla B.M.
AU - Casanovas-Massana, Arnau
AU - Rouphael, Nadine G.
AU - Deye, Gregory A.
AU - Simmons, Cameron P.
AU - Moreira, Luciano A.
AU - Nogueira, Mauricio L.
AU - Cummings, Derek A.T.
AU - Ko, Albert I.
AU - Teixeira, Mauro M.
AU - Edupuganti, Srilatha
N1 - 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.
Funding Information:
The trial is funded by the US National Institutes of Health (Division of Microbiology and Infectious Diseases), the City of Belo Horizonte, and Brazilian Ministry of Health. As per the US-based regulatory requirements (Guidance for Industry #236 – Clarification of Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) Jurisdiction over Mosquito-Related Products) for mosquito-related products intended to cure, mitigate, treat, or prevent a disease (including by an intent to reduce the level, replication, or transmissibility of a pathogen in mosquitoes), are considered “drugs” under the Federal Food, Drug, & Cosmetic Act. However, the Wolbachia-infected mosquitoes will be neither manufactured nor deployed in the USA. Therefore, FDA oversight is not required in this trial.
Funding Information:
The authors thank Marcus Vin?cius Guimar?es de Lacerda, Amy Morrison, Kathryn Colborn, Tom Scott, and Elizabeth Halloran for valuable discussion and feedback on the trial design and operational considerations. We thank Dean Kleinhenz for supporting operations affiliated with this project. We thank the Hope Clinic of the Emory Vaccine Center and all members of the Emory Vaccine and Treatment Evaluation Unit and the Collins Laboratory who made the development of this protocol possible. We thank all members of the World Mosquito Program (WMP)-Brazil and WMP-Global teams who have contributed to the planning and implementation of the EVITA Dengue trial.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Arbovirus
KW - Chikungunya
KW - Clinical trial
KW - Cluster-randomized controlled trial
KW - Dengue
KW - Prevention
KW - Vector control
KW - Vector-borne disease
KW - Wolbachia
KW - Zika
UR - http://www.scopus.com/inward/record.url?scp=85125612029&partnerID=8YFLogxK
U2 - 10.1186/s13063-022-05997-4
DO - 10.1186/s13063-022-05997-4
M3 - Article
C2 - 35236394
AN - SCOPUS:85125612029
SN - 1745-6215
VL - 23
JO - Trials
JF - Trials
IS - 1
M1 - 185
ER -
