The TIRS trial: protocol for a cluster randomized controlled trial assessing the efficacy of preventive targeted indoor residual spraying to reduce Aedes-borne viral illnesses in Merida, Mexico

• Type of Material: Article
• Authors: Pablo Manrique-Saide, Universidad Autonoma de Yucatan; Natalie Dean, Emory University; M. Elizabeth Halloran, Center for Inference and Dynamics of Infectious Diseases; Ira M. Longini, University of Florida; Matthew Collins, Emory University; Lance Waller, Emory University; Hector Gomez-Dantes, National Institute of Public Health; Audrey Lenhart, Centers for Disease Control and Prevention; Thomas J. Hladish, University of Florida; Azael Che-Mendoza, Universidad Autonoma de Yucatan; Oscar D. Kirstein, Emory University; Yamila Romer, Emory University; Fabian Correa-Morales, Centro Nacional de Programas Preventivos y Control de Enfermedades (CENAPRECE) Secretaría de Salud Mexico; Jorge Palacio-Vargas, Secretaria Salud de Yucatan; Rosa Mendez-Vales, Secretaria Salud de Yucatan; Pilar Granja Perez, Secretaria Salud de Yucatan; Norma Pavia-Ruz, Universidad Autonoma de Yucatan; Guadalupe Ayora-Talavera, Universidad Autonoma de Yucatan; Gonzalo Vazquez Prokopec, Emory University
• Language: English
• Date: 2020-10-08
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s). 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13063-020-04780-7
• Title of Journal or Parent Work: Trials
• Volume: 21
• Issue: 1
• Start Page: 839
• End Page: 839
• Grant/Funding Information: NIH/National Institute of Allergy and Infectious Disease (R01 AI139761; Dean, PI), and the Innovative Vector Control Consortium, IVCC (DFID:30041-105; Vazquez-Prokopec, PI).; Vazquez-Prokopec, PI) and partially by grants from NIH/National Institute of General Medical Sciences (U54 GM111274; Halloran, PI),; NIH/National Institute of Allergy and Infectious Disease (R37 AI0032042; Halloran, PI),; This study is funded by National Institutes of Health, National Institute of Allergy and Infectious Disease (U01AI148069
• Keywords: Yucatan; Life Sciences & Biomedicine; City; Insecticide; Research & Experimental Medicine; Indoor; Science & Technology; Dengue antibodies; Dengue; Medicine, Research & Experimental; Virus; Aedes aegypti; Populations; Chikungunya; Urban; Zika; Cluster randomized
• Research Categories: Biology, Biostatistics; Environmental Sciences; Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology

Abstract

Background Current urban vector control strategies have failed to contain dengue epidemics and to prevent the global expansion of Aedes-borne viruses (ABVs: dengue, chikungunya, Zika). Part of the challenge in sustaining effective ABV control emerges from the paucity of evidence regarding the epidemiological impact of any Aedes control method. A strategy for which there is limited epidemiological evidence is targeted indoor residual spraying (TIRS). TIRS is a modification of classic malaria indoor residual spraying that accounts for Aedes aegypti resting behavior by applying residual insecticides on exposed lower sections of walls (< 1.5 m), under furniture, and on dark surfaces. Methods/design We are pursuing a two-arm, parallel, unblinded, cluster randomized controlled trial to quantify the overall efficacy of TIRS in reducing the burden of laboratory-confirmed ABV clinical disease (primary endpoint). The trial will be conducted in the city of Merida, Yucatan State, Mexico (population ~ 1million), where we will prospectively follow 4600 children aged 2–15 years at enrollment, distributed in 50 clusters of 5 × 5 city blocks each. Clusters will be randomly allocated (n = 25 per arm) using covariate-constrained randomization. A “fried egg” design will be followed, in which all blocks of the 5 × 5 cluster receive the intervention, but all sampling to evaluate the epidemiological and entomological endpoints will occur in the “yolk,” the center 3 × 3 city blocks of each cluster. TIRS will be implemented as a preventive application (~ 1–2 months prior to the beginning of the ABV season). Active monitoring for symptomatic ABV illness will occur through weekly household visits and enhanced surveillance. Annual sero-surveys will be performed after each transmission season and entomological evaluations of Ae. aegypti indoor abundance and ABV infection rates monthly during the period of active surveillance. Epidemiological and entomological evaluation will continue for up to three transmission seasons. Discussion The findings from this study will provide robust epidemiological evidence of the efficacy of TIRS in reducing ABV illness and infection. If efficacious, TIRS could drive a paradigm shift in Aedes control by considering Ae. aegypti behavior to guide residual insecticide applications and changing deployment to preemptive control (rather than in response to symptomatic cases), two major enhancements to existing practice. Trial registration ClinicalTrials.gov NCT04343521. Registered on 13 April 2020. The protocol also complies with the WHO International Clinical Trials Registry Platform (ICTRP) (Additional file 1).