Efficacy of a Spatial Repellent for Control of Aedes-Borne Virus Transmission: A Cluster Randomized Trial in Iquitos, Peru
Authors: Morrison Amy C. , Reiner Robert C. , Elson William H. , Astete Helvio , Guevara Carolina , del Aguila Clara , Bazan Isabel , Siles Crystyan , Barrera Patricia , Kawiecki Anna B. , Barker Christopher M. , Vasquez Gissella M. , Escobedo-Vargas Karin , Flores-Mendoza Carmen , Huaman Alfredo A. , Leguia Mariana , Silva Maria E. , Jenkins Sarah A. , Campbell Wesley R. , Abente Eugenio J. , Hontz Robert D. , Paz-Soldan Valerie A. , Grieco John P. , Lobo Neil F. , Scott Thomas W. , Achee Nicole L. 
Published: March 2021

Over half the world’s population is at risk for viruses transmitted by Aedes mosquitoes, such as, dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABV) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases is limited to Wolbachia in a single trial in Indonesia, and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABV by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate and parity status through mixed effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34·1% (1-sided 95% CI lower limit, 6·9%; 1-sided p-value=0·0236, z=1·98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28·6% (95% CI 24·1%, ∞); z=-9·11) and 12·4% (95% CI 4·2%, ∞); z=-2·43), respectively. Our trial provides the first conclusive statistical evidence from a pre-planned cluster randomized controlled clinical trial with a pre-defined effect size on the primary endpoint that was appropriate powered to prospectively quantify and statistically test for a difference in the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Significance Statement

Vector interventions are needed for Aedes-borne viral diseases (dengue, Zika, chikungunya, and yellow fever) prevention, but their application is hindered by the lack of evidence proving they prevent infection or disease. Our research reports the first conclusive statistical evidence from a pre-planned, prospective cluster-randomized, controlled clinical trial (cRCT) of significant protective efficacy (34.1% hazard estimate) against human Aedes-borne virus (ABV) infection by a chemical-based vector control intervention, the most commonly used intervention category among all ABV World Health Organization recommendations. A previous trial against malaria in Indonesia indicated a positive trend but did not detect a significant effect. Results from our ABV study will help guide public health authorities responsible for operational management and world-wide prevention of ABV, and incentivize new strategies for disease prevention.