Efficacy of a spatial repellent for control of Aedes -borne virus transmission: A cluster-randomized trial in Iquitos, Peru

Abstract

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 (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are 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 ABVs 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% (one-sided 95% CI lower limit, 6.9%; one-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 conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Use of mobile data collection systems within large-scale epidemiological field trials: findings and lessons-learned from a vector control trial in Iquitos, Peru

“…This individual used the IM-app to determine and record the number of intervention units applied inside each house at initial deployment [based on manufacturer specifications of target density (one unit per 9 m 2 )] and record the timing of intervention deployment, replacement, or removal (Table 1 ). The SM-team included 35 nurse-technicians, each with a mobile device, who used the SM-app to record census updates from 4039 houses and outcomes from routine subject febrile illness surveillance to identify potential dengue or Zika virus infection [ 37 ]. Both the IM and SM teams were responsible for reporting indicators of potential adverse events in subjects and family members of enrolled houses.…”

“…Here we describe the development, implementation and lessons learned from the use of a MDC system in a phase III randomized-cluster, placebo-controlled clinical trial evaluating the efficacy of a SR to reduce human infection with Aedes -borne viruses in the urban setting of Iquitos, Peru [ 20 ]. The overarching aim is to inform health stakeholders (investigators, funders, industries, health authorities) of the challenges and advantages of implementing MDC systems in similar field trials.…”

A cluster randomized, placebo control trial to evaluate the efficacy of a spatial repellent (Mosquito ShieldTM) against Aedes-borne virus infection among children ≥ 4–16 years of age in the Gampaha District, Sri Lanka: study protocol (the AEGIS program)

“…Based on previous SR trial, an effect size of 30% is conservative. [4] More informative for sample size calculations, the coefficient of variation in that trial was estimated following Hayes and Moulton to be 0.021. This was a low coefficient of variation, so for purposes of these sample size calculations, we assume the coefficient of variation is 0.15.…”

“…A recent study in Iquitos, Peru demonstrated a significant protective effect of a SR product against Aedesborne virus (ABV) transmission with a statistically significant reduction in the density of indoor female Aedes aegypti mosquitoes. [4] The use of a SR to demonstrate a reduction in ABV transmission has not been evaluated at large-scale in Asia. If effective, it could enhance vector control practices in the region and/or worldwide by complementing current disease prevention strategies.…”

“…aegypti female indoor abundance (28%) and blood-fed rate (12%) compared to baseline. [4] A proof-of-principle study in Sumba Island, Indonesia showed that communities (village clusters) with high coverage (90%) of a metofluthrin mosquito coil had 60% reduced malaria transmission and had lower biting pressure from anopheline vector mosquitoes.…”