Model-based analysis of experimental data from interconnected, row-configured huts elucidates multifaceted effects of a volatile chemical on Aedes aegypti mosquitoes

Quirine A. ten Bosch, Fanny Castro-Llanos, Hortance Manda, Amy C. Morrison, John P. Grieco, Nicole L. Achee, T. Alex Perkins

Insecticides used against Aedes aegypti and other disease vectors can elicit a multitude of dose-dependent effects on behavioral and bionomic traits. Estimating the potential epidemiological impact of a product requires thorough understanding of these effects and their interplay at different dosages. Volatile spatial repellent (SR) products come with an additional layer of complexity due to the potential for altered movement of affected mosquitoes and diffusion of volatile particles of the product beyond the treated house. Here, we propose a paired experimental design and statistical inference framework for estimating these nuanced effects of volatile SRs. We fitted a continuous-time Markov chain model in a Bayesian framework to data on marked mosquitoes released in interconnected experimental huts conducted in Iquitos, Peru. We estimated the effects of two dosages of transfluthrin on Ae. aegypti behaviors associated with human-vector contact: repellency, exiting and knockdown in the treated space and in connected, adjacent huts. We validated the framework using simulated data. The odds of a female Ae. aegypti being repelled, and thus prevented from entering a treated hut (HT), increased at both dosages (low dosage: odds = 1.64, 95% highest density interval (HDI) = 1.30-2.09; high dosage: odds = 1.35, HDI = 1.04-1.67). The relative risk of exiting from the treated hut was reduced (low: RR = 0.70, HDI = 0.62-1.09; high: RR = 0.70, HDI = 0.40-1.06), with this effect carrying over to untreated spaces two huts away from the treated hut (H2) (low: RR = 0.79, HDI = 0.59-1.01; high: RR = 0.66, HDI = 0.50-0.87). Knockdown rates were increased in both treated and downstream huts, particularly under high dosage (HT: RR = 8.37, HDI = 2.11-17.35; H1: RR = 1.39, HDI = 0.52-2.69; H2: RR = 2.22, HDI = 0.96-3.86). Our framework is effective at elucidating multiple effects of volatile chemicals used in SR products, as well as their downstream effects. For the examined formulations of transfluthrin, we found notable dose-dependent effects on repellency, movement and knockdown that carry over to adjacent, untreated spaces.