Model-based analysis of experimental hut data elucidates multifaceted effects of a volatile chemical on Aedes aegypti mosquitoes

Background. 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 movement of affected mosquitoes or volatile particles of the product beyond the treated house. Here, we propose a statistical inference framework for estimating these nuanced effects of volatile SRs. Methods. We fitted a continuous-time Markov chain model in a Bayesian framework to mark-release-recapture (MRR) data from an experimental hut study 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 downstream adjacent huts. We validated the framework using simulated data. Results. The odds of a female Ae. aegypti being repelled from 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 as far as 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). Conclusions. Our statistical inference framework is effective at elucidating multiple effects of volatile chemicals used in SR products, as well as their downstream effects. This framework provides a powerful tool for early selection of candidate SR product formulations worth advancing to costlier epidemiological trials, which are ultimately necessary for proof of concept of public health value and subsequent formal endorsement by health authorities.