Field evaluation of a volatile pyrethroid spatial repellent and etofenprox-treated clothing for outdoor protection against forest malaria vectors in Cambodia

Abstract

Cambodias goal to eliminate malaria by 2025 is challenged by persisting transmission in the countrys forest and forest fringe areas. People living in, or traveling to the forest, are exposed to malaria vector bites during the day due to Anopheles daytime biting; and during the night, due to low bed net use and open sleeping structures. Volatile pyrethroid spatial repellents (VPSRs), and insecticide treated clothing (ITC) may help address these gaps in protection. In this field study the authors evaluated the outdoor application of one passive, transfluthrin-based VPSR, four etofenprox-ITCs paired with a picaridin topical repellent, and a combination of VPSR and ITC against wild Anopheles landing in Cambodia. Mathematical modeling was also used to predict the reduction of vectorial capacity of these interventions. A 7x7 Latin-square (6 interventions and one control) was conducted over 49 collection nights in seven temporary, open structures in a forest in Mondulkiri Province, Cambodia. Pairs of participants conducted human landing catches (HLCs) from 18h00 to 06h00, with each collector conducting collections for six hours. A randomly selected subset of collected Anopheles were identified to species using molecular methods. The rate ratio of each intervention compared to the control on Anopheles landings was estimated using a mixed-effect negative binomial regression with intervention, structure, and collector-pair as fixed-effects, and with collection date and structure-night as random effects. The modeling assessment aims to predict the relative reduction in vectoral capacity. Initial calculations involved establishing a "baseline scenario" without intervention, utilizing biometric parameters for Anopheles dirus. Various scenarios accounting for intervention coverage and adherence were then considered. The study aims to update parameters using field study estimates for wild Anopheles, incorporating multiple semi-field estimates for interventions and accounting for the variability and uncertainty in parameter values. Of the total 8,294 Anopheles specimens collected, 15% (n=1,242) of specimens were confirmed to species or species group via PCR. Fifteen species were confirmed; Anopheles dirus Form A was predominant (n=429), followed by Anopheles maculatus (n=189), and Anopheles minimus (n=60). All six interventions reduced Anopheles landing substantially; protective efficacies ranged between 61% (95% confidence interval (CI): 48 - 71%) (etofenprox-ITC, washed) and 95% (95% CI: 93 - 96%) (combined VPSR and unwashed etofenprox-ITC). Finally, the modelling assessment demonstrates significant reductions in vectoral capacity, with the highest impact observed for the combined ITC and VPSR as well as the VPSR used alone, although effectiveness decreases with intervention aging, and variability exists in the magnitude of predicted reductions due to differences in experimental conditions. These transfluthrin-based VPSR and etofenprox ITC interventions have the potential to reduce outdoor and daytime Anopheles biting by providing substantial protection against Anopheles landing. One or more of these tools may play a valuable role in the push for elimination in Cambodia and the Greater Mekong Subregion if programs can achieve effective coverage.