Background: Studying the behavioral response of blood-sucking disease-vector insects to potentially repellent volatile compounds could shed light on the development of new control strategies. Volatiles released by human facial skin microbiota play different roles in the host-seeking behavior of triatomines. We assessed the repellency effect of such compounds of bacterial origin on Triatoma infestans and Rhodnius prolixus, two important vectors of Chagas disease in Latin America. Methods: Using an exposure device, insects were presented to human odor alone (control) and in the presence of three individual test compounds (2-mercaptoethanol, dimethyl sulfide and 2-phenylethanol, the latter only tested in R. prolixus) and the gold-standard repellent NN-diethyl-3-methylbenzamide (DEET). We quantified the time the insects spent in the proximity of the host and determined if any of the compounds evaluated affected the behavior of the insects. Results: We found volatiles that significantly reduced the time spent in the proximity of the host. These were 2-phenylethanol and 2-mercaptoethanol for R. prolixus, and dimethyl sulfide and 2-mercaptoethanol for T. infestans. Such an effect was also observed in both species when DEET was presented, although only at the higher doses tested. Conclusions: The new repellents modulated the behavior of two Chagas disease vectors belonging to two different triatomine tribes, and this was achieved using a dose up to three orders of magnitude lower than that needed to evoke the same effect with DEET. Future efforts in understanding the mechanism of action of repellent compounds such as 2-mercaptoethanol, as well as an assessment of their temporal and spatial repellent properties, could lead to the development of novel control strategies for these insect vectors, refractory to DEET.

24 25 Background: Studying the behavioral response of blood-sucking, disease-vector insects to 26 potentially repellent volatile compounds could shed light on the development of new 27 control strategies. Volatiles released by human facial skin microbiota play different roles in 28 the host-seeking behavior of triatomines. We assessed the repellency effect of such 29 compounds of bacterial origin on Triatoma infestans and Rhodnius prolixus, two important 30 vectors of Chagas disease in Latin America. 31 Methods: Using an exposure device, insects were presented to human odor alone (negative 32 control) and in the presence of three individual tested compounds (2-mercaptoethanol, 33 dimethyl sulfide and 2-phenylethanol, which was only tested in R. prolixus) and the gold-34 standard repellent NN-diethyl-3-methylbenzamide-DEET (positive control). We quantified 35 the time the insects spent in the proximity of the host and performed nonparametric 36 statistical tests to determine if any of the compounds evaluated affected the behavior of the 37 insect. 38Results: We found volatiles that significantly reduced the time spent in the proximity of the 39 host. These were 2-phenylethanol and 2-mercaptoethanol for R. prolixus, and dimethyl 40 sulfide and 2-mercaptoethanol for T. infestans. Such an effect was also observed in both 41 species when DEET was presented, although only at the higher doses tested. 42 Conclusions:The new repellents modulated the behavior of two Chagas disease vectors 43 belonging to two different triatomine tribes, and this was achieved using a dose up to three 44 orders of magnitude lower than that needed to evoke the same effect with DEET. Future 45 efforts in understanding deeply the mechanism of action of repellent compounds such as 2-46 3 mercaptoethanol, as well as an assessment of their temporal and spatial repellent properties, 47 could lead to the development of novel control strategies for insect vectors refractory to 48 DEET. 49