Co-Toxicity Factor Analysis Reveals Numerous Plant Essential Oils Are Synergists of Natural Pyrethrins against Aedes aegypti Mosquitoes

SIMPLE SUMMARY: With insecticide-resistant mosquito populations becoming an ever-growing concern, new vector control technologies are needed. Plant essential oils represent new insecticides and repellents, which are generally safer to mammals and non-target organisms than conventional materials. A set of 20 plant essential oils was screened alone and in combination with a natural insecticide, pyrethrins, for their ability to produce immobilization (knockdown at 1 h) and mortality at 24 h against the yellow fever mosquito. Overall, only a few of the oils produced considerable mortality or knockdown when applied alone at the doses used in this study. However, a number of them synergized or antagonized the toxicity of natural pyrethrins when applied in mixtures. These findings highlight select plant essential oils that may offer important avenues for the development of future insecticide synergists. Moreover, synergism or antagonism was highly dependent on the amount of the oil applied, e.g., some oils were more effective at improving natural pyrethrins toxicity at low doses, whereas others were better at improving its toxicity at high doses. ABSTRACT: With insecticide-resistant mosquito populations becoming an ever-growing concern, new vector control technologies are needed. With the lack of new chemical classes of insecticides to control mosquito populations, the development of novel synergists may improve the performance of available insecticides. We screened a set of 20 plant essential oils alone and in combination with natural pyrethrins against Aedes aegypti (Orlando) female adult mosquitoes to assess their ability to synergize this natural insecticide. A co-toxicity factor analysis was used to identify whether plant oils modulated the toxicity of natural pyrethrins antagonistically, additively, or synergistically. Both knockdown at 1 h and mortality at 24 h were monitored. A majority of oils increased the toxicity of natural pyrethrins, either via an additive or synergistic profile. Many oils produced synergism at 2 µg/insect, whereas others were synergistic only at the higher dose of 10 µg/insect. Amyris, cardamom, cedarwood, and nutmeg East Indies (E.I.) oils were the most active oils for increasing the mortality of natural pyrethrins at 24 h with co-toxicity factors greater than 50 at either or both doses. A number of oils also synergized the 1 h knockdown of natural pyrethrins. Of these, fir needle oil and cypress oils were the most successful at improving the speed-of-action of natural pyrethrins at both doses, with co-toxicity factors of 130 and 62, respectively. To further assess the co-toxicity factor method, we applied selected plant essential oils with variable doses of natural pyrethrins to calculate synergism ratios. Only the oils that produced synergistic co-toxicity factors produced statistically significant synergism ratios. This analysis demonstrated that the degree of co-toxicity factor correlated well with the degree of synergism ratio observed (Pearson correlation coefficient r = 0.94 at 2 µg/insect; r = 0.64 at 10 µg/insect) and that the co-toxicity factor is a useful tool in screening for synergistic activity.