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Title:   Author  item
                                            ALI, ABBAS - University Of Mississippiitem
                                            Cantrell, Charlesitem
                                            Bernier, Ulrichitem
                                            Duke, Stephenitem
                                            SCHNEIDER, JOHN - Mississippi State Universityitem
                                            Agramonte, Natashaitem
                                            KHAN, IKLAS - University Of Mississippi
  Submitted to: Journal of Medical Entomology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 8/11/2012
                                    Publication  Date: 11/1/2012
                                    Citation: Ali, A., Cantrell, C.L., Bernier, U.R., Duke, S.O., Schneider, J.C., Agramonte, N.M., Khan, I. 2012. Aedes aegypti (Diptera: culicidae) biting deterrence: structure-activity relationship of saturated and unsaturated fatty acids. Journal of Medical Entomology. 49:1370-1378.Interpretive Summary: Mosquitoes transmit many serious human diseases including malaria, Japanese encephalitis, yellow fever, dengue and filariasis.  Aedes aegypti (L) carries arboviruses, which cause dengue fever in human beings; and 40% of the world population is considered to be at risk.  Chemicals derived from plants offer potential alternatives to synthetic mosquito management chemicals.  Plant products are potential weapons in future mosquito management programs, as some function as insecticides, growth and reproductive inhibitors, repellents and deterrents.  In this study we systematically evaluated for the first time the biting deterrent effects of a series of saturated and unsaturated fatty acids against Aedes aegypti [yellow fever mosquito (Diptera: Culicidae)] using the K & D bioassay system.  Among the saturated fatty acids, mid chain length acids (C10:0 to C13:0) showed the highest biting deterrent activity against Ae. aegypti as compared to short chain length acids (C6: to C9:0) and long chain length acids (C14:0 to C18:0).  Among the unsaturated fatty acids, C11:1 showed the highest activity with biting deterrent effect statistically equivalent to DEET.   All the fatty acids (C11:0, C12:0, C11:1 and C12:1) and DEET showed significantly higher activity at all test intervals than the solvent control.  Longevity and dose-response studies suggested that all four fatty acids are good candidates for commercial insect repellent development studies.
                                Technical Abstract: In this study we systematically evaluated for the first time the biting deterrent effects of a series of saturated and unsaturated fatty acids against Aedes aegypti [yellow fever mosquito (Diptera: Culicidae)] using the K & D bioassay system (Klun et al 2005).  The saturated fatty acids (C6:0 to C16:0 and C18:0) and unsaturated fatty acids (C11:1 to C14:1, C16:1, C18:1 and C18:2) showed Biting Deterrence Index (BDI) values significantly greater than ethanol, the negative control.  Among the saturated fatty acids, mid chain length acids (C10:0 to C13:0) showed the highest biting deterrent activity against Ae. aegypti as compared to short chain length acids (C6: to C9:0) and long chain length acids (C14:0 to C18:0) except C8:0 and C16:0 where the activity was significantly higher than the other short and long chain acids.  Mid chain length acids (C10:0 to C13:0) showed BDI values not significantly less than N, N-diethyl-meta-toluamide (DEET), the positive control at 25 nmol/cm2.  Among the unsaturated fatty acids, C11:1 showed the highest activity (BDI = 1.05) and C18:2 had the lowest activity (BDI=0.7).  C11:1, C12:1 and C14:1 showed BDI values not significantly less than DEET.   Following the preliminary observations, residual activity and dose response studies were performed on C11, C12, C11:1 and C12:1 over a 24-h period at 25 nmol/cm2.  All the fatty acids (C11:0, C12:0, C11:1 and C12:1) and DEET showed significantly higher activity at all test intervals than the solvent control.  At treatment and 1-h post treatment, all fatty acids showed Proportion Not Biting (PNB) values not significantly less than DEET.  At 3-, 6- and 12-h post treatment, all fatty acids showed PNB values significantly greater than DEET.  At 24-h post treatment, only the PNB value for C12:0 was significantly higher than DEET.  The dose-responses of C12:0 and DEET were determined at concentrations of 25 to 5 nmol/cm2.  As in the residual activity bioassays, the PNB values for C12:0 and DEET at 25 nmol/cm2 were not significantly different.  However, at lower concentrations, the PNB values for C12:0 were significantly greater than DEET.  These results clearly indicate that mid chain length fatty acids not only possess levels of biting deterrence similar to DEET at 25 nmol/cm2 but also have better residual activity than DEET.  In contrast, the in vivo, treated cloth patch assay system (Katritzky et al. 2010) showed that the mid chain length fatty acids C11:0, C11:1 C12:0 and C12:1 had Minimum Effective Dose (MED) values significantly greater than DEET against Ae. aegypti and that the relative repellent potency varied according to species tested.  MED values of C11:0 (81), C12:0 (95), and C11:1 (49) nmol/cm2 against Anopheles quadrimaculatus were almost as potent as DEET with a MED of 37 nmol/cm2 against this species. The MED ratio of C11:1 compared to DEET was 1.4 indicating this was the most potent repellent of the acids tested.  The C11 and C11:1 acids were more potent repellents (had lower MED values) for all three species of mosquitoes using the “cloth patch assay.”


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