Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

Int J Environ Res Public Health. 2017 Feb 6;14(2):154. doi: 10.3390/ijerph14020154.

Abstract

Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

Keywords: Aedes aegypti; Anopheles gambiae; Drosophila melanogaster; GABA receptor; fipronil.

MeSH terms

  • Aedes*
  • Animals
  • Anopheles*
  • Biomarkers / metabolism
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / metabolism
  • Insecticides* / pharmacology
  • Isoxazoles* / pharmacology
  • Larva / drug effects
  • Lethal Dose 50
  • Pyrazoles
  • Receptors, GABA / metabolism

Substances

  • A1443 compound
  • Biomarkers
  • Insecticides
  • Isoxazoles
  • Pyrazoles
  • Receptors, GABA
  • fipronil