Abstract
BACKGROUND: The bites from infected female Anopheles mosquitoes lead to hundreds of thousands of deaths annually. To find a human, mosquitoes rely on their keen sense of smell. Repellents are chemicals that can target a mosquito's chemosensory senses. Therefore, targeting olfaction using repellents can be an effective way to prevent their attraction to humans and subsequent biting. However, the precise mechanisms underlying the mode of action for most commonly used repellents is surprisingly not well known. Recent evidence suggests that commonly used insect repellents target Anopheles mosquitoes by either activating mosquito olfactory neurons to trigger aversive responses or masking natural attractant cues emitted by the host to reduce attraction. METHODS: In this study, we used a combination of olfactory behavioral assays, calcium imaging of antennal neurons, and volatile organic compounds measurement in Anopheles mosquitoes to determine the specific mechanism by which one commercial repellent might outperform another. In our experiments, we assessed commercial products containing synthetic (DEET, IR3535, picaridin) or natural (p-menthane-3,8-diol, essential oils) ingredients. RESULTS: We found that natural products performed better than synthetic repellents on rapid odor-based repellency assays. On odor-based assays that allowed for longer time periods and odor accumulation, both products performed well, with p-methane-3,8-diol products showing consistent performance in both odor-based assays. Synthetic products demonstrated longer-lasting odor concentrations compared to more volatile natural products. The antennal olfactory neuron responses demonstrated clear differences between the two categories. We found that for Anopheles mosquitoes, the most effective products often combined masking and odor repellency, activated a number of antennal neurons, and evaporated at a slow rate. CONCLUSIONS: This approach provides insights into rational development of more effective Anopheles vector controls. Understanding the influence by which different mechanisms contribute to a repellent's function can improve vector control strategies for malaria-endemic regions.