Preventing malaria transmission: It's all in the smell

The ENAROMATIC study focused on identifying compounds with mosquito repellent properties. The idea was to interfere with the mosquito''s olfactory system as a means of preventing it from biting a human host, an essential step in malaria transmission.

Malaria is the prime example of a lethal disease carried by blood-feeding insects. It is caused by the parasite Plasmodium falciparum, which is transmitted to humans by female anopheline mosquitoes, particularly those of the genus Anopheles gambiae, during blood feeding.

Current malaria control measures usually try to inhibit the interaction between the insect vector and humans through the use of insecticides. However, these are toxic and their prolonged use is hampered by the emergence of resistance.

The EU-funded ''European network for advanced research on olfaction for malaria transmitting insect control'' (ENAROMATIC) project proposed to address this issue by interfering with the initial stages of odour recognition in anopheline mosquitoes. The goal was to study the mechanisms that underlie the specificity of the mosquito olfactory system and identify compounds that could inhibit the mosquito''s capacity to recognise a human host.

Since the olfactory process requires the coordinated action of odorant binding proteins (OBPs) and odorant receptors (ORs) to perceive odour stimuli, the ENAROMATIC consortium decided to manipulate both of these components. To this end, partners cloned several OBPs and Ors and expressed them in insect cells for the screening of synthetic and natural compounds.

Essential oils and constituent compounds emerged as candidates for triggering changes in female mosquito behaviour as determined by in vivo behavioural and electrophysiological assays. Furthermore, scientists determined the three-dimensional (3D) structure of OBPs in order to model the ligand OBP interaction, and design derivatives with better OBP binding properties. Tests employing some of the newly discovered mosquito repellents were undertaken in an African village where the mosquito vector and malaria are endemic. The tests revealed that at least one of the natural repellents repelled mosquitoes from dwellings as effectively as DEET, while mixtures of two or three of these repellents at the same total concentrations as DEET appear to be more effective than the latter.

the efficacy and minimal neurotoxicity of these compounds urged partners to search for additional natural anti-repellent compounds as a more environmentally safe option. Overall, the ENAROMATIC approach constitutes a novel strategy for preventing malaria transmission by disruption of the mosquito olfactory system. Commercial exploitation of the identified compounds could prove beneficial for those countries afflicted by malaria.

Related link:
http://cordis.europa.eu