Cédric Pennetier

Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

BackgroundN,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system.ResultsBy using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase.ConclusionThese findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.

Managing insecticide resistance in malaria vectors by combining carbamate-treated plastic wall sheeting and pyrethroid-treated bed nets

BackgroundPyrethroid resistance is now widespread in Anopheles gambiae, the major vector for malaria in sub-Saharan Africa. This resistance may compromise malaria vector control strategies that are currently in use in endemic areas. In this context, a new tool for management of resistant mosquitoes based on the combination of a pyrethroid-treated bed net and carbamate-treated plastic sheeting was developed.MethodsIn the laboratory, the insecticidal activity and wash resistance of four carbamate-treated materials: a cotton/polyester blend, a polyvinyl chloride tarpaulin, a cotton/polyester blend covered on one side with polyurethane, and a mesh of polypropylene fibres was tested. These materials were treated with bendiocarb at 100 mg/m2 and 200 mg/m2 with and without a binding resin to find the best combination for field studies. Secondly, experimental hut trials were performed in southern Benin to test the efficacy of the combined use of a pyrethroid-treated bed net and the carbamate-treated material that was the most wash-resistant against wild populations of pyrethroid-resistant An. gambiae and Culex quinquefasciatus.ResultsMaterial made of polypropylene mesh (PPW) provided the best wash resistance (up to 10 washes), regardless of the insecticide dose, the type of washing, or the presence or absence of the binding resin. The experimental hut trial showed that the combination of carbamate-treated PPW and a pyrethroid-treated bed net was extremely effective in terms of mortality and inhibition of blood feeding of pyrethroid-resistant An. gambiae. This efficacy was found to be proportional to the total surface of the walls. This combination showed a moderate effect against wild populations of Cx. quinquefasciatus, which were strongly resistant to pyrethroid.ConclusionThese preliminary results should be confirmed, including evaluation of entomological, parasitological, and clinical parameters. Selective pressure on resistance mechanisms within the vector population, effects on other pest insects, and the acceptability of this management strategy in the community also need to be evaluated.

Mixture for controlling insecticide-resistant malaria vectors

Impregnating mosquito nets with an insect repellent and a low dose of organophosphorous insecticide combination was effective.

Remote effect of insecticide-treated nets and the personal protection against malaria mosquito bites

Experimental huts are part of the WHO process for testing and evaluation of Insecticide Treated Nets (ITN) in semi-field conditions. Experimental Hut Trials (EHTs) mostly focus on two main indicators (i.e., mortality and blood feeding reduction) that serve as efficacy criteria to obtain WHO interim recommendation. However, several other outputs that rely on counts of vectors collected in the huts are neglected although they can give useful information about vectors’ behavior and personal protection provided by ITNs. In particular, EHTs allow to measure the deterrent effect and personal protection of ITNs. To provide a better assessment of ITNs efficacy, we performed a retrospective analysis of the deterrence and the personal protection against malaria transmission for 12 unwashed and 13 washed ITNs evaluated through EHTs conducted in West Africa. A significant deterrent effect was shown for six of the 12 unwashed ITNs tested. When washed 20 times, only three ITNs had significant deterrent effect (Rate Ratios (RR)<1; p<0.05) and three showed an apparent “attractiveness” (RR>1; p<0.01). When compared to the untreated net, all unwashed ITNs showed lower number of blood-fed Anopheles indicating a significant personal protection (RR<1, p<0.05). However, when washed 20 times, three ITNs that were found to be attractive did not significantly reduce human-vector contact (p>0.05). Current WHO efficacy criteria do not sufficiently take into account the deterrence effect of ITNs. Moreover, the deterrence variability is rarely discussed in EHT’s reports. Our findings highlighted the long-range effect (deterrent or attractive) of ITNs that may have significant consequences for personal/community protection against malaria transmission. Indicators measuring the deterrence should be further considered for the evaluation of ITNs.

Influence of pyrethroïd-treated bed net on host seeking behavior of Anopheles gambiae s.s. carrying the kdr allele

The use of long lasting insecticide nets (LLINs) treated with pyrethroïd is known for its major contribution in malaria control. However, LLINs are suspected to induce behavioral changes in malaria vectors, which may in turn drastically affect their efficacy against Plasmodium sp. transmission. In sub Saharan Africa, where malaria imposes the heaviest burden, the main malaria vectors are widely resistant to pyrethroïds, the insecticide family used on LLINs, which also threatens LLIN efficiency. There is therefore a crucial need for deciphering how insecticide-impregnated materials might affect the host-seeking behavior of malaria vectors in regards to insecticide resistance. In this study, we explored the impact of permethrin-impregnated net on the host attractiveness for Anopheles gambiae mosquitoes, either susceptible to insecticides, or carrying the insecticide resistance conferring allele kdr. Groups of female mosquitoes were released in a dual-choice olfactometer and their movements towards an attractive odor source (a rabbit) protected by insecticide-treated (ITN) or untreated nets (UTN) were monitored. Kdr homozygous mosquitoes, resistant to insecticides, were more attracted by a host behind an ITN than an UTN, while the presence of insecticide on the net did not affect the choice of susceptible mosquitoes. These results suggest that permethrin-impregnated net is detectable by malaria vectors and that the kdr mutation impacts their response to a LLIN protected host. We discuss the implication of these results for malaria vector control.