Jean-Marc Hougard

The spread of the Leu-Phe kdr mutation through Anopheles gambiae complex in Burkina Faso: genetic introgression and de novo phenomena

During extensive sampling in Burkina Faso and other African countries, the Leu‐Phe mutation producing the kdr pyrethroid resistance phenotype was reported in both Anopheles gambiae ss and A. arabiensis. This mutation was widely distributed at high frequency in the molecular S form of A. gambiae while it has been observed at a very low frequency in both the molecular M form and A. arabiensis in Burkina Faso. While the mutation in the M form is inherited through an introgression from the S form, its occurrence is a new and independent mutation event in A. arabiensis. Three nucleotides in the upstream intron of the kdr mutation differentiated A. arabiensis from A. gambiae ss and these specific nucleotides were associated with kdr mutation in A. arabiensis. Ecological divergences which facilitated the spread of the kdr mutation within the complex of A. gambiae ss in West Africa, are discussed.

Dinotefuran: A Potential Neonicotinoid Insecticide Against Resistant Mosquitoes

Abstract Because pyrethroid, organophosphate, and carbamate resistance is more and more developed in mosquitoes of medical importance, there is an urgent need for alternative insecticides for vector control. Dinotefuran, a new neonicotinoid insecticide commercialized by Mitsui Chemicals (Tokyo, Japan), could be a useful candidate in public health because it shows low mammalian toxicity and great insecticidal activity against a broad range of pests. In this study, the intrinsic toxicity of dinotefuran was evaluated by larval bioassay and topical application against different mosquito strains of Anopheles gambiae Giles, Culex quinquefasciatus Say, and Aedes aegypti L. having none, one, or several resistance mechanisms, respectively, to insecticides. The results showed that dinotefuran was less toxic than most of the commonly used insecticides (e.g., deltamethrin, carbosulfan, and temephos) against the susceptible mosquitoes tested (between 6- and 100-fold at the LD50 level). However, the toxicity of dinotefuran was not strongly affected by the presence of common resistance mechanism, i.e., kdr mutation and insensitive acetylcholinesterase (resistance ratio [RR] from 1.3 to 2.3). More interestingly, the carbamate-resistant strain of Cx. quinquefasciatus was significantly more affected by dinotefuran than the susceptible strain (RR = 0.70), probably because the insensitive acetylcholinesterase is less efficient to degrade nicotinic substrates than normal acetylcholinesterase. Despite the relatively low toxicity of dinotefuran against susceptible mosquitoes, the absence of cross-resistance with common insecticides (pyrethroids, carbamates, and organophosphates) makes neonicotinoids potential candidates for disease vector control, especially in area where mosquitoes are resistant to insecticides.

Efficacy of mosquito nets treated with insecticide mixtures or mosaics against insecticide resistant Anopheles gambiae and Culex quinquefasciatus (Diptera: Culicidae) in Côte d'Ivoire.

Only pyrethroid insecticides have so far been recommended for the treatment of mosquito nets for malaria control. Increasing resistance of malaria vectors to pyrethroids threatens to reduce the potency of this important method of vector control. Among the strategies proposed for resistance management is to use a pyrethroid and a non-pyrethroid insecticide in combination on the same mosquito net, either separately or as a mixture. Mixtures are particularly promising if there is potentiation between the two insecticides as this would make it possible to lower the dosage of each, as has been demonstrated under laboratory conditions for a mixture of bifenthrin (pyrethroid) and carbosulfan (carbamate). The effect of these types of treatment were compared in experimental huts on wild populations of Anopheles gambiae Giles and the nuisance mosquito Culex quinquefasciatus Say, both of which are multi-resistant. Four treatments were evaluated in experimental huts over six months: the recommended dosage of 50 mg m(-2) bifenthrin, 300 mg m(-2) carbosulfan, a mosaic of 300 mg m(-2) carbosulfan on the ceiling and 50 mg m(-2) bifenthrin on the sides, and a mixture of 6.25 mg m(-2) carbosulfan and 25 mg m(-2) bifenthrin. The mixture and mosaic treatments did not differ significantly in effectiveness from carbosulfan and bifenthrin alone against anophelines in terms of deterrency, induced exophily, blood feeding inhibition and overall mortality, but were more effective than in earlier tests with deltamethrin. These results are considered encouraging, as the combination of different classes of insecticides might be a potential tool for resistance management. The mixture might have an advantage in terms of lower cost and toxicity.

Bifenthrin: A Useful Pyrethroid Insecticide for Treatment of Mosquito Nets

Abstract Bifenthrin, a pyrethroid insecticide already used in agriculture was evaluated in laboratory conditions against susceptible and pyrethroid resistant mosquitoes, as a potential insecticide for treatment of mosquito nets. Two laboratory strains of Anopheles gambiae s.s. Giles, the major malaria vector in Africa, and two of Culex quinquefasciatus Say, a major pest mosquito in urban areas, were used. Compared with other pyrethroids such as permethrin and deltamethrin, the intrinsic toxicity of bifenthrin, measured by topical application with susceptible strains, was intermediate. By forced tarsal contact on filter papers (cylinder tests) or on netting materials (cone tests), bifenthrin was found slightly more effective against A. gambiae than against C. quinquefasciatus, in terms of mortality and knock-down effect. With free flying mosquitoes (tunnel tests), bifenthrin was very efficient in killing mosquitoes and inhibiting blood feeding. Against the two pyrethroid resistant strains, bifenthrin was relatively efficient against A. gambiae but the impact of resistance was greater with C. quinquefasciatus. In tunnel tests, blood feeding remained almost entirely inhibited with the two species despite resistance. The high mortality of susceptible mosquitoes and excellent blood feeding inhibition of susceptible and resistant strains makes bifenthrin a good candidate for treatment of netting materials, particularly in areas where C. quinquefasciatus, the main nuisance in urban areas, is resistant to pyrethroids. The slower knock-down and lower irritant effect also makes this insecticide especially attractive when a mass killing effect on mosquito populations is expected.

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.

Lethal and behavioural effects of three synthetic repellents (DEET, IR3535 and KBR 3023) on Aedes aegypti mosquitoes in laboratory assays

Abstract The knock‐down, mortality and ‘irritancy’ effects of three synthetic repellents (DEET, IR3535 and KBR 3023) on Aedes aegypti (L) (Diptera: Culicidae) were evaluated in the laboratory in the absence of animal bait. Filter paper tests were carried out to assess the knock‐down effect (KDt50 and KDt95) and mortality (LC50 and LC95) induced by each repellent. ‘Irritancy’ tests were carried out to compare the flight response (time to first take‐off, or FT) to increasing concentrations of repellents (2–7%) and at five distances from the treated surface (0–40 mm). DEET had an insecticidal effect (KDt50= 9.7 min at 7%; CL50= 1165 mg/m2), whereas IR3535 and KBR 3023 did not. Relative to an untreated control, IR3535 was an irritant (relative irritancy or RI > 1) at doses of 5% and 7% (RI = 17.7 and 9.9, respectively), whereas DEET was an irritant at lower concentrations (RI = 12.3 at 2% DEET). KBR 3023 was the weakest irritant over the same range of concentrations (RImax= 3.6 at 6%). DEET was more of an irritant (RI20= 9.4) than IR3535 (RI20= 2.9) over a range of distances (0–20 mm), and KBR 3023 was not an irritant unless mosquitoes made contact with the treated surface. All three repellents had a significant effect on mosquitoes, but DEET exhibited a more complex mode of action than the others due to its insecticidal properties. The repellents do not behave as a single class of compounds with a common mode of action, but most probably affect different physiological systems in insects. The physiological and molecular mechanisms of repellents, especially DEET, should be investigated to ensure a better use of these molecules for skin applications and/or for treating materials against mosquitoes.

Eliminating Onchocerciasis after 14 Years of Vector Control: A Proved Strategy

From 1976 through 1989, weekly aerial spraying operations against blackflies were carried out along the rivers of a wide savanna area of West Africa (approximately 700,000 km(2)) where onchocerciasis was hyperendemic. The level of endemicity began to decrease significantly after 4 years of vector control and became very low in 1989. This situation has been maintained without any vector control activity or chemotherapy, and no incidence of any new cases has been detected. An ophthalmological study carried out in 2000 has confirmed these good results, showing only cicatricial ocular lesions in the examined population. These results led to the conclusion that 14 years of vector control may achieve long-term elimination of onchocerciasis, even in the absence of chemotherapy, provided that the treated areas are not subjected to any contamination by exogenous parasites carried in infected humans or flies.

The indoor use of plastic sheeting pre‐impregnated with insecticide for control of malaria vectors

Objective  To evaluate the efficacy of permethrin‐treated plastic sheeting (ITPS) applied as a lining to the ceiling or walls of rooms against pyrethroid‐susceptible and pyrethroid‐resistant Anopheles gambiae.

Synergy between repellents and non-pyrethroid insecticides strongly extends the efficacy of treated nets against Anopheles gambiae

BackgroundTo manage the kdr pyrethroid-resistance in Anopheline malaria vectors, new compounds or new strategies are urgently needed. Recently, mixing repellents (DEET) and a non-pyrethroid insecticide (propoxur) was shown to be as effective as deltamethrin, a standard pyrethroid, under laboratory conditions, because of a strong synergy between the two compounds. In the present study, the interactions between two repellents (DEET and KBR 3023) and a non-pyrethroid insecticide (pyrimiphos methyl or PM) on netting were investigated. The residual efficacy and the inhibition of blood feeding conferred by these mixtures were assessed against Anopheles gambiae mosquitoes.MethodsDEET and KBR 3023 were mixed with pyrimiphos methyl (PM), a organophosphate (OP) insecticide. The performance of mono- and bi-impregnated nets against adult mosquitoes was assessed using a miniaturized, experimental hut system (laboratory tunnel tests) that allows expression of behavioural responses to insecticide, particularly the mortality and blood feeding effects.ResultsBoth mixtures (PM+DEET and PM+KBR3023) induced 95% mortality for more than two months compared with less than one week for each compound used alone, then reflecting a strong synergy between the repellents and PM. A similar trend was observed with the blood feeding rates, which were significantly lower for the mixtures than for each component alone.ConclusionSynergistic interactions between organophosphates and repellents may be of great interest for vector control as they may contribute to increase the residual life of impregnated materials and improve the control of pyrethroid-resistance mosquitoes. These results prompt the need to evaluate the efficacy of repellent/non-pyrethroid insecticide mixtures against field populations of An. gambiae showing high level of resistance to Ops and pyrethroids.

Characterization of Insensitive Acetylcholinesterase (ace-1R) in Anopheles gambiae (Diptera: Culicidae): Resistance Levels and Dominance

Abstract Characterization of insecticide resistance provides data on the evolutionary processes involved in the adaptation of insects to environmental changes. Studying the dominance status and resistance level represents a great interest, in terms of understanding resistance evolution in the field to eventually adapt vector control. Resistance and dominance levels conferred by the G119S mutation of acetylcholinesterase (ace-1R) of the mosquito Anopheles gambiae s.s. (Diptera: Culicidae) were studied for various insecticides belonging to different classes, using strains sharing the same genetic background. Our survey shows that the homozygote resistant strain AcerKis displayed a very high resistance level to various carbamates (range 3,000- to 5,000-fold) compared with that of various organophosphates (range 12- to 30-fold). Furthermore, the dominance status varied between semirecessivity with fenitrothion and chlorpyrifos methyl insecticides to semidominance with temephos, carbosulfan, and propoxur. These results indicate that this resistance mechanism could spread rapidly in the field and then compromise the use of organophosphate and carbamate compounds in public health. This study underlines the necessity to monitor the ace-1R mutation in natural populations before planning and implementing malaria control programs based on the use of these insecticides.