Malaria: synergy of insecticide mixture applied to mosquito nets against resistant Anopheles

Malaria is a major scourge on health in many parts of the world, particularly in Sub-Saharan Africa where over 90% of declared cases have been recorded. Mosquito nets impregnated with insecticides are considered as a good prevention and control weapon against the mosquito vectors, in particular in areas where malaria is strongly endemic.

The only insecticides currently recommended by WHO (1) are pyrethroids whose rapid action causes a “knock-down (KD)” (2) effect and high mortality when mosquitoes come into contact with it, at much smaller doses than those which are toxic for humans and other mammals. Resistance is, however, emerging among many vector species, including Anopheles gambiae in tropical Africa. IRD scientists from the research unit “Vector population characterization and control” therefore investigated a new strategy. This involves combining as a mixture, in the same mosquito net, two insecticides with distinct action mechanisms, a pyrethroid (bifenthrin) and a carbamate (carbosulfan) (3). The results of a recent trial conducted in the Bouaké region of the Ivory Coast show that use of doubly impregnated mosquito nets are effective in terms of mortality and blood-feeding inhibition among adult A. gambiae and Culex resistant to one or other of the insecticides. The positive interaction, or synergy, which sets in between the pyrethroid and the carbamate gives such combined impregnation a clear advantage. The process requires doses far below those usually applied in single impregnation. It consequently reduces the cost and toxicity of the treatment, thus ensuring the safety of users, especially of children.

The synergy between the pyrethroid and the carbamate underwent prior investigation in laboratory experiments on adult A. gambiae susceptible to these two classes of insecticide. The strongest synergy of action was observed in the proportion of 6.25 mg/m2 of carbamate (in other words 1/50th of the recommended dose) to 25 mg/m2 of pyrethroid (1/2 the recommended dose). That ratio was subsequently repeated in the Ivory Coast field trial. This mixture led to a mosquito mortality rate of 80%, about twice the expected rate assuming absence of any interaction between the two insecticides (41%). However, if the carbamate proportion was stepped up, there was a corresponding loss in the speed of action and the KD effect of the pyrethroid. This antagonism, strongest when the minimum effective dose of pyrethroid was combined with the maximum recommended dose of carbamate, was attributable to carbamate’s irritant and repellent action which keeps the mosquitoes away and precludes sufficiently long tarsal contact with the pyrethroid for it to work.

This control strategy, based on the use of double-impregnated mosquito nets and the positive interaction between two insecticides of different classes, could be implemented as an effective barrier against A. gambiae, the major malaria vector in Sub-Saharan Africa. The results obtained in the Ivory Coast against resistant mosquitoes also offer the prospect of extending the approach to other harmful insects, such as Culex quinquefasciatus, the main nuisance insect in urban areas. Research work continues, calling on such techniques as electrophysiological methods to unravel the physiological mechanisms brought into play on activation of the pyrethroid-carbamate synergy effect. A better understanding of these interactions should provide a basis for more efficient control strategies, more selective towards nuisance insects and vectors of human diseases.