ScienceDaily (Nov. 5, 2012) — Mosquitoes that carry malaria are constantly adapting. Some develop resistance. Others alter their behaviour. Mosquitoes of the genus Anopheles, the vectors of malaria, always find a way to foil human attempts to protect themselves from this disease.

Researchers from the IRD and their partners(1) have revealed their great capacity for adaptation, which weakens the strategies to combatting their presence, recommended by the WHO. A clinical trial conducted in some thirty or so villages in Benin demonstrated that, the combined use over an 18 month period of mosquito nets impregnated with deltamethrin, and another powerful insecticide in spray form inside the homes, did not lead to a decline in the disease. Neither the number of cases nor the prevalence of the infection(2) among young children were reduced in comparison with the use of mosquito nets alone. In some localities, the introduction of nets led to a change in the feeding habits of the insects of the Anopheles genus, which usually bite at night time. They are now rife outside dwellings at dawn.

The long-term effectiveness of the current measures to prevent and combat the disease is therefore called into question. Scientists will once again need to innovate if we are to one day eliminate this disease for good.

On the recommendations of the WHO, 290 million impregnated mosquito nets were delivered in sub-Saharan Africa between 2008 and 2010, thus providing the means to protect 580 million people from malaria. At the same time 80 million people, or 10% of the endangered population, also had the walls of their homes sprayed with insecticides. Nevertheless, with 200 million people still affected every year and over 700,000 deaths all over the world, of which 80% in Africa, the disease continues to be a major threat to public health. The main obstacle to reducing the disease is the enormous ability of the mosquitoes that carry it to adapt to pyrethrinoids, the officially recommended insecticides. As revealed by recent studies undertaken by researchers from the IRD and its partners(1) in Benin, the resistance of the main vector species, Anopheles gambiae, to these products is significantly increasing and weakening the strategies of the country's National Programme to Combat Malaria. The other major vector in Benin, Anopheles funestus, has for its part opted for another tactic: avoiding all contact with insecticides by modifying its feeding habits.

A combination of measures

A species with a particularly strong capacity for resistance, A. gambiae has succeeded in mutating genetically to withstand the increasing exposure to pyrethrinoids. To counter this phenomenon, the WHO has for several years been recommending the combined use of mosquito nets impregnated for long-term effectiveness, with carbamate sprays, another group of insecticides, inside the home. The latter act in a different way against the insects' nervous system, and are extremely powerful. Spraying these insecticides on the walls of dwellings constitutes a promising way of slowing down the appearance or development of resistance, due to the effect of the simultaneous exposure to different products.

The mosquito continues to mutate

In order to verify the effectiveness of this new "2 in 1" approach, the research team conducted a clinical trial in almost 30 villages in Benin. After placing mosquito nets impregnated with pyrethrinoids and spraying carbamates inside homes, the scientists monitored the transmission and number of cases of malaria in children under six years old -- who represent 85% of victims in total. They observed that after 18 months the combination of protective measures did not lead to a decline in the disease, whether on a clinical, parasitological or enthomological level. Neither the number of cases nor the prevalence of the infection through Plasmodium falciparum (the parasite responsible for the infection) were reduced in young children. Moreover, the number of mosquitoes carrying the mutation known as kdr, to which they owe their capacity for resistance, has considerably increased, passing from 20% to over 75% in 18 months. The combined strategy has thus not made it possible to slow down the emergence of the mutation in Anopheles gambiae. This failure may partly be explained by the short period of effectiveness following the spraying of earth walls in dwellings (the porous substrata absorb the insecticides).

Mosquitos with flexible hours

Surprisingly, Anopheles funestus did not put up resistance to pyrethrinoids in the same way as its tough cousin. Confronted with the introduction of the insecticides, it adapted its behaviour. A second study reveals that A. funestus, which is used to attacking inside the home, is now biting more frequently outside dwellings. Only one year after the massive deployment of impregnated mosquito nets in the villages being studied, researchers observed that the proportion of mosquitoes defined as "exophagous" had risen from 45% to nearly 70%. Furthermore, instead of biting its victims during their sleep in the middle of the night, it now waits until the early hours of the day when people leave their homes to go to work. Consequently, the theory of exclusively nocturnal vectors of malaria now needs to be revised, especially when the mosquitoes are exposed to heavy pressure from insecticides.

The deployment of antivector strategies has led to a major reduction in malaria morbidity and mortality in Africa. However, these two recent studies question their long-term effectiveness. Incidentally, an upsurge in cases has recently been reported in other countries.

These studies underline the need to develop second-generation instruments that will make it possible to prevent the transmission of malaria outside the home. Odour traps, currently still at the prototype stage, or hormone confusion techniques are promising directions envisaged by the researchers concerned.

[Notes]

(1) These studies were conducted in partnership with the Enthomological Research Centre in Cotonou and the French Embassy in Benin, the Institut Pasteur in Madagscar and Aix-Marseille University.

(2) The prevalence of the infection is the percentage of children who are not ill but are carriers of the parasite responsible,Plasmodium falciparum