PermaNet® 3.0 - Insecticide Resistance

The Insecticide Resistance Action Committee (IRAC) defines insecticide resistance as “the selection of a heritable characteristic in an insect population that results in the repeated failure of an insecticide product to provide the intended level of control when used as recommended.”

Types of Insecticide Resistance

Resistance in mosquitoes can be due to one or a combination of the following mechanisms:

• Metabolic resistance (e.g. P450's/ esterases)
• Altered target-site resistance (e.g. kdr)
• Behavioral resistance
• Reduced penetration

Resistance Development

• Natural selection allows pre-adapted insects with resistance genes to survive and pass on the resistance trait to offspring.
• As more product is applied, the resistant population keeps increasing while the susceptible individuals are eliminated by the insecticide.
• The product is eventually no longer effective.
• Speed of resistance development depends on many factors such as reproduction time, frequency of application of pesticides, and the proportion of susceptible insects.

The Complexities of Resistance

In malaria treatment

• Malaria case management forms one of the core interventions of the global strategy for malaria control. Prompt and accurate diagnosis are needed for effective treatment.
• Chloroquine was introduced as the antimalarial medicine of choice in 1945.
• In the mid-seventies, resistance of malaria parasites (Plasmodium spp.) to chloroquine became a problem in  Africa¹.
• The unprecedented scale of the rapidly-rising resistance of Plasmodium falciparum to conventional monotherapies such as chloroquine, sulfadoxine-pyrimethamine (SP) and amodiaquine is currently  threatening global malaria control efforts².
• Multi-drug resistant falciparum malaria is now widespread in South-East Asia and South America. Africa, the continent with the highest burden of malaria, is also being seriously affected by drug resistance².
• In 2004, the WHO revised malarial treatment policies, and recommended all countries opt for a combination treatment, preferably an artemisinin-based combination therapy (ACT)².

In malaria prevention

• Pyrethroids are currently the only insecticide class recommended by the WHO for use on bednets, for reasons of safety, efficacy, acceptability and cost.
• No new class of insecticides has been introduced for use in public health for over 20 years.The extensive use and misuse of insecticides for agriculture has contributed to the development of resistance in public health pests^3,4. Resistance in mosquitoes has also been linked to IRS5,⁶, ITNs^7,8 and use of household insecticide (sprays, coils etc)⁹.
• Extensive resistance development has resulted in reduced efficacy of pyrethroid-treated bednets¹⁰, which may have a negative impact on malaria prevention and control.

References

1. Carter, R. & Mendis, K. N. (2002) Evolutionary and historical aspects of the burden of malaria. Clin Microbiol Rev 15: 564-594.
2. http://www.who.int/malaria/docs/who_apt_position.htm
3. Djouaka, R. F. et al (2008) Expression of the cytochrome P450s, CYP6P3 and CYP6M2 are significantly elevated in multiple pyrethroid resistant populations of Anopheles gambiae s.s. from Southern Benin and Nigeria. BMC Genomics 9: 538.
4. Chouaibou, M., J. et al (2008) Dynamics of insecticide resistance in the malaria vector Anopheles gambiae s.l. from an area of extensive cotton cultivation in Northern Cameroon. Trop Med Int Health 13: 1-11.
5. Brogdon, W.G. et al (1988) Microplate assay analysis of reduced fenitrothion susceptibility in Haitian Anopheles albimanus. J Am Mosq Control Assoc 4:152-158.
6. Lines, J.D. (1988) Do agricultural insecticides select for insecticide resistance in mosquitoes? A look at the evidence. Parasitology Today 4:S17-S20.
7. Corbel, V. et al (2004) Dosage-dependent effects of permethrin-treated nets on the behaviour of Anopheles gambiae and the selection of pyrethroid resistance. Malar J 3: 22.
8. Stump, A. D. et al (2004) Dynamics of the pyrethroid knockdown resistance allele in western Kenyan populations of Anopheles gambiae in response to insecticide-treated bed net trials. Am J Trop Med Hyg 70(6): 591-596.
9. Akogbeto, M. & Yakoubou, S. (1999) Resistance of malaria vectors to pyrethrins used for impregnating mosquito nets in Benin, West Africa. Bull Soc Pathol Exot 92(2): 123-130.
10. N’Guessan, R et al (2007) Reduced efficacy of insecticide-treated nets and indoor residual spraying for malaria control in pyrethroid resistance area, Benin. Emerg Infect Dis 13(2): 199-206.