Insecticide Resistance — The challenge of Evolution
Time is against us in achieving our goals. It is more than 30 years since the pyrethroids were introduced as a radical new anti-malaria insecticide. And these were the last new mainstream class of public health pesticides to be developed. Pyrethroids are the insecticides used for more than 60 per cent of the IRS and 100 per cent of the LLIN market. Resistance to pyrethroids in the major vectors of malaria poses the greatest current threat to malaria control.
Resistance is a problem because:
- we are totally reliant on pyrethroids for LLINs (although we're working on some nets treated with two insecticides which will provide a temporary stop-gap until the new generation of anti-malaria insecticides are available)
- resistance can occur at a low frequency for many years until a ‘tipping-point’ is reached, when resistance rises extremely rapidly, which can result in catastrophic failure of an intervention. We are almost at that point in many countries in sub-Saharan Africa.
The more intense the control efforts as elimination efforts are established, the greater the selection pressure for resistance, and the more rapidly the ‘tipping-point’ is reached. That's why a single insecticide approach is doomed to failure, and why we're planning for at least three different classes of insecticide with novel modes of action.
Resistance can be managed
Resistance management is feasible, and the long term sustainability of this has been demonstrated in public health with the Africa Onchocerciasis Control Programme and in agriculture with the cotton crop pest control systems. To be sustainable resistance management ideally requires three active ingredients with different modes of action and with initial susceptibility to all three in the insect vector. The insecticides can then be deployed in rotations or fine scale mosaics, as demonstrated by large scale trials in Mexico, or as mixtures as advocated for malaria drug resistance management for ACTs. Resistance management should be adopted as soon as the appropriate new AIs are available to do this.
Control programmes need to be able to monitor their mosquito populations and respond as soon as a ‘tipping-point’ of operationally significant resistance is apparent. However, resistance is poorly documented in most malaria endemic countries, so we do not know the extent of its geographical spread and we have no means of rapidly differentiating between operationally significant and non-significant resistance. To date we have been able to empirically detect and respond to operationally significant metabolically-based pyrethroid resistance in southern Africa, but there has been a massive rise in a similar form of pyrethroid resistance in West Africa over the last 2-3 years, the impact of which on either LLINs or IRS is poorly documented.
By developing simple tools to help define and monitor resistance in an operational setting the IVCC has already started to provide a partial solution to the resistance issue. The major gaps, of a credible replacement for pyrethroids on nets and, once this is available, a strategy for rapidly replacing the hundreds of millions of nets in circulation when we reach the resistance tipping point, remain.