We have made great progress in recent years in combating malaria. The number of deaths globally has fallen by 60 percent and the number of malaria cases by 37 percent since 2000. It’s within our reach to eradicate malaria altogether. But a threat has arisen that may prevent us reaching this goal — insecticide resistance.
Vector control has been an important weapon in the fight against malaria. Indoor residual sprays and treated bed nets are now in use widely across Africa and Asia to kill mosquitoes and protect people. However, the Anopheles mosquito, the vector that transmits malaria to humans, is becoming increasingly resistant to pyrethroids, one of the most commonly used insecticides.
Resistance is also emerging among the other three insecticide classes used in vector control. A recent study by Hilary Ranson and Natalie Lissenden suggests that, in Africa, the resistant population of malaria-transmitting mosquitoes already outnumbers those that are susceptible. As Janet Hemingway and her colleagues say in a paper published in February this year, “This is a prelude to rising incidence of malaria and fatalities.”
Experts agree that new insecticides with new modes of action are urgently needed and scientists are working on innovative products that could provide a solution. But although several new products have been developed that are intended for use in areas of insecticide resistance, they have yet to be approved or implemented on a wide scale.
With the growing threat of insecticide resistance, there is great potential to lose existing vector control products and create an innovation pile-up. What do we need to keep up with the mosquito?
• A more pragmatic approach to accelerate the evaluation of innovative new tools that have already been extensively tested for effectiveness during the product and dossier development phases.
• Normative guidance in a clear and understandable format to guide countries and donors on where and when new products should be used and prevent delays in the implementation of new technologies.
• Continued investment in product development activities and support for the maintenance of existing vector control products to enable effective vector control to continue.
The current World Health Organization process of evaluating new products and developing normative guidance takes a long time. The system has been designed this way for good reasons, as the main purpose is to prevent disease effectively and safeguard human health.
But from where we are standing today — with the chance either to eradicate malaria altogether, or to succumb to increased resistance and see the number of cases rising again — it is time to work out a more pragmatic approach and speed up the introduction of new products.
As an example, 20 years ago BASF launched a new insecticide for crop protection called chlorfenapyr. It has a different mode of action to pyrethroid-based insecticides and can therefore kill insects that are resistant to pyrethroids. This makes it interesting for public health uses, too.
BASF has repurposed chlorfenapyr for use in public health and developed a treated bed net and an indoor residual spray using this active ingredient. Both products have been tested in the field with good results. Now they are with WHO for official testing and recommendation under the WHO Pesticide Evaluation Scheme.
A stumbling block to progress is that WHO’s standard approval tests are designed for insecticides with a mode of action like that of pyrethroids. Pyrethroids kill insects fast — chlorfenapyr does not. It is still effective, but the insect has to metabolize the insecticide first before it becomes active.
Frustratingly, precisely the difference that makes chlorfenapyr a promising tool for combating resistance is also the reason it appears to fail in WHO’s standard tests. A more appropriate testing methodology is needed. As a recent study by Richard Oxborough and colleagues concluded, testing methods should be tailored to the characteristics and mode of action of each insecticide class.
Scientists from BASF and other companies have devoted years to this research and are now breaking new ground with insecticide products that respond to the resistance problem. If we are to achieve the Sustainable Development Goal of ending malaria epidemics by 2030, we need to develop a more streamlined approach to getting these products approved and providing normative guidance. The countries affected need to know what to do when they detect resistance, and when and how to implement innovative products. These delays are frustrating for us and for the countries but, more importantly, while we wait for the process to run its course, resistance is increasing and people are dying.
Elimination of malaria is possible, but only if we tackle resistance faster.
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