In 1955, the World Health Organization launched an ambitious campaign to eradicate malaria. The effort relied on new, synthetic antimalarial drugs such as chloroquine and a miraculous new insecticide called DDT. Initially, it went pretty well: several countries’ malaria rates plummeted. Then it fell apart. The malaria parasites became resistant to the new drugs, and the mosquitoes which transmit the disease became resistant to DDT. After two decades of work and a massive expenditure of money and effort, the WHO gave up. Once again, Plasmodium and Anopheles had kicked Homo‘s butt.
Quick Henry, The Flit!
By the 1990s, a new generation of public health officials was ready to take another run at the problem. Armed with a wider spectrum of antimalarial compounds, campaigns such as Roll Back Malaria seemed well prepared to deal with the problem of drug resistance by the parasite. Insecticide resistance was a different story. As before, the WHO-sponsored effort would rely heavily on a single chemical class to combat mosquitoes. This time, the effort favored pyrethroids.
The WHO’s enthusiasm for pyrethroids was understandable. As insecticides go, they’re pretty spectacular. These compounds are either mixtures or derivatives of a natural plant product called pyrethrum. Pyrethrum is only modestly effective by itself, but in the late 1940s chemists discovered that mixing it with another compound, piperonyl butoxide, boosts its killing power dramatically. Since then, researchers have synthesized several variants of pyrethrum, such as permethrin and deltamethrin, that are even more effective. What really makes these pesticides blockbusters, though, is that they’re highly specific for arthropods; their human and environmental toxicities are extremely low.
Because they’re so effective and nontoxic, pyrethroids are now the dominant over-the-counter insecticides worldwide. If you walk into the hardware store to buy some bug spray, you’ll see what appears to be a huge variety of products, but a close reading of the ingredient lists reveals that they’re almost all the same. Raid Ant Killer, Ortho Garden Insecticide, generic wasp killer, and most of the other colorful containers are just different package designs. What you’re really looking at is shelf upon shelf of pyrethroids.
We should know better. Bacteria, viruses, fungi, and protozoans have repeatedly taught us the same fundamental lesson about adaptation: if you keep throwing one chemical at a class of organisms long enough, they’ll eventually get used to it. Inevitably, the same has now happened with insects and pyrethroids.
In the tropics, particularly Africa, pyrethroid resistance has become a major public health problem. Because malaria control in poor, hot countries relies so heavily on pyrethroid-treated bed nets, resistant mosquitoes can now bypass the only real barrier between them and their victims.
Using these compounds willy-nilly has also spawned other problems. The treated bed nets, plus indoor spraying, have placed heavy selective pressure on all of the other insects that live in close association with people. Bedbugs, for example.
Indeed, bedbug populations have become highly resistant to pyrethroids, which is why homeowners’ DIY efforts to control them seldom work out. There’s been some debate about where that resistance came from, but recent results on US bedbug populations suggest that this resurgent pest is an import. It’s possible – even likely – that widespread pyrethroid use to combat mosquito-borne diseases in developing countries has spawned these new populations of superbugs.
Switching to other pesticides may help, at least sometimes with some insects. A study in Benin found that bendiocarb-treated bed nets were very effective against pyrethroid-resistant mosquitoes. Unfortunately, bendiocarb is highly toxic to birds and fish, and acutely toxic to humans in high doses. Treating a bed net with it is probably okay, but it’s not the kind of thing that should be sprayed around the house by amateur exterminators.
Nor is chemical-switching a panacea. Turning back to bedbugs, it appears their pyrethroid-resistance mechanisms are many and varied. Deep sequencing analysis revealed that the pesticide-resistant strains in a US infestation carry multiple changes in multiple genes, including increased expression of general detoxifying enzymes that could be useful against a broad spectrum of chemicals.
The solution, if there is one, will have to be twofold. First, we need a sustained research effort to understand the basic mechanisms of insecticide resistance and find new compounds that can overcome it. Second, both pesticide makers and public health officials need to take more responsibility for how these products are actually being used in the field, with a special focus on the problem of resistance. Our approach to distributing these powerful and important chemicals needs a thorough debugging.
Akogbeto, M., Padonou, G., Bankole, H., Gazard, D., & Gbedjissi, G. (2011). Dramatic Decrease in Malaria Transmission after Large-Scale Indoor Residual Spraying with Bendiocarb in Benin, an Area of High Resistance of Anopheles gambiae to Pyrethroids American Journal of Tropical Medicine and Hygiene, 85 (4), 586-593 DOI: 10.4269/ajtmh.2011.10-0668
Adelman, Z., Kilcullen, K., Koganemaru, R., Anderson, M., Anderson, T., & Miller, D. (2011). Deep Sequencing of Pyrethroid-Resistant Bed Bugs Reveals Multiple Mechanisms of Resistance within a Single Population PLoS ONE, 6 (10) DOI: 10.1371/journal.pone.0026228
