Tag Archives: malaria

The Other Superbugs: Pesticide Resistant Insects

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!

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

Sterile Mosquitoes: The Next Big Antimalarial?

Catching up on some old news, I noticed that the November issue of the Malaria Journal has a supplement dedicated to the most elegant insecticide ever developed: the sterile insect technique (SIT). As the accompanying press release explains:

SIT involves the generation of ‘sterile’ male mosquitoes, which are incapable of producing offspring despite being sexually active. Because female mosquitoes only mate once during their lifetimes, a single mating with a sterile male can ensure that she will never breed. This leads to an increasing reduction in the population over time, in contrast to insecticides, which kill a certain fraction of the insect population. The supplement features articles reviewing the history of the technique; ethical, legal and social concerns that might arise from it; and detailed reviews of all of the elements required for a successful SIT programme.

The approach was originally developed by Edward Knipling and his colleagues in the 1950s, who used it successfully to eradicate a devastating cattle pest called Cochliomyia hominivorax, or the screwworm fly. It’s been somewhat harder to use against other pests, though, including mosquitoes. To find out why, and to see the state of the science in this nonchemical pest control technique, check out the supplement – it’s open-access.

Malaria Control: Spraying You-Know-What

The US Agency for International Development just awarded a $150 million grant to open a new front in the Bush administration’s anti-malaria effort. The press release, however, has a rather obvious omission. Here’s how it starts:

The U.S. Government, through the U.S. Agency for International Development (USAID), announced the awarding of a $150 million Indoor Residual Spraying (IRS) contract to a consortium headed by Research Triangle Institute (RTI). Indoor Residual Spraying (IRS) is the application of safe insecticides to the indoor walls and ceilings of a home or structure in order to interrupt the spread of malaria by killing mosquitoes that carry the malaria parasite. Malaria is the number one killer in Africa.

And exactly what “safe insecticides” are they referring to? DDT, of course. As I pointed out in an earlier post, DDT can indeed be quite safe in this application, but its revival poses some thorny problems that the Administration might not be prepared to handle. In any case, it’s unfortunate that they felt the need to censor the press release like this. Is this the start of a pattern of obfuscation in this new effort?

DDT: Important Messages, Bad Messengers

Forty-four years after Silent Spring, dichloro-diphenyl- trichloroethane (DDT) is front page news again, and as always happens with this compound, critical, finely nuanced issues are being bulldozed into black and white.

War on Insects

The main story, in case you missed it somehow, is that the World Health Organization (WHO) announced that it would start using DDT to control malaria in Africa. This follows a regime change in the WHO’s malaria program, which is now being run by an outspoken public health campaigner named Arata Kochi, who previously ran the WHO’s TB program.

Indoor spraying of DDT, Kochi argues, is an important weapon against malaria, and this circumscribed use of the notorious pesticide has not been proven to cause environmental harm. The Bush administration and prominent Republicans also support the change, representing an unusual convergence of UN and Administration opinions.

The back story is considerably more complicated.

Kochi seems to be a specimen of a familiar type in public health: the “damn the subtleties, full speed ahead” character. There is a place for that approach, but it can easily backfire. Indeed, Kochi was forced off the TB project because he had alienated too many important supporters, and since he took over the malaria project, half of the senior staff has left.

Meanwhile, Bush administration officials and allies seem to be interested in indoor DDT use primarily as a rhetorical tool to put environmentalists on the defensive this election season. In the press release announcing the change, Senator Tom Coburn (R-OK) even takes the opportunity to tar earlier objections to DDT as “junk science and myths,” leaving no doubt about his motivations or his ignorance of recent research.

We’ve been down this road before, and it ended badly last time.

Let’s begin at the beginning. DDT owes its notoriety to American applied research during World War II. At the start of the war, chemists had known how to synthesize the compound for decades, and a few knew of its insecticidal properties, but nobody had tested it rigorously or turned it into a practical product. It seems unlikely that anybody would have, if it hadn’t fallen into the hands of an obscure group of entomologists at the US Department of Agriculture in 1942.

The USDA scientists had recently been drafted into a critical public health project: preventing louse-borne typhus in troops. They worked methodically, testing every chemical they could find to see what would kill lice. Among thousands of other samples, they received a waxy, granular substance from the Geigy corporation in Switzerland. The manufacturer called it Gesarol.

Gesarol did kill lice, and every other insect in the lab, but a crumbly wax doesn’t work well as a delousing treatment, so the USDA crew did the unglamorous but essential job of reformulating it. By 1943, they were producing large quantities of several formulations, including powders and sprays, and they were referring to Gesarol by its generic name, abbreviated DDT.

The USDA scientists promoted DDT only for a few circumscribed uses, including delousing and malaria control. Does this sound familiar? Indeed, the entomologist leading the effort specifically cautioned against spraying the stuff willy-nilly outdoors, arguing as early as 1944 that DDT was “definitely poisonous,” and that its environmental consequences might be bad. I happen to have an archive of his papers sitting in my closet, as he was my grandfather.

Nurse spraying DDT on a hospital bed

That message became unfashionable after the war, when the USDA reverted to its traditional mission of boosting American agricultural yields. Walter E. Dove left the agency, and the USDA started promoting widespread spraying of DDT on crops.

Just as agricultural use was ramping up, the newly constituted WHO also adopted this miracle compound, putting it to use in an ambitious, military-style campaign to eradicate malaria. Not only was it used inside houses, it was also sprayed from aircraft, trucks, and by hand into every conceivable mosquito habitat. If a little was good, more had to be better, and human health trumped all environmental concerns; damn the subtleties, full speed ahead.

The massive doses of DDT soon bred environmental disaster and widespread insect resistance to the pesticide. The more DDT the WHO and the farmers sprayed, the less effect it had, until the leaders of the malaria eradication campaign were forced to surrender, and the farmers were forced onto a treadmill of chemical dependence.

Given this history, it’s easy to understand why malariologists have resisted using DDT again in malaria-endemic areas. But we’re smarter now, so what could go wrong?

For starters, the new campaign will force rich countries to relax bans on DDT-tainted crops. Otherwise, poor African farmers won’t dare let DDT onto their property, for fear that the tiniest bit of cross-contamination could cost them their best foreign customers. Once regulators comply with this change, what’s to keep farmers from using a little cheap DDT here and there to control field infestations? It does work, and poor countries today face the same pressures to boost agricultural yields that the US faced in 1945.

Meanwhile, an overzealous public health worker might decide to use up some extra spray on a few puddles and ponds where mosquitoes are breeding. Higher government officials might also like that idea. Nuance-averse politicians are already paving the way by arguing that the pesticide’s environmental and health risks are overblown, when in fact they continue to reverberate. It might not be long before we’re parachuting cats onto Borneo.

DDT could indeed be an important weapon in combating malaria, but that will require a carefully constructed, fine-grained plan, not another military-style assault backed by science-blind leaders. Used properly, as originally intended and for a narrowly restricted purpose, DDT could be safe for the world. Unfortunately, the world we live in might not be safe for DDT.