Dealing with superworms

The term ‘superbug’ has become popularized in recent times, and generally carries with it a panicky/doomsday connotation. It refers to a pathogen that has become resistant to most or all of the drugs we have to treat it, and that is rightly scary. When you hear superbug, it is often in reference to MRSA (methicillin-resistant Staphylococcus aureus), a nasty sort of bacteria that can be deadly to individuals with weakened immune systems (like sick people in a hospital). We really only have 1 drug left that works against MRSA, and sometimes even that is failing. These superbugs get a lot of attention for very good reason, so why don’t we ever hear about the superworms?

By this I mean parasitic worms that have acquired resistance to most or all of the drugs that we have available, and these days they are truly rampant. There are 3 kinds of drugs that are used to treat worms: BZ (benzimidazole), LV (levamisole), and IV (ivermectin). These drugs have been in use around the world for many decades, and until last year (when monepantel and derquantel were licensed for use in Europe and Australia) they were essentially the only drugs available. Superworms are especially troubling when we’re talking about livestock, particularly sheep and goat farms. Here are some numbers from a recent review from (Kaplan 2012) on the percentage of farms that report some level of resistance:

Percentage of farms reporting drug resistance
BZ LV IV Combo
USA 97.8 54.3 76.1 47.8
Brazil 100.0 100.0 100.0 95.2
Australia 100.0 100.0 80.0 60.0

Those numbers don’t mean that the farms have been completely overrun with drug-resistant worms (though some have), but they do show that drug-resistant worms can be found almost everywhere. And if those worms are present in your livestock, odds are that they will eventually take over. In fact current methods of dealing with worms, like scheduled drug treatment of the entire herd, almost guarantee it.

Worms are quite different from bacteria like MRSA, and one of the traits that lends itself to drug resistance is that they release eggs (tens of thousands per animal per day!) that can survive on the pasture for months or years. If an animal is sick, you can treat it with a drug, but there is no way to treat all of the eggs on the pasture. That means that though all of the worms in that animal may be killed by the drug, in 2-5 weeks the animal will be reinfected by the eggs that remain where it lives and eats. 

The population of worms on a farm is truly massive. That means that eventually, just due to random chance, some of those worms will happen to be resistant to your drug. The problem comes when you treat all of your animals with that drug, as it will kill all of the worms except for the resistant ones. That means that for 2-5 weeks, all of the eggs being released from your animals are from worms that are resistant to the drug. Over time, repeated treatments cause more and more of the eggs on the pasture to be from resistant worms, so every time your animals are treated, more and more of the worms that reinfect them will be drug resistant. Here’s a graphic illustrating the process (the black box indicates the pasture, the orange worms are kill by drug and the red worms are resistant):

resist_fig

As you can see, the events above cause more and more of the worm population to be drug resistant over time, and in D the top sheep has become heavily infected and needs a treatment that may not be effective. Unfortunately, this is what is happening all over the world, as current worm management practices in many countries are to dose the entire herd on a scheduled basis regardless of how infected each animal might be. The rapid rise of resistance has led to calls for new worm management practices to be adopted by farmers, one of which is called refugia management (Besier 2012) and (Kenyon 2012).

This strategy is centered around the idea that worms have been around almost as long as there have been animals to infect, and so most of the time an animal can carry a reasonable number of parasites without actually being harmed. So you don’t give drugs to the animals that appear to be healthy, and only treat those that are showing the negative symptoms of a parasite infection. Besides saving farmers money on the drugs themselves, this strategy dramatically slows down the rise of resistance. Here’s a graphic with the same scenario as above, save that only the heavily infected sheep is given the drug:

resist_fig2

As you can see, while the proportion of resistant worms did go up, it was far more slowly than in the first scenario, as the resistant eggs released in panel C are diluted down by a much larger number of new susceptible eggs. In this scenario, if one of the animals is in need of drugs, the prevalence of resistance should be low enough that they are effective. These ideas are relatively new, but there are already some studies (Woodgate 2010) that seem to indicate this is a feasible strategy to manage parasites while prolonging the effectiveness of the few remaining drugs we have.

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