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Reversion: Do worms become susceptible again to drenches not used for years?

What happens to the effectiveness of a drench group when it hasn’t been used for many years?

Typically, this question arises way down the track after a drench group has been taken out of service following a treatment failure. In summer rainfall regions, closantel (an active from the salicylanilides/phenols group; SA), a narrow spectrum drench used to control barber’s pole worm, may not have been used for 10 years or more. In other regions it might have been benzimidazole (BZ; white) drenches.

This poses two key questions. Will the effectiveness increase, and if so, for how long will the benefit last?

Why would the effectiveness improve in the absence of use?

Drench resistance is a genetic trait, meaning that it is inherited, with changes accumulating in the worm population over time in response to drench use. This leads to a progressive increase in drench resistance, which sheep producers see as a decline in drench efficacy. Drench resistance is said to occur when a treatment fails to reduce worm egg counts by at least 95%, by which stage the number of resistant genes is well entrenched in the worm population.

Reversion

Reversion is not well understood. It is speculated that the main way in which the effectiveness of a drench might improve after its removal from use is if resistant worms were less fit. Fitness refers to the ability of worms to reproduce, survive and complete their life cycle. Any negative changes reduce fitness and result in fewer resistant worms contributing to the population.

Less fit worms might have lower egg production, be less successful in developing from egg to infective larvae, have shorter survival as infective larvae, have lower rates of establishment in the host, or a shorter life span as adult worms. Negative changes in these life traits make the worms less fit and result in a smaller proportion of those resistant worms as part of the overall worm population over time. This process is referred to as reversion.

If drench-resistant worms were less fit, then it is likely that removal of that drench from use would result in those worms representing a smaller and smaller proportion of the population over time.  This would be observed as an improvement in the effectiveness of that drench group when it is again used, because the susceptible worms are better able to survive in the absence of the drench. Under this hypothetical situation, the drench would have been the only factor that allowed the less fit, but drench resistant worms, to flourish and dominate the population.

There may be other mechanisms such as "counter-selection", where resistance to one drench group may increase susceptibility to another unrelated drench group and result in reversion, but this possibility has little supporting evidence and remains poorly understood.

Evidence for and against reversion

A number of laboratory studies conducted with BZ-resistant barber’s pole worm in the late 1970s and early 1990s demonstrated that rather than being less fit, these resistant worms had better fitness and caused more damage to the sheep. In contrast, laboratory studies with BZ-resistant brown stomach worms showed no difference in fitness, but BZ-resistant black scour worms had poorer fitness and were less pathogenic when artificially introduced to gerbils (desert rat).  

The relationship between fitness and BZ resistance remains uncertain, or is dependent on worm type. Unfortunately, there is no evidence to support or refute reversion to drench susceptibility for other drench groups. More recently, a New Zealand study suggested that the use of multi-active combination drenches may improve reversion to drench susceptibility, especially when high levels of refugia are maintained and this suggestion awaits confirmation.

Reversion in the field

It is not uncommon for producers to report good results from the initial use of a drench group that had not been used (because of low effectiveness) for a long period. Aside from the possibility of reversion, it’s possible that the improved effectiveness is due to a change in the genetic make-up of the worm population with a greater proportion of heterozygotes or carriers of the resistant genes (worms with a mixture of drench resistant and susceptible genes) due to mating between resistant and susceptible worms (the susceptible worms may have existed in refugia, that is on the paddock as larvae when a drench had been given). Such a change requires heterozygote worms to be more susceptible to the drench.

Unfortunately, it is also common for producers to report that effectiveness of the “re-established” drench group quickly declines from the encouraging results obtained from the initial re-use. Introducing the drench group would remove many of the heterozygotes and, of course, the susceptible worms from the population resulting in a fairly fast re-establishment of drench resistant population over one or a few uses of the drench.

Take home message

Drench groups that have been out of service for a long period of time might provide a valuable, but very temporary, addition to a drench program. Whether the temporary improvement in effectiveness is due to reversion, caused by a lack of fitness, or simply due to a change in the genetic make-up of the worm population, is still uncertain.

So in response to the questions posed at the beginning of this article:

Q) What happens to the effectiveness of a drench group when it hasn’t been used for many years?

A) It very likely will increase.

Q) If the effectiveness increases, how long will the benefit last?

A) It is likely that it will be short-lived but attention to using effective multi-active combination products will extract the most from the re-established drench group.

WormBoss has more information about managing drench resistance.