Brown Besier, Department of Agriculture and Food WA, Albany
March 2013

Resistance to the macrocyclic lactone (ML) group of anthelmintics is a serious problem for the Australian sheep industries. When the MLs were first introduced in the late 1980s, resistance was widespread to the older drenches, and the new drench type was a much-needed lifeline, which rapidly transformed worm control.

Unfortunately, the worms fought back very quickly. Resistance to Haemonchus contortus (barbers pole worm) and Teladorsagia (Ostertagia) circumcincta (small brown stomach worm) were both detected within less than 4 years of the release of ivermectin. The rest is history—ML resistance is now present on the vast majority of sheep farms in Australia (although the more potent MLs remain effective on many). We now know far more about the management of drench resistance, but this is of more help with new anthelmintic groups—we can’t turn the clock back once resistance develops.

Who’s who in ML resistance?

The (relatively) good news is that Haemonchus and Teladorsagia remain the only two worm species commonly affected by ML resistance. The bad news is that they are major causes of worm disease: Haemonchus as a cause of sheep deaths, especially in summer rainfall regions, and Teladosagia as one of the ‘scour worms’, of major importance in winter rainfall areas.

All sheep farmers have to control at least one or the other of these two worm types on a routine basis. Hence, although ML resistance does not affect all major types (as resistance to the white and clear drenches does), once detected it affects the value of that group for worm control generally. There are few opportunities to use the MLs as narrow-spectrum drenches, aimed only at specific worm types.

Where the limited range of species affected may have unwittingly helped us is that the MLs have remained effective against worms other than Haemonchus and Teladorsagia—so where the latter were not present as the dominant part of a particular worm burden, an ML drench would at least reduce the effects of the worm species present.

However, this may be changing: is resistance increasing to Trichostrongylus species?

ML resistance in Trichs?

Trichostrongylus (black scour worm) is arguably the most important worm type (genus) in Australia. It occurs in every region, whereas Haemonchus and Teladorsagia are of major importance in more restricted environmental ranges. It has several species (in sheep, four main ones), which allows it to be present across a wide range of climates.

ML resistance in Trichostrongylus has been reported occasionally, initially in goats (famed breeders of drench resistance), then later in sheep, but not as a mainstream problem. However, the common laboratory test to differentiate the larvae of different worm types (eggs can’t be separated on appearance) is not specific: because of overlapping dimensions of the larvae, some Teladorsagia will inevitably be incorrectly identified as Trichostrongylus. The definitive test is based on counting worms in the animal’s gut, but in trials over the past two decades, this test has rarely confirmed Trichostrongylus to be present after use of an ML, whereas Teladorsagia or Haemonchus are commonly present.

Differences between species in the response to drugs varies considerably: some require a far larger amount to kill them than others, and some are not affected at all by a particular drench. One explanation is that the genetic inheritance mechanism differs between species. For Haemonchus and Teladorsagia, it appears that ML resistance is a semi-dominant trait (a significant proportion of worm matings yields partially-resistant offspring), whereas it has been suggested that it is recessive in Trichostrongylus. This is very tricky to sort out.

Some Questions:

There are indications that ML resistance in Trichostrongylus may be increasing. Several laboratories have reported an increase in the number of drench resistance tests in which Trichostrongylus remains present after treatment with an ML, with decreased percentage reductions in these groups. Despite the lack of precision in identifying the worms in resistance tests, the suggestion of an increased prevalence of Trichostrongylus in ML test groups needs investigation.

This raises several queries:

• Why would there be an increase in ML resistance in Trichostrongylus from the apparent very low level over 25 years? If anything, the selection pressure on drenches in general would have decreased as farmers adopt resistance management strategies.
• Why would a change in ML resistance in Trichostrongylus appear to be occurring only in some areas? For instance, there is no such indication in Western Australia, where selection pressures for drench resistance are especially high.
• Why have we not confirmed it by more precise test methods? This is easier: until recently, the only definitive test was to kill sheep and count worms after an ML drench. This is costly and time-consuming, and requires laboratory expertise. As there was no reason to suspect a change to the situation, no specific studies have been done.

Genes to the rescue?

There are now much more powerful laboratory methods than larval differentiations to sort out the identity of worm eggs or larvae. Genomic tests that use DNA differences for species identification have been available for many years, but only recently have they been developed for use in sheep worms. A new and exciting world is looming, whereby we routinely use PCR methods to differentiate worm species both for resistance testing and for routine worm burden monitoring. Genomic tests are also far more accurate than larval differentiations, as apart from negating the measurement overlap problem, they identify to species level, not just to the less-definitive genus.

These tests are only now being developed for use on a routine commercial scale, but they are being increasingly used for research purposes. It will be a simple matter for an investigating laboratory to submit samples from drench resistance tests for PCR analysis, to confirm whether Trichostrongylus is present after ML use, and hence whether the MLs are indeed increasing their coverage of the worm spectrum. If this is confirmed, the total impact of drench resistance on sheep parasite control, and the need to combat it, will be even greater.