Parasitologists from the U.S., Grenada, and Australia recently reviewed other potential biological effects of long-term anthelmintic treatment in horses besides parasite resistance.
Despite the introduction of new and effective anthelmintic drugs since the 1960s, parasitic infections “remain highly prevalent in companion animals worldwide and in humans,” the authors said. They noted that routine and frequent administration of parasite control drugs has elicited resistance, which is heritable between generations of parasites. While fecal egg count reduction testing can measure parasite progeny by adults, it does not provide an accurate count of the animal’s true parasite burden.
Egg Reappearance Period
The egg reappearance period (ERP) describes how long it takes for strongylid egg shedding to reappear following anthelmintic treatment, which has been the basis for optimal treating intervals since the 1990s. However, over the past few decades, the ERP for equine cyathostomin infections has diminished significantly following treatment with ivermectin or moxidectin (macrocyclic lactones). Previous assumptions suggest this points to greater prevalence of anthelmintic resistance (AR). However, the authors argued that a declining ERP might not actually reflect AR but could instead result from the selection of other traits.
The researchers described studies looking at weekly fecal egg counts for the five weeks following moxidectin administration to treat both adult and larval cyathostomins. At two weeks post-treatment, fecal egg counts were negative with efficacy of 99% and recovery of just a few luminal worms. However, fecal egg counts turned positive three weeks later. Because the drugs eradicated nearly all parasite eggs from the horses in the immediate period post-treatment, the results are not indicative of anthelmintic resistance.
Decline in Anthelmintic Performance
The study results show that at five weeks post-treatment, around the time eggs were reappearing, luminal worm counts increased by more than tenfold compared to the two-week analysis. ERPs have decreased from eight to 10 weeks (ivermectin) and 12-16 weeks (moxidectin) to just four to five weeks for either drug. The authors suggested this is the result of a decline in anthelmintic performance rather than anthelmintic resistance, as it does not fit the classical definition of AR.
Evaluation of the large variety of cyathostomin species did not demonstrate that long-term treatment selected for a subset of species with shorter life cycles. Instead, treatments seem to have selected for common species with “phenotypes that can complete their life cycle more quickly. Parasites that develop more quickly and produce offspring prior to subsequent treatment have a large survival and transmission advantage.” Researchers have also reported shortened ERPs for the filarioid species of Onchocerca volvulus in humans when treated with ivermectin.
The authors noted that in horses, anthelmintics retain good efficacy against adult cyathostomins but no activity against encysted larvae, whereas in humans anthelmintics only have efficacy against O. volvulus larval stages and none against adults. Despite these differences, both cyathostomins and O. volvulus have developed a similar phenotype that shortens parasite repopulation rates, independent of anthelmintic resistance.
Additional Factors That Affect Nematode Transmission
Many other factors, including pasture management, pasture quality, and husbandry, affect nematode transmission, the authors explained. Climate also plays an important role. They suggested that adaptation of parasite populations to climate change and altered seasonal patterns could select for specific biological traits that impact anthelmintic performance. Such traits might also be genetically linked to loci that confer AR.
In summary, the authors contended that AR is one biological change associated with evolutionary pressures overlaid on the use of anthelmintic drugs. However, researchers should consider and analyze other biological changes that lead to a decrease in anthelmintic performance.
Nielsen, MK.; Kaplan, RM.; Abbas, G.; Jabbar, A. Biological implications of long-term anthelmintic treatment: what else besides resistance are we selecting for? Trends in Parasitology November 2023, Vol. 39, No. 11; https://doi.org/10.1016/j.pt.2023.08.002