Computer model paints a 40-year picture of future worm resistance in horses

While some individuals chronicle the lifestyles of the rich and famous, equine parasitologist Martin Nielsen and his colleagues have been doing something similar with a far less star-studded line-up — small strongyles.

Nielsen and fellow researchers Christian Sauermann and Dave Leathwick have successfully applied computer modeling to simulate the effect of different factors on the development of small strongyle resistance to the common wormer ivermectin over 40 years.

The findings, reported in the journal Veterinary Parasitology, paint the clearest picture yet of how different deworming strategies are likely to play out in decades to come.

“It has taken us five years to get this model developed,” Nielsen, who is with the Maxwell H. Gluck Equine Research Center at the University of Kentucky, told Horsetalk.

“Drug resistance is slow to develop in worm parasites. It typically takes decades to emerge, so it becomes almost impossible to monitor in real-time.

“With the model we can make predictions for 20, 30, 40 years or more in the matter of a few hours.

“This will help us better understand drug resistance and help us identify the best ways to counteract it going forward.”

Small strongyles, or cyathostomins, infect virtually every grazing horse. They are capable of triggering a severe disease syndrome known as larval cyathostominosis.

Resistance in small strongyles is now very common, with reports of resistance to all three of the currently available deworming drug classes.

Parasitologists have been urging horse owners to move away from strictly calendar-based worming to a targeted program based on surveillance.

Current recommendations centre around using fecal egg counts to identify high egg shedders for dosing.

“But, virtually nothing is known about the effectiveness of these recommendations, nor their applicability to different climatic regions, making it challenging to tailor sustainable recommendations for equine parasite control,” the researchers said in their paper.

In their study, they developed a computer model able to replicate the dynamics of the life stages of small strongyles both on pasture and in the host.

Nielsen described the years of work required to generate the model.

“We started by reading through all available literature about the biology, life-cycle, host immune responses, and mechanisms of drug resistance. That was a huge effort.

“Then, we started drawing the outline of the model. We looked at every stage of the life-cycle and defined how it would develop to the next stage. We took into account factors affecting the speed of development, and estimated the proportion of parasites that would successfully make it to the next stage.

“For the external stages – eggs and larvae on pasture – we designed the model to take into account temperature and precipitation with data obtained from weather stations. We then validated the model against published data to check if the worm numbers were realistic.

Finally, the model incorporated known genetics related to wormer resistance.

The researchers input weather data representing four different climatic zones: a cold humid continental climate (Dickinson, North Dakota), a temperate oceanic climate (Muencheberg, Germany), a cold semi-arid climate (Pecos, Texas), and a humid subtropical climate (St Leo, Florida).

They were able to track the likely path of resistance over 40 computer-generated years, evaluating the effects of climate and seasonality on resistance development.

The study team was also able to evaluate the impact of recommended selective drenching programs on delaying resistance development.

The scientists found that, based on the computer analysis, the month of treatment had a major impact on long-term resistance development in colder climates, but not so in a humid subtropical climate.

Increasing the frequency of treatment was found to increase resistance development in all climates, while moving from six to four treatments a year resulted in only a minor reduction in resistance development.

“However, the results also indicated that reducing the number of annual treatments from six to four, while continuing to treat all horses, is likely to have only a minimal benefit in slowing resistance development.

“Currently, many horse owners are struggling to achieve even this modest level of reduction in the number of treatments administered.

“To achieve significant gains in slowing resistance development, the model indicated that a number of annual treatments as low as two may be necessary if all horses are still to be treated on every occasion,” they reported.

Turning to their climate findings, the researchers said that, at low treatment frequencies, it appeared that the month became an important consideration in certain climates.

The timing of even just one treatment had a large impact on the development of resistance in the three  evaluated seasonal climates. Resistance was generally slower to develop when treatments were given in winter or early spring.

These periods coincided with low rates of development of eggs to infective third-stage larvae on pasture, suggesting that worms surviving treatment at these times make a smaller contribution to subsequent pasture contamination.

In contrast, in a subtropical climate offering year-round favourable conditions for small strongyles, the time of the year had limited, if any, effect on the rate of resistance development.

“This could be because of a less synchronized pattern with adult parasites establishing and being replaced over the course of the entire year.”

Regardless of the mechanism, the modeling indicated that, in some climates, the timing of treatments may be important in reducing the rate of resistance development.

A combination of one or two strategic treatments given to all horses and one or two selective treatments given only to horses with higher eggs counts had vastly different outcomes, depending on whether all horses were treated in April in each of the selected climatic region or only selectively treated.

In the three seasonal climates used in the modeling, resistance development was substantially delayed when selective treatments were given in spring, compared to the scenarios where all horses were treated in April.

Treatments given early in the parasite transmission season will have a big impact on resistance development as surviving worms will live through the entire grazing season and contaminate the environment with resistant genes, they said.

“This suggests that selective therapy should be encouraged for spring treatments, whereas strategic treatments (administered to all horses) appear better suited for autumn treatments, where pasture contamination by the end of the grazing season is declining and adult worm burdens are approaching the end of their life span.”

The model suggests that treating all horses twice a year offered a marked reduction in the rate of resistance development compared to treating horses four or six times a year, but the timing of these two treatments in relation to climate is important.

Nielsen, who continued work on the project during his sabbatical in New Zealand last year, says it will also serve as an excellent tool to highlight knowledge gaps and identify research needs.

The researchers have just published another paper describing the model, and one centering on the genetics has just been accepted for publication.

Sauermann and Leathwick are from AgResearch Grasslands in Palmerston North, New Zealand. Leathwick conceptualized the model, acquired the first funding and administered the project.  Sauermann organized the model and ran all simulations. Nielsen supervised the project.

The effect of climate, season, and treatment intensity on anthelmintic resistance in cyathostomins: A modelling exercise
Martin K. Nielsen, Christian W. Sauermann, Dave M. Leathwick
Veterinary Parasitology, Volume 269, May 2019, Pages 7-12, https://doi.org/10.1016/j.vetpar.2019.04.003