Pyrantel pamoate resistance in horses receiving daily administration of pyrantel tartrate

Emily L. Brazik Carolina Coastal Equine Veterinary Service, 1286 Hwy 117 N, Burgaw, NC 28425

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Jan T. Luquire Carolina Coastal Equine Veterinary Service, 1286 Hwy 117 N, Burgaw, NC 28425

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Dianne Little Carolina Colic and Digestive Disease Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606

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 BVSc, MS, DACVS

Abstract

Case Descriptions—16 horses treated daily with pyrantel tartrate (2.64 mg/kg [1.2 mg/lb], PO) as part of a prophylactic anthelmintic program.

Clinical Findings—Fecal worm egg counts (FWECs) were obtained on all 16 horses. Mean FWEC was 478 eggs/g (epg; range, 0 to 4,075 epg). Three of the 16 horses were responsible for 85% of the total fecal egg output for the herd on the day of sampling. Six horses had FWECs < 200 epg. Three horses that had arrived within 4 months of the sampling date had FWECs < 100 epg.

Treatment and Outcome—An FWEC reduction test was initiated the day after FWECs were obtained; all horses with FWECs > 100 epg (9 horses) were treated with pyrantel pamoate (6.6 mg/kg [3 mg/lb], PO), and 14 days later, the FWEC was repeated. During the 14-day period, all horses received pyrantel tartrate (2.64 mg/kg, PO) daily. Fecal worm egg count reduction was calculated for each horse. Mean FWEC reduction for the group was 28.5% (range, increase of 21% in FWECs 14 days after treatment to a decrease of 100% in FWEC 14 days after treatment).

Clinical Relevance—Farms should be monitored for cyathostomes resistant to pyrantel pamoate prior to use of pyrantel tartrate. Fecal worm egg counts should be monitored routinely in horses before and after treatment to ensure efficacy of cyathostome control measures.

Abstract

Case Descriptions—16 horses treated daily with pyrantel tartrate (2.64 mg/kg [1.2 mg/lb], PO) as part of a prophylactic anthelmintic program.

Clinical Findings—Fecal worm egg counts (FWECs) were obtained on all 16 horses. Mean FWEC was 478 eggs/g (epg; range, 0 to 4,075 epg). Three of the 16 horses were responsible for 85% of the total fecal egg output for the herd on the day of sampling. Six horses had FWECs < 200 epg. Three horses that had arrived within 4 months of the sampling date had FWECs < 100 epg.

Treatment and Outcome—An FWEC reduction test was initiated the day after FWECs were obtained; all horses with FWECs > 100 epg (9 horses) were treated with pyrantel pamoate (6.6 mg/kg [3 mg/lb], PO), and 14 days later, the FWEC was repeated. During the 14-day period, all horses received pyrantel tartrate (2.64 mg/kg, PO) daily. Fecal worm egg count reduction was calculated for each horse. Mean FWEC reduction for the group was 28.5% (range, increase of 21% in FWECs 14 days after treatment to a decrease of 100% in FWEC 14 days after treatment).

Clinical Relevance—Farms should be monitored for cyathostomes resistant to pyrantel pamoate prior to use of pyrantel tartrate. Fecal worm egg counts should be monitored routinely in horses before and after treatment to ensure efficacy of cyathostome control measures.

Effective control of strongyles, particularly cyathostomes, is becoming increasingly difficult in horses as anthelmintic resistance becomes more commonly recognized. Only 3 drug groups, the benzimidazoles, avermectins, and pyrantel salts, have efficacy against cyathostomes. Resistance to benzimidazoles is widespread, and resistance to pyrantel salts is becoming increasingly common, particularly in the southeastern United States.1 Resistance to macrocyclic lactones has not yet been reported. Daily administration of pyran-tel tartrate at a dosage of 2.64 mg/kg (1.2 mg/lb), PO, has been promoted as a means to control cyathostome infection in horses. However, there is concern that this practice may be associated with development of cyathostomes resistant to pyrantel pamoate administered at a dose of 6.6 mg/kg (3 mg/lb), PO.2 Findings of the report presented here confirm anthelmintic resistance to pyrantel pamoate administered at a dose of 6.6 mg/kg, PO, in adult horses that were treated with pyrantel tartrate administered prophylactically at a dosage of 2.64 mg/kg, PO, daily for at least 1 year.

As part of routine veterinary health care, FWECs of all horses were performed on a farm in which all horses living on the farm were treated daily with pyrantel tartrate (2.64 mg/kg, PO) as part of a prophylactic anthelmintic program. The prophylactic anthelmintic program had been in place for at least a year; however, the anthelmintic history prior to this time was not known. All horses had received ivermectin (200 μg/kg [91 μg/lb], PO, once) within the last 12 months, but records as to when this treatment had been given were not available from the farm manager. Horses were treated with pyrantel tartrate daily and ivermectin by the farm manager on the basis of estimated body weight; an accurate weight was not obtained for any horse. Sixteen horses of various ages (mean age, 10.1 years; range, 6 to 15 years), breeds (Thoroughbreds [n = 6]; Quarter Horses [3], Thoroughbred crosses [2]; Mustangs [2]; and 1 each of Welsh Cross, pony, and Warmblood), and sexes (14 geldings and 2 mares) lived on the farm. Three horses had arrived on the farm during the preceding 4 months. For part of the day, horses had access to 1 of 5 small paddocks in groups of 2 or 3, with several horses moving regularly between pastures. Feces were not removed from pastures, and pastures were not harrowed on a regular basis.

Fecal worm egg counts were obtained for all 16 horses by use of the McMaster technique with a lower limit of sensitivity of 25 epg. Mean FWEC was 478 epg (range, 0 to 4,075 epg). Three of the 16 horses were responsible for 85% of the total fecal egg output for the herd on the day of sampling. Six of the 16 horses had FWECs <200 epg. All 3 horses that had arrived within 4 months of the sampling date had FWECs <100 epg. The next day, an FWECRT was initiated; all horses with FWECs >100 epg (9 horses) were treated with pyrantel pamoate (6.6 mg/kg, PO), and 14 days later, the FWEC was repeated. During this 14-day period, all horses received pyrantel tartrate (2.64 mg/kg, PO) daily. Fecal worm egg count reduction was calculated for each horse by use of the following formula:

article image

Results of FWECRT for the 9 horses with FWECs >100 epg are depicted (Table 1). Mean FWEC reduction for the group was 28.5% (range, increase of 21% in FWECs 14 days after treatment to a decrease of 100% in FWEC 14 days after treatment).

Table 1—

Results of initial FWECs during daily treatment with pyrantel tartrate (2.64 mg/kg [1.2 mg/lb], PO) and results of FWECRT 14 days after treatment with pyrantel pamoate (6.6 mg/kg [3 mg/lb], PO), which was administered to 9 horses with initial FWECs > 100 epg.

Initial FWEC (epg)FWECRT
4,07536% decrease
20025% decrease
1750% decrease
92521% increase
1,5008% decrease
2759% increase
125100% decrease
27518% decrease
100100% decrease

Results expressed as percentage increase or decrease from initial FWEC.

Prophylactic use of pyrantel tartrate daily was discontinued on the farm after the inefficacy of the control program was demonstrated. The 3 horses with the highest FWEC before treatment were treated with fenbendazole (10 mg/kg [4.5 mg/lb], PO) once daily for 5 days, and then ivermectin (200 μg/kg, PO) was administered on day 6. Fecal worm egg counts were obtained every 2 months for all horses, and horses were treated selectively with ivermectin if the FWEC was >200 epg. Additionally, every horse was treated once yearly with pyrantel pamoate (13.2 mg/kg [6 mg/lb], PO) for Anoplocephala perfoliata.

Discussion

On the farm of this report, pyrantel tartrate administered at a dosage of 2.64 mg/kg, PO, daily did not adequately control fecal egg output in mature horses. Additionally, strongyles resistant to pyrantel pamoate were identified in 7 of the 9 horses tested. Whether this drug resistance was evident prior to initiation of pyran-tel tartrate treatment or whether it was induced by use of pyrantel tartrate cannot be determined. However, daily administration of pyrantel tartrate was clearly inadequate for prophylactic control of strongyles on the farm. On the farm of this report, cyathostomes resistant to pyrantel tartrate were only detected because a monitoring program was instituted. If such a program had not been implemented, it is expected that cyathostome populations on the farm would have escalated to the point in which clinical larval cyathostomiasis would have been identified in some horses living on the farm, as has been reported previously when a case of larval cyathostomiasis prompted investigation of cyathostome drug resistance and identification of cyathostome populations resistant to both fenbendazole and pyrantel pamoate.3

Cyathostomes resistant to pyrantel have been described in the southeastern United States and in Europe.2 Reportedly, in the United States, the prevalence of pyrantel pamoate resistance is 20% to 40% in Georgia,2,4 and on 33% of farms evaluated in Florida, pyrantel pamoate resistance has been detected.5 Resistance to pyrantel pamoate has also been reported in Louisiana.6 The mechanism of resistance to pyrantel pamoate appears to be a mutation of the nicotinic acetylcholine receptor.7 In Georgia, on some farms in which resistance to pyrantel pamoate has been reported, there was a history of daily administration of pyran-tel tartrate, suggesting that cross-resistance may develop.2,4 Pyrantel tartrate administered daily at a dosage of 2.64 mg/kg, PO, is marketed for control of recently ingested third-stage larvae, and both pyrantel tartrate and pyrantel pamoate administered at a dose of 6.6 mg/kg, PO, are effective against fourth-stage luminal and adult cyathostomes. Neither drug has efficacy against encysted cyathostomes.8,9

On the farm of this report, the distribution of parasite load among horses (3 of 16 [18.7%] of horses responsible for 85% of the total egg output) is consistent with the situation in most host-parasite interactions, in which approximately 20% of the hosts contribute approximately 80% of the parasite load10; this distribution did not appear to have been altered by daily administration of pyrantel tartrate. An FWECRT for benzimidazole or ivermectin resistance was not performed on the farm of this report for financial reasons, but benzimidazole resistance was assumed to be present, and ivermectin resistance was not assumed to be present, given that in the United States, benzimidazole resistance is generally assumed to be widespread, but ivermectin resistance has not yet been reported.1 Given the concern regarding development of ivermectin resistance, egg reappearance times and FWECRT for ivermectin are being monitored on this farm. The selective use of an anthelmintic such as ivermectin, to which resistance has not yet been reported, in horses with FWEC >200 epg on this farm should decrease selection pressure for resistance by permitting a proportion of cyathostomes to remain unexposed to ivermectin and by decreasing the frequency at which cyathostome populations are exposed to the drug.4,11,12

On the basis of our findings, before use of pyran-tel tartrate can be recommended for use on an individual farm, we recommend that all horses undergo an FWECRT for detection of cyathostomes resistant to pyrantel pamoate. Furthermore, we recommend that FWEC be performed for all horses twice yearly to monitor for development of resistance to pyrantel tartrate and, if failure of treatment efficacy on the farm is detected by FWEC, that the use of pyrantel tartrate be discontinued. As part of any monitoring program, pasture and farm management practices should be evaluated to determine if improvements can be made that will decrease selection pressure for development of resistance and the level of pasture contamination with cyathostomes. The efficacy of benzimidazoles and avermectins should be evaluated by FWECRT, and egg reappearance times should be monitored for avermectins. A cyathostome control program based on selective treatment of individual horses should be initiated to decrease the risk of clinical disease in individual horses and the risk of development of cyathostomes resistant to other drug classes on the farm. Failure to monitor FWEC in horses treated daily with pyrantel tartrate may result in failure to detect cyathostomes resistant to pyrantel salts; breakdown of the control program in place on the farm; and, ultimately, subclinical or moderate to severe clinical signs of cyathostomiasis in individual horses caused by high cyathostome burdens.

FWEC

Fecal worm egg count

epg

Eggs per gram

FWECRT

FWEC reduction test

References

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