Anthelmintic resistance in nematodes of horses

Suppressive anthelmintic treatment strategies originally designed to control Strongylus vulgaris in horses were extremely successful in reducing morbidity and mortality from parasitic disease. Unfortunately, this strategy has inadvertently resulted in the selection of drug-resistant cyathostomes (Cyathostominea), which are now considered the principal parasitic pathogens of horses. Resistance in the cyathostomes to benzimidazole drugs is highly prevalent throughout the world, and resistance to pyrantel appears to be increasingly common. However, there are still no reports of ivermectin resistance in nematode parasites of horses despite 20 years of use. It is unknown why resistance to ivermectin has not yet emerged, but considering that ivermectin is the single most commonly used anthelmintic in horses most parasitologists agree that resistance is inevitable. The fecal egg count reduction test is considered the gold standard for clinical diagnosis of anthelmintic resistance in horses, but diagnosis is complicated by lack of an accepted standard for the performance of this test or for the analysis and interpretation of data. Presently there is very little data available on the molecular mechanisms of anthelmintic resistance in cyathostomes; beta-tubulin gene is the only anthelmintic-resistance associated gene that has been cloned. The increasingly high prevalence of anthelmintic-resistant cyathostomes must be taken into account when designing worm control programs for horses. Strategies to decelerate further selection for drug resistance thereby extending the lifetime of currently effective anthelmintics should be implemented whenever possible. Considering the nature of the equine industry in which horses often graze shared pastures with horses from diverse locations, transmission and widespread dispersal of resistant parasites is virtually assured. A proactive approach to this problem centered on understanding the molecular basis of anthelmintic resistance in cyathostomes is required if we are to expect chemical control of nematodes in horses to remain a viable element of parasite control in the future.     

Anthelmintic resistance in non-strongylid parasites of horses

Since 2002, selected populations of Parascaris equorum in several countries have been reported to survive treatment with macrocyclic lactone (M/L) anthelmintics. Clinical treatment failures are characterized by negligible fecal egg count reduction, but M/L resistance has been confirmed in ascarids by controlled efficacy testing. Resistance was selected by current parasite control practices for foals, which often include exclusive and excessively frequent use of M/L dewormers, thereby minimizing refugia within the host and in the environment. Chemical control of M/L-resistant isolates can be accomplished with pyrimidine and/or benzimidazole anthelmintics, but a few M/L-resistant populations have recently exhibited resistance to pyrantel pamoate as well. Some specimens of Oxyuris equi regularly survive treatment with macrocyclic lactones, but it is uncertain whether this constitutes resistance or merely confirms the incomplete oxyuricidal efficacy of virtually all broad spectrum equine anthelmintics. Variations in other biological parameters of Oxyuris and Parascaris, specifically atypical infection of older hosts and shorter prepatent periods, have been reported anecdotally. These changes may represent genetic modifications that have evolved in parallel with resistance as a result of anthelmintic selection pressure.     

Anthelmintic resistance

Extract

Recent local reports of nematodes resistant to anthelmintics should concern everyone involved with the livestock industries. The discovery, however, should come as no surprise. In a country that relies so heavily on anthelmintics for parasite control, it was inevitable that resistant nematodes would appear sooner or later.     

Anthelmintic treatment in horses: the extra-label use of products and the danger of under-dosing

Anthelmintic products form the basis of helminth control practices on horse stud farms at present. Regular evaluation of the efficacy of these products is advisable, as it will provide information on the worm egg reappearance period and the resistance status in the worm population. The aim of this study was to evaluate the efficacy of doramectin, pyrantel pamoate, ivermectin and moxidectin on a Thoroughbred stud farm in the Western Cape Province, South Africa. The study also compared the anthelmintic efficacy of two moxidectin formulations administered at their recommended dosages (an injectable, at 0.2 mg/kg, not registered for horses, and an oral gel at 0.4 mg/kg, registered for horses). Two mixed-sex groups of 30 yearlings and 40 weaners were tested in 2001 and 2002, respectively, divided into 3 and 4 groups of equal size. In 2001, moxidectin was one of 3 drugs administered orally and at a dose rate of 0.4 mg/kg. In 2002, pyrantel pamoate and ivermectin were orally administered at 19 and 0.2 mg/kg. Moxidectin and doramectin (the latter not registered for horses) were administered by intramuscular injection at a dose of 0.2 mg/kg, the dosage registered for other host species. The faecal egg count reduction test was used to determine the anthelmintic efficacies in both years. Each animal acted as its own control and the arithmetic mean faecal egg count and lower 95% confidence limit was calculated for each of the groups. A 100% reduction in the faecal egg counts and a 100% lower 95% confidence limit was recorded for moxidectin (0.4 mg/kg) in 2001. In 2002, a 99% and 96% reduction was recorded for pyrantel pamoate and ivermectin, respectively. In the same year doramectin and moxidectin (both injectable and given at 0.2 mg/kg) did not have any effect on worm egg counts. Of the 4 drugs tested in 2002, only pyrantel pamoate recorded lower 95% confidence limits above 90%.     

Anthelmintic resistance on goat farms in Georgia: efficacy of anthelmintics against gastrointestinal nematodes in two selected goat herds

Gastrointestinal nematode (GIN) parasitism is a major constraint to production of goats in the southeastern United States. The conventional method of control used by producers in this region is frequent use of anthelmintics during the warm season. Overuse of anthelmintics has led to an increase in the incidence of anthelmintic resistance in many parts of the world, but data on prevalence of anthelmintic resistance in GIN of goats in the southeastern United States are very limited. To address this issue, anthelmintic efficacy was determined in goat herds at the Fort Valley State University, Agricultural Research Station (FVSU-ARS) and the University of Georgia, College of Veterinary Medicine (UGA-CVM) using fecal egg count reduction (FECR) tests and DrenchRite((R)) larval development assays (LDA). At FVSU-ARS, 2-year-old Spanish goat does were randomly allocated to one of nine different treatment groups (n = 10): albendazole (ABZ; 20mg/kg body weight (BW)), fenbendazole (FBZ; 20mg/kg BW), ivermectin (IVM; 0.4 mg/kg BW), doramectin (DRM; 0.4 mg/kg BW), moxidectin (MOX; 0.4 mg/kg BW), levamisole (LEV; 12 mg/kg BW), morantel tartrate (MOR; 10mg/kg BW), a combination of IVM (0.4 mg/kg BW) and ABZ (20 mg/kg BW), and untreated controls. At UGA-CVM, goats were randomly allocated to one of five different treatment groups (n = 8): ABZ (20 mg/kg BW), IVM (0.4 mg/kg BW), MOX (0.4 mg/kg BW), LEV (12 mg/kg BW), and untreated controls. All drugs in both experiments were administered orally. Anthelmintic efficacy was calculated by comparing 14-day post-treatment FEC of treated and control animals, and percent reductions were interpreted using the World Association for the Advancement of Veterinary Parasitology guidelines for resistance. For the LDA, nematode eggs were isolated from pooled fecal samples of untreated control goats in each herd and used to perform DrenchRite((R)) assays. In the FVSU-ARS herd, MOX, LEV, the combination of IVM and ABZ, IVM, DRM, ABZ, MOR, and FBZ reduced FEC by 100, 91, 88, 78, 76, 62, 48, and 10%, respectively. In the UGA-CVM herd, MOX, LEV, ABZ and IVM, reduced FEC by 100, 94, 87, and 0%, respectively. In both herds moxidectin was the only drug tested that was fully effective. Results of the LDA were in agreement with results of the FECR tests for both herds. These data demonstrate the presence of GINs resistant to all three major anthelmintic classes in both goat herds.     

A field evaluation of anthelmintics in horses in Sweden

A field evaluation of anthelmintics in 336 horses on 37 farms was conducted between February and May 1986 in Sweden. The herds, each comprising at least eight horses, had histories of grazing on permanent pastures and receiving regular treatments against parasites at least three times a year. Small strongyles were refractory to (pro)-benzimidazole drugs in all but one of 23 herds examined. There was an average reduction in egg output of approximately 60%, and approximately 30% of 205 horses examined were shedding less than 100 eggs g-1 7 days after treatment. There was great between-herd variation of both the faecal egg-count depression (6.4-90.4%) and drug efficacy (0.0-80.0%). The non-benzimidazole drugs under investigation were fully effective against mature small strongyles.     

Anthelmintic resistance in cyathostomins of brood horses in Ukraine and influence of anthelmintic treatments on strongylid community structure

In 2004-2006, 322 brood horses from 11 horse farms were examined using the faecal egg count reduction test (FECRT) to determine the presence and distribution of anthelmintic resistance in strongylids in Ukraine. The anthelmintic drugs "Albendazole-7.5" (7.5mg of albenazole, Ukraine) at a dose of 5mg per kg body weight and "Univerm" (0.2% aversectin C, Russia) at a dose of 0.5mg per kg body weight were used. Seventy-one horses from six farms were examined in vivo to investigate the influence of anthelmintic treatment on the gastrointestinal strongylid community structure. Horses were treated with anthelmintics; faecal sampling (200 g in each sample) for strongylid expulsion was performed 24, 36, 48 and 60 h after treatment; and all strongylids expelled (25,292 specimens) were collected and identified. Fourteen horses from the Dubrovsky horse farm were also examined to determine the benzimidazole-resistant cyathostomin species; 5208 specimens of benzimidazole-resistant cyathostomins were collected and identified. According to the FECRT data, benzimidazole resistance in strongylids was observed only at the Dubrovsky horse farm (FECRT=68.7%). No resistance to macrocyclic lactones in strongylids or in Parascaris equorum was observed. Twenty-nine strongylid species were found in horses from six horse farms. The number of species per horse ranged from 4-9 (5.8+/-1.5) to 10-20 (14.4+/-2.9) and depended on horse anthelmintic treatment strategies. From 4 to 13 strongylid species predominated (prevalence>66.7%) in the strongylid community. Eleven cyathostomin species (Cylicocyclus nassatus, C. ashworthi, C. leptostomum, Cyathostomum catinatum, C. pateratum, Cylicostephanus calicatus, C. longibursatus, C. goldi, C. minutus, Coronocyclus coronatus and C. labiatus) were found to be resistant to benzimidazoles at the Dubrovsky horse farm. Ten of these were the dominant species in the strongylid community; only C. labiatus was a rare species (prevalence 29.4%). Species richness and species diversity were significantly higher in horses from farms without treatment or with occasional treatments than from farms with regular treatments. The shape of the prevalence frequency distribution of strongylid species from farms with regular treatments was bimodal ("core" and "satellite" mode). This distribution was multimodal at farms without treatment or with occasional anthelmintic treatments. The results of the current study indicated the possibility of the further spread of anthelmintic resistance on horse farms in Ukraine and the necessity of monitoring the development of resistance in horse parasitic nematodes.     

Anthelmintic resistance in New Zealand

Anthelmintic resistance was first confirmed in New Zealand in 1979 and since then has become common-place; more than 50 % of sheep farms now have detectable levels of resistance to one or more chemical classes of anthelmintic. Farmer drenching practices have changed little over the last 15–20 years and are clearly exerting a significant level of selection for resistance. In the absence of new chemical classes of anthelmintics, current parasite control practices will be unsustainable in the long-term. Once substantial resistance has developed, significant reversion to susceptibility is unlikely and re-introduction of failed drugs is likely to result in the rapid re-emergence of control problems. The number of anthelmintic treatments applied is not necessarily a reliable indicator of selection pressure and should not be the only factor considered in strategies for minimising the development of resistance. The relative potential of the different anthelmintics now available, particularly the long- acting products, to select for resistance varies with the way they are used and with other epidemiological and management factors; generalisations about their respective roles in the development of resistance are often unreliable. In many cases, literal extrapolation of recommendations for the management of resistance from Australia to New Zealand is unsupportable, given the differences in climate, parasite ecology and farming practices between the 2 countries. In the absence of a refuge for susceptible genotypes, as occurs when anthelmintic treatments are used as a means of generating low-contamination ‘safe’ pasture for young stock, the rapid development of resistance is likely. Anthelmintic treatments applied to animals with a high level of immunity, or which become immune while the anthelmintic is active, are likely to select for resistance faster than treatments applied to non-immune stock.