Phenothiazine in the origin of benzimidazole resistance in population-B equine strongyles

Clinical trials on a central Kentucky Thoroughbred Farm (B) during 1960-1961 involved nine test treatments of mares, yearlings and weanlings (n = 124), and compared efficacies of phenothiazine (PTZ), piperazine (PPZ), mixtures of PTZ + PPZ and thiabendazole (TBZ) for (1) percent reduction and (2) complete clearance or graded reduction of strongyle egg per gram (epg) counts. Three grades of PTZ (N.F. green, micronized purified and 2-3 microns purified) at the dose rate of 55 mg kg-1 were ineffective in six tests; reduction of strongyle epg count were low grade (26%) and complete clearance was found in only 1 of 32 horses. Piperazine alone at 88 mg base kg-1 was efficacious in two tests; epg counts were effectively reduced (98%), but complete clearance was found in only 2 of 10 horses. Several mixtures of PTZ + PPZ with various dosages of PTZ (27.5-55 mg kg-1) plus PPZ base (88 mg kg-1) were quite effective in six tests, as epg counts were reduced by 96% and complete clearance occurred in 25 of 38 horses. Four trials with TBZ at dose rates between 13 and 44 mg kg-1 in 1961 reduced epg counts by 98%, but cleared only 15 of 36 horses. These data indicated: (1) a large segment of the Farm B small strongyle population was resistant to PTZ at the outset of these observations in 1960; (2) TBZ-resistant individuals were also present in this population when TBZ was first used in 1961. During the ensuing 4-year study (1962-1965) on Farm B mares (n = 15 per year) and yearlings (n = 15-17 per year), biweekly epg and larvae per gram (lpg) counts were carried out to compare the efficacy of three treatment programs: (1) monthly doses of TBZ at 26 mg kg-1; (2) monthly doses of TBZ at 13 mg kg-1; (3) bimonthly doses of a mixture of PTZ + PPZ and carbon disulfide (CS2) at dose rates of 27.5 + 88 and 78 mg kg-1, respectively, or a mixture of PTZ + PPZ + trichlorfon (TCF) at dose rates of 27.5 + 88 + 40 mg kg-1, respectively. Emergence of a TBZ-resistant segment of the small strongyle infections was evaluated by three criteria: (1) annual mean strongyle epg counts; (2) efficacy of individual treatments for epg reductions (%); (3) complete clearance or graded reductions of strongyle epg counts.4+ PTZ-resistant small strongyles. Initial use of TBZ in 1961 produced effective epg reductions, but complete clearance data revealed the presence of TBZ-resistant small strongyles at the outset...     

Benzimidazole resistance of equine strongyles: critical tests of several classes of compounds against population B strongyles from 1977 to 1981

From 1977 to 1981, critical tests were conducted on 10 horses naturally infected with population B strongyles. Drugs tested were: oxibendazole (OBZ), 10 mg/kg of body weight (n = 1); albendazole, 10 mg/kg (n = 1); a mixture of thiabendazole (TBZ), 44 mg/kg and trichlorfon, 40 mg/kg (n = 1); a mixture of TBZ at 44 mg/kg with piperazine (PPZ) at 55 mg of base/kg (n = 1); febantel (FBT), 6 mg/kg (n = 3), 12 mg/kg (n = 1), or 24 mg/kg (n = 1); and pyrantel (PRT) pamoate, 6.6 mg of base/kg (n = 1). Large strongyles, Strongylus vulgaris (9 horses) and S edentatus (5 horses), were effectively removed (100%) by each compound and mixture. Five species of small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus), previously singled out in this population as resistant to 5 benzimidazoles (TBZ, mebendazole, cambendazole, fenbendazole, and oxfendazole), but not OBZ, were efficaciously removed by OBZ, albendazole, the mixture of TBZ plus PPZ, FBT (24 mg/kg), or PRT. These 5 small strongyle species were resistant to FBT (6 mg/kg) in 3 foals and Cylicostephanus minutus was also resistant in 2 of 3 foals to FBT (6 mg/kg). Doubling the dose of FBT to 12 mg/kg increased the average removal of the 5 basic species plus Cylicostephanus minutus to 88%. The mixture of TBZ and trichlorfon was relatively ineffective against 3 species (C catinatum, C coronatum, and Cylicostephanus longibursatus), but unexpectedly efficacious (86% to 99%) for 2 species (Cylicocyclus nassatus and Cylicostephanus goldi).(ABSTRACT TRUNCATED AT 250 WORDS)     

Parasites in Kentucky Thoroughbreds at necropsy: emphasis on stomach worms and tapeworms

A total of 363 Thoroughbreds (62 males, 292 females, and 9 geldings), 1 to 26 years of age, were examined at necropsy for internal parasites for about a 12-month period from February 1981 through February 1982. Emphasis was on examining the stomach for nematodes and the small intestine and cecum for tapeworms. Parasites recovered from the stomach and infection rates were: Habronema spp--immature (24%), H muscae--adult (38%), Draschia megastoma--immature (13%), D megastoma--adult (62%), and Trichostrongylus axei--adult (4%); lesions caused by D megastoma were found upon gross observation in 58% of the stomachs. The tapeworm, Anoplocephala perfoliata, was recovered from 54% of the horses; A magna was not found. There was no obvious difference in infection rates of the stomach worms and tapeworms according to age or sex of the horses. Seasonal differences were apparent only for immature Habronema spp and immature D megastoma for which infection rates began increasing in June, peaking in October, and declining thereafter. Presence of 4 additional species of parasites was recorded, but only a cursory examination was made for them. These were the large strongyles, Strongylus vulgaris, S edentatus, and S equinus, from the cecum and a filariid, Setaria spp (probably S equina), from the abdominal cavity, for which recovery rates from the horses were 8%, 8%, 1%, and 7%, respectively.     

Development of free-living stages of equine strongyles in faeces on pasture in a tropical environment

The development of the free-living stages and yields of infective third stage strongyle larvae in faeces from a horse with a mixed natural infection deposited on pasture plots were studied over a 2-year period in a coastal area in tropical north Queensland. Two sets of faecal masses (one exposed to, and the other protected from the action of a natural population of dung beetles) were deposited monthly and after 7 days faecal samples were taken for larval recovery and counts. Hatching and development of the free-living stages occurred in faeces on pasture throughout the year. Development was rapid as infective stages were reached within a week of faecal deposition in all months. Yields of infective larvae were affected by the season and the action of dung beetles on the faecal masses. Highest yields were obtained from both beetle-exposed and protected faeces during winter (June to August) and lowest yields were in spring (September to November). High temperatures in spring and summer resulted in low yields of larvae, however, the dry conditions in spring made this season the most unfavourable period. In autumn and winter the temperatures were never low enough to stop or markedly slow down the rate of development, and allowed the development of large numbers of infective larvae. Dung beetle activity was observed throughout the year, and exposed faeces were usually completely dispersed within 24 h of deposition. This resulted in lower yields of infective larvae from these than from protected faeces. Though larval yields were lower, the actual numbers were still substantial so as to cast doubt on the usefulness of these beetles as biological control agents for equine strongylosis in the dry tropics.     

Disease patterns in the Detroit Zoo: a study of the mammalian population from 1973 through 1983

A retrospective study was conducted to evaluate disease patterns in the mammals at the Detroit Zoo from 1973 through 1983. The reindeer (Rangifer tarandus), common eland (Taurotragus oryx), rednecked Wallaby (Protemnodon rufogrisea), sitatunga (Tragelaphus spekii), and kangaroo (Macropus spp)- were the most frequently affected mammalian species. Parasitic agents (80% of which were internal parasites) caused morbidity in 60.2% of the mammals evaluated (n = 2,475) and microbial agents caused morbidity in 20.8% of the animals. Strongyloides spp, Trichostrongylus spp, coccidian species, Diphyllobothrium spp, and Trichuris spp were the internal parasites most frequently found. Overall annual mortality rate was 14% to 34%, with microbiological agents causing the highest mortality (26.5%). Pasteurella spp, beta-hemolytic Streptococcus spp, pathogenic Escherichia coli, Corynebacterium spp, and Klebsiella pneumoniae were the most frequent microbial causes of death. Cause of mortality could not be determined in 21.5% of the animals evaluated. The percentage of animals successfully treated increased from 1973 through 1983. Generally, however, the percentage of successfully treated animals was low (21% to 39%).     

Disease patterns in the Detroit Zoo: a study of the avian population from 1973 through 1983

A retrospective study was conducted to evaluate disease patterns in birds at the Detroit Zoo from 1973 through 1983. Data were derived from the zoo's medical and animal census records; the mean (+/- SD) population of birds during the study period was 469 +/- 42. Overall annual morbidity rates were 12.5% to 21.5%, with spring months having the highest morbidity rates. Annual mortality rates were 3.1% to 15.2%; 23.9% of the deaths were caused by microbial agents (particularly Erysipelothrix rhusiopathiae, hemolytic Escherichia coli, Salmonella spp, Aeromonas spp and Proteus spp), 15.4% by trauma, and 42.5% by nondetermined causes. The mute swan (Cygnus olor), mallard duck (Anas platyrhynchos), common gallinule (Gallinula chloropus), common rhea (Rhea americana), and red-billed hornbill (Tockus erythrorhynchus) were the 5 species most frequently affected of the 1,032 deaths from 1973 through 1983. The most frequently isolated parasites were Microtetramere spp, coccidian species, Diplotriaena spp, and Trichomonia spp.     

Prevalence of Anoplocephala perfoliata and lesions of Draschia megastoma in Thoroughbreds in Kentucky at necropsy

A total of 396 Thoroughbreds (86 males, 293 females, and 17 geldings) in Kentucky, 1 to 30 years of age, were examined at necropsy for presence of Anoplocephala perfoliata (2 female horses were not examined) in the cecum for lesions of Draschia megastoma in the stomach, during the 1-year period of Mar 1, 1982 through Feb 28, 1983. Prevalence of A perfoliata was 53% and of lesions of D megastoma was 63%. All lesions of D megastoma were partially or entirely in the glandular region of the stomach. Distances of the midpoint of these lesions from the margo plicatus varied from 0 to 290 mm. The center of about 88% of the lesions was within 50 mm of the margo plicatus . Measurements of the size of the lesions, exclusive of masses, indicated that about 95% were less than or equal to 50 mm in diameter. There appeared to be a higher infection rate of lesions of D megastoma in younger horses (81% in 1 to 7 year olds) than in older horses (41% in 8 to 30 year olds) with a few exceptions.     

Disease patterns in the Detroit Zoo: a study of reptilian and amphibian populations from 1973 through 1983

A retrospective study was conducted to determine disease patterns in reptilian and amphibian populations at the Detroit Zoo from 1973 through 1983. In the reptilian population (mean +/- SD = 285.2 +/- 28), overall annual mortality rates were 1% to 40%. Mortality rates were highest in the fall months (20%) and lowest in the winter months (6%). The most frequently affected reptiles were iguana (Iguana iguana), reticulated python (Python reticulatus), rattlesnakes (Crotalus spp), common boa (Constrictor constrictor), and lizards (various genera of suborder Lacertilia). Of the 1,300 reptilian deaths from 1973 through 1983, 36.6% were caused by microbial agents, 12% by parasites, 11.6% by trauma, and 9.3% by nutritional deficiencies. The main microbial organisms that caused death were Aeromonas spp, Salmonella spp, Pseudomonas spp, Proteus spp, and Edwardsiella spp. The main parasites that caused death were Entamoeba spp and lungworms. Among amphibians, frogs and toads were the most frequently affected, and starvation and trauma were the most frequent causes of death.     

Climatic influences on development and survival of free-living stages of equine strongyles: implications for worm control strategies and managing anthelmintic resistance

Development of resistance to anthelmintic drugs by horse strongyles constitutes a growing threat to equine health because it is unknown when new drug classes can be expected on the market. Consequently, parasite control strategies should attempt to maintain drug efficacy for as long as possible. The proportion of a parasite population that is not exposed to anthelmintic treatment is described as being "in refugia" and although many factors affect the rate at which resistance develops, levels of refugia are considered the most important as these parasites are not selected by treatment and so provide a pool of sensitive genes in the population. Accordingly, treatment should be avoided when pasture refugia are small because such treatments will place significant selection pressure for resistance on worm populations. Given this new paradigm for parasite control, it has become important to identify seasons and circumstances wherein refugia are diminished. Free-living stages of equine strongyles are highly dependent on climatic influences, and this review summarises studies of strongyle development and survival under laboratory and field conditions in Northern (cool) temperate, Southern (warm) temperate and subtropical/tropical climates. In Northern temperate climates, refugia are smallest during the winter. In contrast, refugia are lowest during the summer in warm temperate and subtropical/tropical climates. Although adverse seasonal changes clearly have significant effects on the ability of free living stages of strongyle nematode parasites to survive and develop, available data suggest that climatic influences cannot effectively "clean" pastures from one grazing season to the next.     

Possible resistance of small strongyles from female ponies in The Netherlands against albendazole

To determine resistance of small strongyles to albendazole, 3 female ponies (group 1) were grazed on a pasture from May to November 1985 and were treated with 7.5 mg of albendazole/kg of body weight, PO, 2 days before turnout in May and again in June and in July. Three other female ponies (group 2) grazed on a similar pasture from May to July, were treated with 7.5 mg of albendazole/kg, and were removed to another pasture until November. In December, ponies from both groups were treated with 7.5 mg of albendazole/kg, and 8 days later, they were euthanatized and necropsied for a critical test. Worm egg counts in the ponies' feces revealed that the May treatment of group 1 and the July treatment of group 2 were more effective than were later treatments. Numbers of small strongyles were higher in group 1 than in group 2. Efficacy of treatment against all developmental stages of small strongyles was higher in group 2 than in group 1. Efficacy was low in both groups against parasitic 3rd- and 4th-stage larvae. Fifteen species of small strongyles were identified at necropsy. Efficacy was limited against adult Cyathostomum coronatum, Cya labratum, Cylicostephanus calicatus, and Cyl poculatus in both groups; Cylicocyclus nassatus, Cyl minutus, and Cyl longibursatus in group 1; and Cya labiatum in group 2. Efficacy was 100% against Cya catinatum, Cyl goldi, and 5 other species that were found in low numbers.     

Determining the endpoint of an outbreak of equine influenza in a large population of racing Thoroughbreds

Outbreaks of equine influenza (EI) cause major disruption to the racing industry, resulting in cessation of racing until affected horses have recovered from the disease. The introduction of EI to a large population of Thoroughbred horses stabled at a Sydney racecourse provided the opportunity to observe clinical signs and monitor the spread of EI in this predominantly na?ve population and to assist in determining an endpoint to infection spread to allow resumption of racing events.     

Prevalence,abundance and site distribution of equine small strongyles in Normandy,France

Forty-two horses from Normandy (France) were examined post-mortem for small strongyle infections from October to March. In the positive horses, total worm numbers ranged from 234 to 90,247 (mean 11,297). Encysted larvae represented the major part of the total cyathostome burdens with a high percentage (83%) being early third stage larvae. They were mostly recovered from the caecum (48%) and ventral colon (40%) and were less present in the dorsal colon (12%). Adult cyathostomes were mainly located in the ventral colon (64%) and less frequently in the dorsal colon (27%) and caecum (9%). Twenty species of Cyathostominae were identified. The 10 most prevalent species (in sequence of prevalence) were Cyathostomum coronatum, Cylicocyclus nassatus, Cylicocyclus insigne, Cyathostomum catinatum, Cylicostephanus goldi, Poteriostomum imparidentatum, Cyathostomum labiatum, Cylicocyclus ultrajectinus, Cylicostephanus calicatus and Cylicostephanus minutus which comprised 84% of the total adult population. Twelve species showed a site preference in the ventral colon, five in the dorsal colon and only one in the caecum while two species were collected in nearly equal numbers from the ventral and dorsal colon. The number of species per horse ranged from 1 to 12 with a median of 5. Infections with singletons occurred in 12.5% of the positive horses while multiple infections were encountered in 87.5%. A positive correlation was found between the intensity of cyathostome infection and its diversity, measured either by the number of occurring species or Shanon indexes.     

Insulin resistance in equine digital vessel rings: an in vitro model to study vascular dysfunction in equine laminitis

Reasons for performing study: One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels. Hypothesis and objectives: Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies. Methods: Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at 37°C, 2 g tension was applied and the rings allowed to equilibrate for 45 min. Of the 4 rings of each vessel type, one was used as a control. One each of the remaining 3 rings was used for incubation with insulin (to induce resistance), wortmannin (to block PI3‐kinase) and PD‐098059 (to block MAP‐kinase), respectively, for 30 min. After the incubation period, the rings were contracted with phenylephrine. When the response reached a plateau, a single dose of insulin was added to the baths and the response of each ring monitored for 30 min. Results: Insulin relaxed the control rings and those treated with PD 098059 but contracted those pretreated with insulin and wortmannin. Normal relaxation responses of the rings were converted to contractions by insulin resistance. Insulin resistance was confirmed by the qualitative response of insulin‐incubated and wortmannin‐incubated rings. Conclusions: This study demonstrated successful induction of insulin resistance in both arterial and venous rings. It also suggested that the MAP‐kinase pathway plays a minor role in controlling vasomotor tone under normal physiological conditions. Potential relevance: The study suggests that the induction of insulin resistance in equine palmar digital vessel rings is reliable and provides a good in vitro model for studying the vascular insulin resistance which may occur in equine laminitis.     

Continuance of studies on Population S benzimidazole-resistant small strongyles in a Shetland pony herd in Kentucky: effect of pyrantel pamoate (1992-1999)

Research on benzimidazole-resistant Population S small strongyles began in a Shetland pony herd in 1974 at the University of Kentucky and has continued for over 25 years. The present update, for the period 1992-1999, evaluated activity of pyrantel pamoate (PRT) in field tests in the pony herd. Additional critical tests with PRT and oxibendazole (OBZ) were done in foals born in the herd. Activity of PRT was initially excellent in field tests, based on epg/lpg count data, but declined rapidly during the second full year of pyrantel treatments. Critical test data for small strongyles indicated efficacies of PRT were about 60% at the beginning of the present observations and this intermediate level of removal continued throughout the seven-year period except for 1994 (75%). Unusual was the finding that field test epg/lpg data on small strongyles indicated much lower activity of PRT than found in worm count data in critical tests. The previously reported ineffective activity of OBZ on this population of small strongyles continued. Data are presented on prevalence and drug activity on several species of internal parasites besides small strongyles.