Local and systemic inflammatory and immunologic reactions to cyathostomin larvicidal therapy in horses.

Encysted cyathostomin larvae are ubiquitous in grazing horses. Arrested development occurs in this population and can lead to an accumulation of encysted larvae. Large numbers of tissue larvae place the horse at risk for developing larval cyathostominosis. This disease complex is caused by mass emergence of these larvae and is characterized by a generalized acute typhlocolitis and manifests itself as a profuse protein-losing watery diarrhea with a reported case-fatality rate of about 50%. Two anthelmintic formulations have a label claim for larvicidal therapy of these encysted stages; moxidectin and a five-day regimen of fenbendazole. There is limited knowledge about inflammatory and immunologic reactions to larvicidal therapy. This study was designed to evaluate blood acute phase reactants as well as gene expression of pro-inflammatory cytokines, both locally in the large intestinal walls and systemically. Further, mucosal tissue samples were evaluated histopathologically as well as analyzed for gene expression of pro- and anti-inflammatory cytokines, cluster of differentiation (CD) cell surface proteins, and select transcription factors. Eighteen juvenile horses with naturally acquired cyathostomin infections were randomly assigned to three treatment groups; one group served as untreated controls (Group 1), one received a five-day regimen of fenbendazole (10mg/kg) (Group 2), and one group received moxidectin (0.4mg/kg) (Group 3). Horses were treated on day 0 and euthanatized on days 18-20. Serum and whole blood samples were collected on days 0, 5, and 18. All horses underwent necropsy with collection of tissue samples from the ventral colon and cecum. Acute phase reactants measured included serum amyloid A, iron and fibrinogen, and the cytokines evaluated included interferon γ, tumor necrosis factor α, transforming growth factor (TGF)-ß, and interleukins 1ß, 4, 5, 6, and 10. Transcription factors evaluated were FoxP3, GATA3 and tBet, and CD markers included CD163, CD3z, CD4, CD40, and CD8b. Histopathology revealed an inflammatory reaction with higher levels of lymphocytes, T cells, B cells, eosinophils and fibrous tissue in the moxidectin-treated group compared to controls or horses treated with fenbendazole. No apparent systemic reactions were observed. Expression of IL-5 and TGF-ß in intestinal tissues was significantly lower in Group 3 compared to Group 1. This study revealed a subtle inflammatory reaction to moxidectin, which is unlikely to cause clinical issues.

Comparison of the larvicidal efficacies of moxidectin or a five-day regimen of fenbendazole in horses harboring cyathostomin populations resistant to the adulticidal dosage of fenbendazole.

Despite widespread acknowledgement of cyathostomin resistance to adult icidal dosages of benzimidazole (BZD) anthelmintics, many strongyle control programs continue to feature regularly scheduled larvicidal treatment with fenbendazole (FBZ). However, no studies have been conducted to evaluate the efficacy of larvicidal regimens against encysted cyathostomins in a BZD-resistant (BZD-R) population. A masked, randomized, controlled clinical study was conducted with 18 juvenile horses harboring populations of cyathostomins that were considered BZD-R on the basis of fecal egg count reduction (FECR). Horses were blocked by prior history, ranked by egg counts, and allocated randomly to one of three treatment groups: 1--control, 2--FBZ >10mg/kg once daily for five consecutive days, or 3--moxidectin (MOX) >0.4 mg/kg once. Fecal samples were collected prior to treatment and seven and 14 days after the final dose of anthelmintic. On Days 18-20, complete replicates of horses were euthanatized and necropsied, and 1% aliquots of large intestinal contents were recovered for determination of complete worm counts. The cecum and ventral colon were weighed, and measured proportions of the respective organ walls were processed for quantitation and characterization of encysted cyathostomin populations. The five-day regimen of FBZ achieved 44.6% fecal egg count reduction, had 56.4% activity against luminal adults and larvae, and was 38.6% and 71.2% effective against encysted early third stage (EL3) and late third stage/ fourth stage (LL3/L4) cyathostomin larvae, respectively. In contrast, MOX provided 99.9% FECR, removed 99.8% of luminal stages, and exhibited 63.6% and 85.2% efficacy against EL3 and LL3/L4 mucosal cyathostomins, respectively. Although BZD-R was the most feasible explanation for the lower larvicidal efficacies of FBZ, mean larval counts of moxidectin-treated horses were not significantly different from controls or those treated with FBZ. The lack of significant differences between larvicidal treatments was partially attributed to a small sample size and high variability among worm burdens. Historical differences in the time intervals between treatment and necropsy were identified as a confounding factor for accurate estimation of larvicidal efficacy. Determining appropriate post-treatment intervals for measuring larvicidal efficacy remains a critical regulatory and scientific challenge for this therapeutic area.

Effects of daily pyrantel tartrate on strongylid population dynamics and performance parameters of young horses repeatedly infected with cyathostomins and Strongylus vulgaris.

Strongylid infections are ubiquitous in grazing horse populations. Infections with cyathostomin (small strongyle) and strongylin (large strongyle) nematodes have long been associated with clinical disease in horses, but little is known about their subclinical impact. A masked, randomized, controlled study was conducted to evaluate the effects of daily administration of pyrantel tartrate on body condition scores, weight gain, fecal egg counts, and total worm counts of young horses repeatedly inoculated with strongylid larvae. Twenty eight immature horses were treated with larvicidal anthelmintic regimens and randomly allocated to two groups. Group 1 horses were given a pelleted placebo product once daily, and those in Group 2 received pyrantel tartrate once daily at ∼ 2.64 mg/kg body weight. On five days during each week, ∼ 5000 infective cyathostomin larvae were administered to each horse. In addition, horses received ∼ 25 infective Strongylus vulgaris larvae once weekly. Horses were maintained on pasture for 154 days and had ad libitum access to grass hay throughout. At approximate, 14-day intervals, body weights were measured, body condition scores were assigned, fecal samples were collected for egg counts, and blood samples were collected for measurement of S. vulgaris antibodies and various physiologic parameters. After 22 weeks at pasture and 14-17 days in confinement, horses were euthanatized and necropsied. Nematodes were recovered and counted from aliquots of organ contents, representative samples of large intestinal mucosa, and the root of the cranial mesenteric artery. Daily treatment with pyrantel tartrate at the recommended dosage significantly reduced numbers of adult cyathostomins in the gut lumen and early third-stage larvae in the cecal mucosa, increased the proportions of fourth-stage larvae in the gut contents, and was accompanied by significant improvements in body condition scores. Fecal egg counts of horses receiving daily pyrantel tartrate were significantly reduced, with percentages of efficacy ranging from 84.4% to 98.9%, but egg counts of both groups increased significantly over the course of the study. Treatment also significantly reduced the numbers of S. vulgaris larvae in the cranial mesenteric artery by 99.2%. Serum antibodies to S. vulgaris apparently persisted from pre-enrollment infections, but ELISA values gradually declined over the course of the study. This study has provided useful insights into the effects of daily pyrantel tartrate on the dynamics of cyathostomin infection, and into some subclinical effects of strongylid parasitism in horses.

Physiologic and systemic acute phase inflammatory responses in young horses repeatedly infected with cyathostomins and Strongylus vulgaris.

Migrating Strongylus vulgaris and encysted cyathostomin larvae cause a localized inflammatory response in horses. It is unknown whether these larvae elicit a systemic acute phase response (APR), evidenced by changes in serum amyloid A (SAA), haptoglobin (Hp), iron (Fe), albumin, or albumin/globulin (A/G) ratio. In this study, 28 horses were randomly allocated to receive either pyrantel tartrate or a pelleted placebo formulation in their daily feed. Concurrent with treatment, all the horses were administered 5000 pyrantel-susceptible cyathostomin infective larvae once daily, 5 days a week, for 24 weeks. Beginning in the fifth week, the horses also received 25 S. vulgaris larvae once weekly for the remainder of the study. At regular biweekly intervals, fecal samples were collected for quantitative egg counts, and whole blood and serum samples were collected for measurement of packed cell volume, total protein, albumin, globulin, A/G ratio, SAA, Hp, and Fe. On days 161-164, all the horses were euthanatized and necropsied. Samples were collected for enumeration of total luminal worm burdens, encysted cyathostomin larval populations, and migrating S. vulgaris larvae. Concentrations of Hp, Fe, and A/G ratio were associated significantly with strongyle burdens. Only treated male horses had significant increases in serum albumin. Larval S. vulgaris did not associate with Fe, whereas Fe was associated negatively with both total cyathostomin burdens and encysted L4s. The A/G ratios differed significantly between the two treatment groups. Significant differences between groups and individual time points were also observed for Hp and Fe, whereas SAA concentrations remained low throughout the study. In general, this study illustrated that experimental inoculations with S. vulgaris and cyathostomins may be associated with changes in Hp, Fe, and serum proteins, but not with SAA. Overall, these changes suggest that mixed strongyle infections elicit a mild acute phase reaction.

Anthelmintic resistance in equine parasites--current evidence and knowledge gaps.

Anthelmintic resistance is becoming increasingly prevalent among equine nematode parasites. The first reports documenting resistance were published in the 1960s, just a short time after introduction of the first modern anthelmintics phenothiazine and thiabendazole. Several factors are known to influence development of resistance, but evidence specific to equine parasites is limited. Most current knowledge and applications have been extrapolated from research with trichostrongylid parasites of sheep. The number of cyathostomin species co-infecting horses adds to the complexity of investigating drug resistance but, given their apparent limited biological diversity, viewing these in a unispecific context remains a pragmatic approach. Factors affecting resistance development in cyathostomins include parasite seasonality, life span and fecundity, host immunity, and the existence of encysted stages. Further, parasite refugia have been shown to play a vital role in resistance development in other parasites, and likely is also important in equine parasites. Specific genetic factors for drug resistance and possible modes of inheritance have been identified for trichostrongylid nematodes, but it is widely accepted that several more remain undiscovered. Current evidence with equine and ruminant parasites suggests that fitness is not significantly compromised in drug resistant strains. Attempts to develop in vitro and molecular assays for diagnosing anthelmintic resistance in equine nematodes have had only limited success, standardized guidelines are sorely needed for performing the fecal egg count reduction test in horse populations. Taken together, this review illustrates the complexity of understanding anthelmintic resistance in equine nematodes, and emphasizes the need for further research.

Herding the U.S. cattle industry toward a paradigm shift in parasite control.

Contemporary management of nematode parasitism in cattle relies heavily on a single class of drugs, the macrocyclic lactones (MLs). The potency and convenience of the MLs, along with the low cost of generic formulations, have largely supplanted the need for critical thinking about parasite control, and rote treatment has become the default 'strategy'. This approach to parasite control has exerted substantial pressure to select populations of nematodes that can survive recommended dosages of ML products. Although macrocyclic lactones have been available for over 30 years, putative ML resistance in U.S. cattle was not reported until fairly recently. This pattern begs the question, "Is this a new, emergent problem, or an old issue that is finally commanding some attention?" The implications of bovine anthelmintic resistance should stimulate a paradigm shift for U.S. cattle producers and their advisors. However, there are significant obstacles to changes in current thinking. It is anticipated that cattle producers will be extremely reluctant to abandon historical practices unless they can be convinced of the value of alternatives that are communicated through targeted education, practical demonstrations, economic analyses, and scientific evidence. Historically, the management advice of practitioners has not relied strongly on parasite epidemiology, and practitioners may not have the knowledge to implement evidence-based recommendations. Pharmaceutical companies could play a significant role in helping to shape and shift the thinking about sustainable use of anthelmintics. However, their primary responsibility is to stockholders, and they have strong economic incentives for maintaining the status quo. It is complicated and difficult to change attitudes and practices, and it will take more than logic or fear to shift the parasite control paradigm in the U.S. cattle industry. Achieving that goal will require collaboration among stakeholders, a consistent, straightforward and understandable message about resistance, and recommendations that are practical as well as effective. But if we hope to ultimately influence producers and their advisors, we need to be conscious of how individuals and groups change their minds.

Efficacy of domperidone gel in an induced model of fescue toxicosis in periparturient mares.

The objective was to evaluate the efficacy of domperidone in the prevention of reproductive complications of fescue toxicosis in periparturient mares. Pregnant mares at ≤310 days of gestation were fed ≥200 µg ergovaline per kg diet daily in endophyte-infected fescue hay and seed, starting ≥30 days before their expected foaling date (EFD: 340 days after breeding). Thirty-five mares were randomized to a treatment group to receive either domperidone gel (n = 20, 1.1 mg/kg, PO, once daily) or placebo (n = 15). Treatment was initiated 10 to 15 days before the EFD and continued for 5 days after foaling. "Treatment success" was defined as foaling within 14 days of the EFD, adequate mammary development on the day of foaling, and adequate lactation for 5 days postpartum. Twenty-seven mares were included in the effectiveness analysis. More mares in the domperidone group (12/13, P < 0.0001) were treatment successes than in the control group (1/14). Gestation length was shorter (P = 0.0011), and lactation at foaling (P = 0.0011) was better for the domperidone-group mares. Foals from two control mares were born dead and four others died or were euthanized within a few days after birth, compared with one foal death (an autolyzed twin) from a domperidone-treated mare. Plasma IgG concentrations were evaluated in 24 foals. Failure of passive transfer of immunoglobulins (IgG <800 mg/dL) occurred in 13/16 (81%) foals of domperidone-group mares and 7/8 (88%) foals of control mares. In conclusion, the reproductive complications of fescue toxicosis in periparturient mares induced by a fescue seed/hay model were prevented by treatment with domperidone.

Plasma concentrations of endotoxin and platelet activation in the developmental stage of oligofructose-induced laminitis.

The link between the fermentation of carbohydrate in the equine large intestine and the development of acute laminitis is poorly understood. Absorption of endotoxin (lipopolysaccharide; LPS) into the plasma has been observed in one experimental model of laminitis, but does not cause laminitis when administered alone. Thus, the potential role of endotoxin is unclear. Platelet activation has previously been demonstrated in the developmental stage of laminitis. Equine platelets are more sensitive than leukocytes to activation by endotoxin, and can be activated directly by LPS in the low pg/ml range, activating p38 MAP kinase and releasing serotonin (5-HT) and thromboxane. The objectives of this study were firstly to determine whether endotoxin and platelet activation could be measured in the plasma of horses in the developmental phase of laminitis induced with oligofructose. Secondly, the time course of events involving platelet activation and platelet-derived vasoactive mediator production was investigated. Laminitis was induced in six Standardbred horses by the administration of 10 g/kg bwt of oligofructose. Plasma samples were obtained every 4h, and platelet pellets were obtained by centrifugation. LPS was measured using a kinetic limulus amebocyte lysate assay, and platelet activation was assessed by Western blotting for the phosphorylated form of p38 MAP kinase. Plasma 5-HT was assayed by HPLC with electrochemical detection and thromboxane B(2) was measured by radioimmunoassay. Clinical signs of laminitis and histopathologic changes were observed in lamellar sections from five of the six horses. Onset of lameness was between 20 and 30 h after the administration of oligofructose. LPS increased above the limit of detection (0.6 pg/ml) to reach a peak of 2.4+/-1.0 pg/ml at 8 h. TNFalpha was also detectable in the plasma from 12 to 24 h. There was a time-dependent increase in platelet p38 MAPK phosphorylation, which peaked at approximately 12 h (3.8+/-1.3 fold increase); plasma 5-HT and thromboxane increased steadily after this time (2.9+/-0.6 and 11.3+/-5.0 fold increases, respectively). These data indicate that small quantities of endotoxin may move into the circulation from the large intestine after the sharp decrease in pH that occurs as a result of carbohydrate fermentation. Correlating these findings with in vitro studies suggests that LPS may primarily activate platelets, leading indirectly to the activation of leukocytes. Therefore, endotoxin may contribute in the initiation of the early inflammatory changes observed in experimental models of acute laminitis.

A multicenter evaluation of the effectiveness of Quest Gel (2% moxidectin) against parasites infecting equids.

Controlled trials with a common protocol were conducted in Idaho, Illinois and Tennessee to evaluate anthelmintic effectiveness of Quest Gel (QG; 2% moxidectin) against lumenal parasites in horses. Candidate horses were required to have naturally acquired nematode infections, as confirmed by presence of strongylid eggs in feces. At each site, 24 equids were blocked on the basis of pretreatment strongyle fecal egg counts (EPG) and randomly assigned to treatments within blocks. Within each block of two animals, one received QG on Day 0 at a dosage of 0.4 mg moxidectin/kg b.w. and one was an untreated control. Body weights measured the day before treatment served as the basis for calculating treatment doses. Horses assigned to treatment with QG received the prescribed dose administered orally with the commercially packaged Sure Dial syringe. Horses were necropsied 12-14 days after treatment, and lumenal parasites and digesta were harvested separately from each of five organs, including the stomach, small intestine, cecum, ventral colon and dorsal colon. Parasites from stomachs and small intestines were identified to genus, species and stage. Micro- (i.e., < 1.5 cm) and macroparasites (i.e., > 1.5 cm) in aliquots from the cecum, ventral colon and dorsal colon were examined in aliquots of approximately 200 parasites until at least 600 parasites had been identified to genus, species and stage or until all parasites in the 5% aliquot were examined, whichever occurred first. Data were combined across sites and analyzed by mixed model analysis of variance to assess the fixed effect of treatment and random effects of site and block within site. Because QG does not contain a cestocide, efficacy of QG against tapeworms was not significant (P > 0.05). Based on geometric means, however, efficacy of QG was greater than 90% (P < 0.05) against 38 species and developmental stages of cyathostomes, strongyles, bots, larval pinworms and ascarids encountered in at least 6 of 36 control horses in the combined data set. None of the horses treated with moxidectin exhibited evidence of adverse effects. Study results demonstrate QG, administered to horses with naturally acquired endoparasite infections at a dosage of 0.4 mg moxidectin/kg b.w., was highly effective against a broad range of equine parasitic infections.

Evaluation of the efficacy of emodepside+praziquantel topical solution against cestode (Dipylidium caninum, Taenia taeniaeformis, and Echinococcus multilocularis) infections in cats.

Emodepside+praziquantel topical solution was developed to provide broad-spectrum anthelmintic activity against gastrointestinal parasites in cats. Eight controlled studies were conducted to evaluate the efficacy of a topical solution of emodepside (3 mg/kg) and praziquantel (12 mg/kg) (Profender, BayerAG, Leverkusen, Germany) against feline infections with three species of cestodes. Studies featured naturally acquired infections of Dipylidium caninum or Taenia taeniaeformis, or experimental infections with Echinococcus multilocularis that were placebo-controlled, randomized and blinded. Cats were euthanatized and necropsied between 2 and 11 days after treatment, depending on the target parasite. The efficacy of emodepside+praziquantel topical solution was 100% against D. caninum and T. taeniaeformis, and 98.5- 100% against E. multilocularis. No significant systemic or local adverse reactions to treatment were noted in cats that received the combination. Topical treatment of cats with emodepside+praziquantel topical solution was safe and highly effective against cestode infections.

Evaluation of the efficacy of emodepside plus praziquantel topical solution against ascarid infections (Toxocara cati or Toxascaris leonina) in cats.

Eleven controlled studies were conducted in the United States and Europe to evaluate the efficacy of a topical solution of emodepside (3 mg/kg)+praziquantel (12 mg/kg) (Profender, Bayer AG, Leverkusen, Germany) against infection with various stages of the ascarid nematodes Toxocara cati and Toxascaris leonina. Infections were induced by administration of larvated ascarid eggs, and stage-specific efficacy was evaluated by treating cats at scheduled intervals post-inoculation. All studies featured random allocation to treatment groups, placebo-treated control animals and assessment of outcome measures by masked personnel. The product (emodepside+praziquantel topical solution) was 100% effective against mature adults and immature adult T. cati. In addition, it was 96.8% effective against third stage larvae and at least 99.4% effective against fourth stage larvae of T. cati, respectively. Efficacy against mature, immature adult and L4 stages of T. leonina exceeded 93.4%, but regulatory "adequacy of infection" criteria were not met in some studies. No adverse reactions to treatment were noted in cats treated with the emodepside+praziquantel topical solution.

Comparison of endoscopic, necropsy and histology scoring of equine gastric ulcers.

Equine gastric ulcer syndrome (EGUS) represents a major health problem in performance horses. Much debate exists regarding endoscopic gastric ulcer scoring systems and their ability accurately to predict severity or depth of gastric ulcers. The purpose of this study was to evaluate the ability of an endoscopist to count gastric ulcers and predict gastric ulcer severity or depth using 2 endoscopic scoring systems and compare them to the same gastric ulcers see on necropsy and histopathology. Endoscopic examination of the stomach was performed under general anaesthesia on 23 mixed breed yearling horses, after feed was withheld for 24 h. Gastric ulcers were scored using 2 systems, number/severity-scoring (N/S) and practitioner simplified (PS) systems. After endoscopy, the horses were subjected to euthanasia and the stomach mucosa examined blindly and scored again at necropsy using above scoring systems. Representative gastric ulcers were then placed in 10% formalin and processed routinely for histopathology. The gastric ulcers were scored using a histopathology system (HSS) based on ulcer depth. Number scores in the N/S scoring system and PS on endoscopic and necropsy examinations were compared using Friedman 2 way analysis of variance. Where significant differences between variables were found a post hoc analysis was conducted using a Tukey's Studentised range (HSD) test. Severity scores using the N/S (ENGS) and PS scores recorded for the stomach via endoscopy and scores from HSS were evaluated for significant association using a Mantel-Haenszel Chi-square and Pearson moment correlation coefficient analysis. Significance was P < 0.05. All horses had gastric ulcers in the nonglandular mucosa via endoscopic examination and at necropsy examination. Mean nonglandular ulcer number (ENGN) score was significantly (P = 0.0024) lower on endoscopic examination compared to the score at necropsy (NNGN); whereas PS scores were not significantly different on endoscopy when compared to necropsy examination. A significant but weak association was found between ENGS and HSS (3.89, P = 0.048; r = 0.453, P = 0.045) and no correlation was found between PS and HSS (1.2, P = 0.272; r = 0.117; P = 0.622). Only 1/23 horses had glandular ulcers observed via endoscopic examination whereas, 6/23 horses had glandular ulcers at necropsy and on histopathology. The prevalence of EGUS is high in stalled yearling horses. The endoscopist may underestimate the number of gastric ulcers and may not be able accurately to predict the severity or depth of those ulcers present in the nonglandular equine stomach. Furthermore, the endoscopist may miss glandular gastric ulcers.

Dose confirmation studies of moxidectin 1% non-aqueous injectable and moxidectin 0.5% pour-on formulations against experimentally induced infections of larval and adult stage Oesophagostomum radiatum and Trichuris discolor in cattle.

Separate controlled trials were conducted to evaluate the efficacy of two formulations of moxidectin (1% non-aqueous injectable solution and 0.5% pour-on (Cydectin) against larval or adult stages of Oesophagostomum radiatum and Trichuris discolor infecting cattle. Fifty-three strongylate-free dairy breed steer calves were obtained from commercial sources. After a brief acclimation period, calves were randomly divided into two pools to evaluate the efficacy of the moxidectin formulations against targeted larval (n = 27 calves) or adult (n = 26 calves) parasites. Calves in the larvacidal trial were inoculated on Day -16 relative to treatment with approximately 1000 embryonated Trichuris spp. eggs and approximately 640 infective Oesophagostomum spp. larvae. Calves were allocated by lottery to one of three treatment groups (n = 8 per group), which included: Group 1--moxidectin 0.5% pour-on (0.5 mg/kg body weight (BW)) applied topically; Group 2--moxidectin 1% non-aqueous injectable (0.2 mg/kg BW) administered subcutaneously; Group 3--untreated controls. Treatments were administered on Day 0 and calves were housed by group with no contact among animals of different treatments. Three sentinel calves were necropsied on Day 0 of the larvacidal trial to assess viability of larval inocula. On Days 14, 15 and 16 after treatment, calves were euthanatized (two or three from each group per day) and samples of gut contents were collected for determination of total worm counts. On Day -63 relative to treatment, calves in the adulticidal efficacy trial were inoculated with approximately 1000 embryonated Trichuris eggs and then on Day -35 with approximately 2500 infective Oesophagostomum spp. larvae. Fecal samples were collected on Day -7 and the 24 calves with the highest egg counts were assigned by lottery to the following three treatment groups (n = 8 per group): Group 4--moxidectin 0.5% pour-on; Group 5--moxidectin 1% injectable; Group 6--untreated controls. Details of experimental treatments, calf housing and necropsy scheduling were similar to the larvacidal trial. In both the larvacidal and adulticidal trials, inocula contained a variety of parasites in addition to the targeted species. Based on geometric means, both moxidectin 0.5% pour-on and moxidectin 1% non-aqueous injectable significantly reduced (P < 0.05) numbers of Oesophagostomum spp. and Trichuris spp. with anthelmintic efficacies of >99% when used against adult or larval stages of infection. In addition, both formulations of moxidectin demonstrated >95% efficacy (P < 0.05) against larval stages of Strongyloides papillosus. The pour-on formulation had >97% adulticidal and larvacidal efficacy against Cooperia spp. females, while the injectable product was effective against female Cooperia spp. larvae and Cooperia oncophora adult males.

World association for the advancement of veterinary parasitology (WAAVP): second edition of guidelines for evaluating the efficacy of equine anthelmintics.

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp., which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.

Efficacy of moxidectin equine oral gel against endoscopically-confirmed Gasterophilus nasalis and Gasterophilus intestinalis (Diptera: Oestridae) infections in horses.

A 3 m, video gastroscope was used to screen 47 horses suspected of being naturally infected with equine bot larvae. 17 of 47 (36.2%) candidate horses harbored Gasterophilus nasalis larvae in the proximal duodenum and 46 of 47 (97.9%) had G. intestinalis larvae in the stomach. All horses infected with G. nasalis had concurrent infections with G. intestinalis. 14 horses with dual infections were allocated randomly to two treatment groups. Seven horses in Group 1 received 2% moxidectin oral gel once at a dosage of 0.4 mg/kg bodyweight (BW), and seven horses in Group 2 were untreated controls. 14 days after treatment, all horses were necropsied and the stomach and proximal duodenum harvested from each. Bot larvae were recovered, identified to species and instar, and counted. At the label dosage, moxidectin oral gel was 100 and 97.6% effective (P < 0.05) against third-instar G. nasalis and G. intestinalis, respectively. In addition to demonstrating the boticidal efficacy of moxidectin, this trial illustrated that gastroscopy/duodenoscopy is a feasible method for confirming infections with different species of bot larvae in the horse.

Current concerns about control programs in temperate climates.

Efforts to control cyathostome nematodes in temperate climates have not been uniformly successful, as evidenced by contemporary reports of clinical disease and widespread anthelmintic failure. Indeed, effective control is confounded by numerous factors, including ignorance of local transmission patterns, confusing or conflicting control recommendations, and use of ineffective anthelmintics or regimens. Most of these problems are universal rather than being climatically unique, and it is important to recognize that they are mere symptoms of larger and more comprehensive problems. The most basic problem in managing cyathostomes is inadequate knowledge of biological factors that influence control recommendations. These include population dynamics, arrested development, host resistance, and regional bionomics. Another hindrance is the absence of objective criteria to define effective control. Target fecal egg counts are arbitrary and subjective, and parameters to measure the subclinical impact of cyathostome infection in well-managed horses have not been identified. The final general challenge to effective parasite control is motivation and education of equine practitioners and horse owners, who currently receive much of their parasite control information in the form of biased advertising. Ultimately, more effective equine parasite control will result from collaborative efforts of basic research, clinical application, and improved information transfer.

Results of a survey to assess knowledge and expectations of veterinarians and their clients regarding heartworm preventives and vaccinations in dogs.

OBJECTIVE: To determine the knowledge and expectations of veterinarians and clients regarding heartworm preventives and annual vaccinations for dogs. DESIGN: Practitioner and client survey. SAMPLE POPULATION: 435 veterinarians and 1,805 clients. PROCEDURE: A survey was mailed to veterinarians requesting information from them and their dog-owning clients on expectations and knowledge regarding heartworm preventives and annual vaccinations. Responses of veterinarians were compared with those of clients, and both were compared with label indications. RESULTS: Expectations of veterinarians and clients regarding heartworm preventives were similar and usually were consistent with regulatory interpretation of label terms. Of clients purchasing heartworm preventives, 38% did not know that the medication was effective against intestinal nematodes. Veterinarians and clients would be unsatisfied with a product that reduced, but did not eliminate, all intestinal nematodes. Most clients knew that annual vaccinations included distemper virus, parvovirus, and rabies virus, but about half of them did not know that other antigens were in the vaccines. CLINICAL IMPLICATIONS: Effects of heartworm preventives and diseases for which dogs are annually vaccinated should be explained fully to clients.

Comparison of the efficacies of three heartworm preventives against experimentally induced infections with Ancylostoma caninum and Toxocara canis in pups.

Forty 11- to 12-week-old helminth-naive Beagles were categorized by sex and weight and randomly assigned to 4 treatment groups (group 1, ivermectin/pyrantel pamoate; group 2, milbemycin oxime; group 3, untreated control; group 4, diethylcarbamazine/oxibendazole). Each pup was inoculated PO with approximately 100 infective Ancylostoma caninum larvae and 100 larvated Toxocara canis eggs on day 0, and repeatedly at 7-day intervals thereafter until day 56. Administration of anthelmintics also began on day 0, and subsequent treatments were administered according to label recommendations at 30-day intervals (groups 1 and 2) or daily (group 4) for a period of 90 consecutive days. Body weight and A caninum and T canis fecal egg counts were measured at weekly intervals, and clinical observations of health status were conducted twice daily. Pups were euthanatized on day 90, and total gastrointestinal worm burdens were determined. Compared with mean A caninum egg counts of group-3 control pups, egg counts in group-1 pups were significantly (P < or = 0.0001) lower on every sampling days 35, 42, 49, 63, 70, 77, and 84, and were consistently the highest of all treated groups, and egg counts of group-4 pups were significantly (P < or = 0.0001) lower on every sampling date from day 14 to day 90, and were consistently the lowest of all treated groups. Compared with mean A caninum egg counts of group-3 pups, egg counts in group-1 and group-2 pups were lower by 97.8 and 90.8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)