Infection with equid herpesvirus type 1 (EHV-1) leads to respiratory disease, abortion, and neurologic disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism resulting in an amino acid variation of the EHV-1 DNA polymerase (N752/D752) is significantly associated with the neuropathogenic potential of naturally occurring strains. To test the hypothesis that this single amino acid exchange by itself influences neuropathogenicity, we generated recombinant viruses with differing polymerase sequences. Here we show that the N752 mutant virus caused no neurologic signs in the natural host, while the D752 virus was able to cause inflammation of the central nervous system and ataxia. Neurologic disease induced by the D752 virus was concomitant with significantly increased levels of viremia (p = 0.01), but the magnitude of virus shedding from the nasal mucosa was similar between the N752 and D752 viruses. Both viruses replicated with similar kinetics in fibroblasts and epithelial cells, but exhibited differences in leukocyte tropism. Last, we observed a significant increase (p < 0.001) in sensitivity of the N752 mutant to aphidicolin, a drug targeting the viral polymerase. Our results demonstrate that a single amino acid variation in a herpesvirus enzyme can influence neuropathogenic potential without having a major effect on virus shedding from infected animals, which is important for horizontal spread in a population. This observation is very interesting from an evolutionary standpoint and is consistent with data indicating that the N752 DNA pol genotype is predominant in the EHV-1 population, suggesting that decreased viral pathogenicity in the natural host might not be at the expense of less efficient inter-individual transmission.

Summary Plasma ACTH levels have been variable in horses with a positive clinical response for therapy for equine Cushing's Disease (ECD). Therefore, our purpose was to determine the value of monitoring plasma adrenocorticotropin (ACTH) levels during treatment of equine Cushing's disease (ECD) with either cyproheptadine (n = 32) or pergolide (n = 10). First, we validated the chemiluminescent ACTH assay (specificity, precision, accuracy, intra‐assay and interassay variations) and tested methods of handling the whole blood from the time of collection to when the ACTH was assayed. The sensitivity and specificity of high plasma ACTH levels for detecting ECD was determined in a retrospective study on hospitalised horses (n = 68). Surveys were sent to veterinarians who submitted equine ACTH levels that were high initially and had at least 2 ACTH samples to determine the value of monitoring ACTH levels during therapy of ECD. The ACTH chemiluminescent assay was valid. The ACTH was stable when whole blood was collected and held in plastic tubes for 8h before separating the plasma. The sensitivity and specificity of plasma ACTH levels for detecting ECD were 84% (n = 19, 95% CI 60, 97) and 78% (n = 49, 95% CI 63, 88), respectively. Treated horses generally showed a decrease in plasma ACTH. Plasma ACTH levels may be helpful when monitoring therapy of ECD, although improvement in clinical signs should be considered most important. There were no differences between cyproheptadine and pergolide in terms of improvements in any of the clinical signs.

Summary Reasons for performing study: Previous reports of clostridial myonecrosis have either focused on individual case reports or have been small retrospective studies reporting very high mortality rates. Objectives: The objective of this study was to describe the outcome of cases of clostridial myonecrosis submitted to 2 referral equine hospitals in the United States over a 15 year period. Methods: A retrospective study of case material selected on the basis of positive Clostridium spp. culture or the identification of Clostridium spp. by specific fluorescent antibody testing from soft tissue wounds was performed at Cornell and Wisconsin. Results: 37 cases of clostridial myonecrosis were documented. Twenty‐seven horses survived, 8 were subjected to euthanasia and 2 died during treatment for an overall survival rate of 73%. Twenty‐five cases (68%) were associated with Clostridium perfringens alone, 6 cases (16%) with Cl. septicum alone, 4 cases with mixed clostridial infections (11%), 1 case with Cl. sporogenes and 1 with an unspeciated Clostridium spp. The highest survival rate of 81% was docum ented for those cases from which Cl. perfringens alone was isolated. The most common antecedent condition prior to referral was colic. The myonecrotic lesion occurred within 6–72 h of a soft tissue injection in 34 cases but was associated with a wound or laceration in the remaining 3 cases. Of the 34 cases associated with recent injections, 24 were associated with i.m. injections in the cervical region, 4 in the semimembranosus/semitendinosus region, 3 in the gluteal region, 2 with perivascular leakage of drugs administered into the jugular vein and 1 case developed simultaneously in the gluteal and neck region following injections at both sites. Conclusions: Clostridial myonecrosis can occur following the i.m. or inadvertent perivascular administration of a wide variety of commonly administered drugs. It is most common in the neck musculature. Aggressive treatment can be associated with survival rates of up to 81% for cases due to Cl. perfringens alone. Survival rates for other Clostridial spp. tend to be lower. Potential relevance: A combination of high dose i.v. antibiotic therapy and surgical fenestration/debridement is the best approach to cases of clostridial myonecrosis. With rapid diagnosis and therapeutic intervention, horses may have up to an 81% chance of survival.