Pulmonary fibrosis and gammaherpesvirus infection in horses

Pulmonary fibrosis is a devastating and often progressive condition leading to exercise intolerance and frequently the demise of the animal. Although uncommonly encountered in horses, the condition is intensely researched both in human medicine and animal models. Viral infections have long been suspected to play a part in the development of pulmonary fibrosis and neoplastic conditions in other species. In 2007, an association between equine herpesvirus 5 (EHV‐5) infection and nodular pulmonary fibrosis in horses was suggested and the name equine multinodular pulmonary fibrosis (EMPF) was introduced. Recently, the presence of EHV‐5 in equine lymphoma has also emerged. The case report by Schwarz et al. in this issue describes a horse suffering from concurrent T cell leukaemia and EMPF in association with EHV‐5. This article summarises current knowledge about EMPF and EHV‐5 infections in horses, recent developments in the understanding of pulmonary fibrosis in man and the proposed contribution of viral infections to pulmonary fibrosis and neoplastic conditions.     

Influenza A viruses with truncated NS1 as modified live virus vaccines: Pilot studies of safety and efficacy in horses

Reasons for performing study: Three previously described NS1 mutant equine influenza viruses encoding carboxyterminally truncated NS1 proteins are impaired in their ability to inhibit type I IFN production in vitro and are replication attenuated, and thus are candidates for use as a modified live influenza virus vaccine in the horse. Hypothesis: One or more of these mutant viruses is safe when administered to horses, and recipient horses when challenged with wild‐type influenza have reduced physiological and virological correlates of disease. Methods: Vaccination and challenge studies were done in horses, with measurement of pyrexia, clinical signs, virus shedding and systemic proinflammatory cytokines. Results: Aerosol or intranasal inoculation of horses with the viruses produced no adverse effects. Seronegative horses inoculated with the NS1‐73 and NS1‐126 viruses, but not the NS1‐99 virus, shed detectable virus and generated significant levels of antibodies. Following challenge with wild‐type influenza, horses vaccinated with NS1‐126 virus did not develop fever (>38.5°C), had significantly fewer clinical signs of illness and significantly reduced quantities of virus excreted for a shorter duration post challenge compared to unvaccinated controls. Mean levels of proinflammatory cytokines IL‐1β and IL‐6 were significantly higher in control animals, and were positively correlated with peak viral shedding and pyrexia on Day +2 post challenge. Conclusion and clinical relevance: These data suggest that the recombinant NS1 viruses are safe and effective as modified live virus vaccines against equine influenza. This type of reverse genetics‐based vaccine can be easily updated by exchanging viral surface antigens to combat the problem of antigenic drift in influenza viruses.     

Report of the Second Havemeyer EHV‐1 Workshop,Steamboat Springs,Colorado, USA,September 2008

This report summarises the findings of the Second Havemeyer EHV‐1 Workshop, which was held in Steamboat Springs, Colorado, USA in September 2008. A total of 38 delegates, consisting of veterinary clinicians and scientists from academia and industry participated in a series of sessions that focused on equine herpesvirus myeloencephalopathy (EHM). Each session consisted of a review, followed by short presentations on current research topics. The sessions included EHM epidemiology, in vivo and in vitro models for studying EHM, EHV‐1 virulence determinants, real‐time PCR diagnostics, antiviral medications and new vaccination technologies. The report summarises the key advances identified during and since the meeting. Citations are restricted to selected reviews and papers published since the workshop.     

Post‐anesthetic pulmonary edema in two horses

Case 1 A two‐year old, 462 kg Standard bred horse was anesthetized for arthroscopy and castration. During anesthesia, hyperemia of the mucosal membranes and urticaria were noticed. During 5 hours of anesthesia subcutaneous edema of the eyelids and neck region developed. In the recovery box, the orotracheal (OT) tube was left in situ and secured in place with tape. Following initial attempts to stand, the horse became highly agitated and signs consistent with pulmonary edema developed subsequently. Arterial hypoxemia (PaO₂: 3.7 kPa [28 mmHg]) and hypocapnia (PaCO₂: 3.1 kPa [23 mmHg]) were confirmed. Oxygen and furosemide were administered. The horse was assisted to standing with a sling. Therapy continued with bilateral intra‐nasal oxygen insufflation. Ancillary medical therapy included flunixin meglumine, penicillin, gentamycin and dimethylsulfoxide. Following 7 hours of treatment the arterial oxygen tensions began to increase towards normal values. Case 2 An 11‐year old, 528 kg Paint horse was anesthetized for surgery of a submandibular mass. The 4‐hour anesthetic period was unremarkable. The OT tube was left in situ for the recovery. During recovery, the horse was slightly agitated and stood after three attempts. Clinical signs consistent with pulmonary edema and arterial hypoxemia (PaO₂: 5 kPa [37.5 mmHg]) subsequently developed following extubation. Respiratory signs resolved with medical therapy, including unilateral nasal oxygen insufflation, furosemide, flunixin meglumine and dimethylsulfoxide. The diagnosis of pulmonary edema in these horses was made by clinical signs and arterial blood‐gas analysis. While pulmonary radiographs were not taken to confirm the diagnosis, the clinical signs following anesthesia support the diagnosis in both cases. The etiology of pulmonary edema was most likely multifactorial.     

A survey of respiratory viruses in New Zealand horses

AIMS: To determine which viruses circulate among selected populations of New Zealand horses and whether or not viral infections were associated with development of respiratory disease.

METHODS: Nasal swabs were collected from 33 healthy horses and 52 horses with respiratory disease and tested by virus isolation and/or PCR for the presence of equine herpesviruses (EHV) and equine rhinitis viruses.

RESULTS: Herpesviruses were the only viruses detected in nasal swab samples. When both the results of nasal swab PCR and virus isolation were considered together, a total of 41/52 (79%) horses with respiratory disease and 2/32 (6%) healthy horses were positive for at least one virus. As such, rates of virus detection were significantly higher (p<0.001) in samples from horses with respiratory disease than from healthy horses. More than half of the virus-positive horses were infected with multiple viruses. Infection with EHV-5 was most common (28 horses), followed by EHV-2 (27 horses), EHV-4 (21 horses) and EHV-1 (3 horses).

CONCLUSIONS: Herpesviruses were more commonly detected in nasal swabs from horses with respiratory disease than from healthy horses suggesting their aetiological involvement in the development of clinical signs among sampled horses. Further investigation to elucidate the exact relationships between these viruses and respiratory disease in horses is warranted.

CLINICAL RELEVANCE: Equine respiratory disease has been recognised as an important cause of wastage for the equine industry worldwide. It is likely multifactorial, involving complex interactions between different microorganisms, the environment and the host. Ability to control, or minimise, the adverse effects of equine respiratory disease is critically dependent on our understanding of microbial agents involved in these interactions. The results of the present study update our knowledge on the equine respiratory viruses currently circulating among selected populations of horses in New Zealand.     

An equine herpesvirus 1 (EHV1) abortion storm at a riding school

Summary

An outbreak of EHV1 abortions occurred at a riding school in the Netherlands in 1991. Seven of twelve pregnant mares aborted, and another foal died at 8 days of age. Six abortions occurred within 12 days in March after an initial abortion on 8 February. Four mares delivered live foals. Virological examination of four aborted foals revealed an EHV1 infection. Serological results for paired sera from 17 horses suggested, that the initial abortion on 8 February was the index case, and probably caused the other six abortions. The index case could well have been caused by reactivation of latent virus induced by transport stress. The laboratory results are discussed in the light of the present knowledge of the pathogenesis and epidemiology of EHV1 abortion.     

African horse sickness in naturally infected,immunised horses

To determine whether subclinical cases, together with clinical cases, of African horse sickness (AHS) occur in immunised horses in field conditions, whole blood samples were collected and rectal temperatures recorded weekly from 50 Nooitgedacht ponies resident in open camps at the Faculty of Veterinary Science, University of Pretoria, Onderstepoort, during 2008–2010. The samples were tested for the presence of African horse sickness virus (AHSV) RNA by a recently developed real‐time RT‐PCR. It was shown that 16% of immunised horses in an AHS endemic area were infected with AHSV over a 2 year period, with half of these (8%) being subclinically infected. The potential impact of such cases on the epidemiology of AHS warrants further investigation.     

Molecular Investigation of the Viral Kinetics of Equine Herpesvirus‐1 in Blood and Nasal Secretions of Horses after Corticosteroid‐Induced Recrudescence of Latent Infection

Background: Recrudescence of latent equine herpesvirus 1 (EHV‐1) with subsequent viral shedding via nasal secretions is a potential source of infection for susceptible horses and has been implicated in outbreaks occurring in closed populations. Objectives: To describe the viral kinetics of reactivated EHV‐1 in blood and nasal secretions from latently infected horses after administration of corticosteroids, and to study the infectious nature of reactivated EHV‐1 to sentinel horses. Animals: Eight healthy horses. Methods: Four horses infected 4 months previously with EHV‐1 received dexamethasone on 5 consecutive days. Four seronegative horses served as sentinels and had direct contact with the latently infected horses. All horses were monitored daily for development of clinical signs. Whole blood and nasal secretions were collected daily for molecular detection and cell culture of EHV‐1. Serum was collected weekly for the detection of antibodies against EHV‐1. Results: All horses in the latently infected group showed transient molecular detection of EHV‐1 in blood and nasal secretions, but only 1 horse developed fever. Three latently infected horses developed an increase in antibody concentrations against EHV‐l. Viral cultures remained negative for all latently infected horses after corticosteroid administration. None of the sentinel horses developed clinical signs, viremia, viral shedding, or seroconversion. Conclusions and Clinical Importance: EHV‐1 was successfully reactivated after corticosteroid administration in latently infected horses. However, transmission of reactivated virus to sentinel horses was unsuccessful. Failure to effectively transmit EHV‐1 to susceptible horses may have resulted from the low level and short period of viral shedding in latently infected horses.     

The efficacy of a commercial ELISA as an alternative to virus neutralisation test for the detection of antibodies to EAV

Infection with equine arteritis virus is a notifiable disease with sporadic occurrence in the UK. As stallions may harbour the virus after infection, horses are screened for exposure by serological testing prior to breeding. The virus neutralisation test is considered the 'gold standard' serological screening test, but it is time-consuming and labour intensive; consequently there is a move towards more rapid screening methodology. In this study, a commercially available EVA antibody ELISA is assessed. The ELISA performed poorly with a specificity [corrected] of 26% and a sensitivity [corrected] of 96% in the samples analysed. It was concluded that this ELISA would be of little value for reducing sample turnaround time. The study emphasises the need for in-house validation of commercially available kits.     

Intra‐abdominal hypertension in horses

Intra‐abdominal hypertension (IAH) may lead to a multiple organ dysfunction syndrome associated with significant dysfunction of the cardiovascular, respiratory, renal, gastrointestinal and central nervous systems of human patients. A recent prospective multicentre epidemiological investigation in man concluded that IAH was associated with an increased risk of mortality in critically ill patients. In this review, we present current information pertaining to the potential clinical importance of IAH in the context of equine clinical practice. In conclusion, consideration of intra‐abdominal pressure should be a part of the clinical assessment of patient well‐being in critically ill equine patients.     

Subepiglottic cysts in 15 horses

Subepiglottic cysts (SECs) are an infrequent cause of upper respiratory tract noise and exercise intolerance in horses. They may also be associated with no clinical signs and be an incidental finding during routine upper airway endoscopy. The aim of this study was to assess the effect on performance of horses undergoing surgical removal of SECs. The case records of 15 horses (1995–2009) diagnosed with SECs were retrieved. Eleven (73%) of the 15 horses included in the study were Thoroughbred racehorses. Eleven (73%) of the 15 horses had no preoperative clinical signs related to the SECs, with the remaining 4 (27%) having a respiratory noise (n = 4), nasal discharge (n = 1), difficulty swallowing (n = 1) or a cough (n = 1). Endoscopic examination in the standing horse was diagnostic in 93% (n = 14) of horses. Nine (82%) of the 11 Thoroughbred horses were yearlings, of which only one horse (11%) presented with clinical signs consisting of a respiratory noise and nasal discharge. Four of the 11 (36%) Thoroughbred horses were found to have concurrent epiglottic entrapment. Surgical removal was successful in all cases. Eight of the 11 (73%) Thoroughbred horses in this study raced following SEC removal. The majority of SECs are identified during routine endoscopic examinations and are not associated with clinical signs. The prognosis following surgical removal of SECs is good and future performance does not appear to be affected.     

A comparative study of xylazine-induced mechanical hypoalgesia in donkeys and horses

ObjectiveTo compare the effects of xylazine on mechanical nociceptive thresholds in donkeys and horses.Study designRandomized, controlled, crossover, Latin-square, operator-blinded design.AnimalsSix 3.1 ± 0.89 year old standard donkeys weighing 145.0 ± 30.5 kg and six 9.6 ± 4.4 year old Thoroughbred horses weighing 456.0 ± 69.0 kg.MethodsEach animal received one of four doses of xylazine (0.5, 0.7, 0.9, and 1.1 mg kg^?1), or acepromazine (0.05 mg kg^?1) or saline solution (0.9%) intravenously and mechanical nociceptive thresholds were assessed over 90 minutes. The areas under the threshold change versus time curve values for 60 minutes (AUC_0-60) post-drug administration were used to compare the effect of treatment. A 1-week interval was allowed between successive trials on each animal.ResultsAll doses of xylazine, but not acepromazine or saline, increased mechanical thresholds for up to 60 minutes. Xylazine-induced hypoalgesia was dose-dependent and corresponding AUC_0-60 values for each treatment were not significantly different between donkeys and horses (p≥ 0.0697).ConclusionThe hypoalgesic effects of xylazine at four different doses were not different between donkeys and horses.Clinical relevanceXylazine induced a similar degree of mechanical hypoalgesia in donkeys and horses suggesting that similar doses are needed for both species with regard to analgesia.