Development and evaluation of aerosol delivery of antivirals for the treatment of equine virus - induced respiratory infections

Abstract

An aerosol delivery system incorporating the DeVilbiss ultrasonic nebulizer was developed for antiviral chemotherapy of equine viral respiratory infections. The system's delivery capabilities were proven effective by two modes of analysis: (a) a non-destructive, non-invasive radioactive tracer method utilizing a saline solution of DTPA labelled 99mTc and, (b) an invasive-terminal study using fluorescent polystyrene monodispersed latex particles. Particles were efficiently distributed throughout the lung parenchyma with deposition more heavily concentrated in the tracheobronchial region. Amantadine HCl was administered to the lungs of a yearling horse and three yearling Shetland ponies over a single 15-30 minute period with no untoward side effects. Likewise, ribavirin was aerosolized into the respiratory trace of an adult pony and a yearling horse for 15-30 minutes twice a day for three and seven days respectively. Neither the horse nor pony demonstrated signs of clinical illness or other signs of ribavirin toxicity. Attempts to produce a reproducible equine influenza disease model were made. Sixteen young horses (1-2 years old) and Miniature Horse foals (5 to 8 weeks old) were inoculated with equine influenzaviruses A/1 and A/2 either singly, in combination, or mixed with other equine viruses associated with respiratory disease (equine herpesvirus I, equine rhinoviruses I & II). Various combinations and concentrations of virus(es) were administered by different routes of delivery including intranasal instillation with polystyrene catheters, via a jet-injector, and by ultrasonic and air-jet nebulization. As determined by virus isolation and/or serological responses, 44% of the animals became infected. One foal of sixteen equids showed a 24 hour clinical response. During these studies we were unsuccessful in developing a consistent respiratory disease model. Without this model the efficacy of antiviral compounds can not be assessed. From the data generated in these studies, the implication of equine influenzaviruses as the major single etiological agents responsible for equine respiratory disease is brought into question. Further, we propose that equine respiratory disease is a multiple agent-induced disease, which needs extensive investigation.