Therapy of Aujeszky's disease (pseudorabies) in naturally infected and artificially inoculated piglets using BW B759U (9-[1,3-dihydroxy-2-propoxymethyl] guanine).
Two experimental porcine models of Aujeszky's disease (AD) were compared for assessing the efficacy of potential antiviral compounds. While signs were the same following intranasal inoculation and in-contact transmission of the causal herpesvirus, SHV-1 (Suid herpesvirus), the time-course of the disease was different. There was less variation in clinical signs between pigs following artificial infection, but the disease was more severe, making this a consistent but also more stringent test system. A nucleoside analogue, BW B759U (9-[1,3-dihydroxy-2-propoxy-methyl] guanine), was administered intramuscularly in divided twice daily doses at 50 mg kg-1 to three-week-old piglets in these two SHV-1 disease models. In artificially infected animals, in which treatment was begun 1.5 hours preinfection and continued for six days, there was a delay in the onset of clinical signs (4.8 compared with 3.2 days), a 1 log10 reduction in virus shedding, and a 1 to 2 log10 reduction in virus recovered from tissues, but all the treated piglets died from AD. In contrast, none of the BW B759U-treated piglets in the in-contact model system died during the eight-day medication period, although two piglets died subsequently. Mean serum concentrations of BW B759U two hours after intramuscular dosing were about 45 microM, at nine hours 15 to 20 microM and at 17 hours 3.5 microM. The in vitro IC50 of BW B759U against SHV-1 varies from 1.5 to 80 microM depending on the cell line in which the assay is carried out. There were no overt signs of BW B759U toxicity in the treated piglets.