Ofile associated with HPAI, swine influenza, and seasonal influenza infection. A statistical analysis utilizing only untreated, influenza virus-infected ferrets, was performed to determine correlates of protection by comparing various clinical parameters. Clinical parameters evaluated include survival/mortality, body temperatures, activity, body weights, clinical chemistry parameters, hematology parameters, and viral secretion. Ferrets were infected with 16106 TCID50 of HPAI H5N1 (A/Vn/1203/04), seasonal influenza H3N2 or H1N1 (A/ Brisbane/10/07 or A/New Caledonia/20/1999, respectively), or swine influenza (A/California/04/09) by nasal instillation and observed for 14 days. The challenge titer was chosen based on previous natural history studies performed with each of the 23977191 viruses in the ferret model. On the day of infection, ferrets were anesthetized with TelazolH (16?2 mg/kg, intramuscular) and the infection material was instilled slowly into the nares of the ferrets. Infection with the influenza viruses led to various clinical parameters that could be associated with these viruses. Infection with H5N1 A/Vn/1203/04 resulted in measureable KS 176 biological activity disease and 93 mortality by day 10 post-challenge (Fig. 1). Any ferret surviving through 10 days post-infection fully recovered from the disease. In contrast, seasonal influenza and swine influenza challenge in ferrets did not result in lethality, but did result in a measureable disease state.Weight, Body Temperatures, and Activity Changes Associated with Influenza Virus InfectionInfluenza virus infection in ferrets, regardless of the strain, resulted in a disruption of their normal diurnal temperature fluctuations and an increase in temperature that could be observedwithin 24 hours post-challenge (Fig. 2A). Statistical analyses performed on the absolute temperatures and temperature changes from baseline (Fig. 2A and 2B) suggest that HPAI-infected ferrets experienced significant variations in body temperatures and the fever intensity on various days post-infection when compared to ferrets infected with seasonal- or swine influenza viruses. For instance, animals infected with HPAI exhibited more severe fever, as demonstrated by comparing changes to baseline values. Additionally, infection with HPAI resulted in a longer duration of fever when compared to seasonal and swine influenza-infected animals. Surviving animals infected with influenza virus, regardless of strain, exhibited normal diurnal temperature patterns approximately 9 to 10 days post-challenge. These animals remained relatively normal throughout the remainder of the studies. Itacitinib weight loss is a clinical profile associated with HPAI infection in ferrets. 
Ferrets infected with HPAI lost a significant amount of weight starting two days post-infection (Fig. 2C and 2D). Statistical analysis demonstrates a significant difference in the amount of weight that was lost in animals infected with HPAI when compared to those infected with seasonal or swine influenza. In surviving animals infected with HPAI, the weight appeared to stabilize nine days post-challenge. In contrast, ferrets challenged with seasonal and swine influenza did not experience significant weight loss; moreover, in most cases, the 
weight remained constant or weight gain was observed following infected. Overall, most of the weight loss was associated with HPAI-infected ferrets, which is likely attributed to general malaise and inappetance. Malaise and inappetance is more pronounced in.Ofile associated with HPAI, swine influenza, and seasonal influenza infection. A statistical analysis utilizing only untreated, influenza virus-infected ferrets, was performed to determine correlates of protection by comparing various clinical parameters. Clinical parameters evaluated include survival/mortality, body temperatures, activity, body weights, clinical chemistry parameters, hematology parameters, and viral secretion. Ferrets were infected with 16106 TCID50 of HPAI H5N1 (A/Vn/1203/04), seasonal influenza H3N2 or H1N1 (A/ Brisbane/10/07 or A/New Caledonia/20/1999, respectively), or swine influenza (A/California/04/09) by nasal instillation and observed for 14 days. The challenge titer was chosen based on previous natural history studies performed with each of the 23977191 viruses in the ferret model. On the day of infection, ferrets were anesthetized with TelazolH (16?2 mg/kg, intramuscular) and the infection material was instilled slowly into the nares of the ferrets. Infection with the influenza viruses led to various clinical parameters that could be associated with these viruses. Infection with H5N1 A/Vn/1203/04 resulted in measureable disease and 93 mortality by day 10 post-challenge (Fig. 1). Any ferret surviving through 10 days post-infection fully recovered from the disease. In contrast, seasonal influenza and swine influenza challenge in ferrets did not result in lethality, but did result in a measureable disease state.Weight, Body Temperatures, and Activity Changes Associated with Influenza Virus InfectionInfluenza virus infection in ferrets, regardless of the strain, resulted in a disruption of their normal diurnal temperature fluctuations and an increase in temperature that could be observedwithin 24 hours post-challenge (Fig. 2A). Statistical analyses performed on the absolute temperatures and temperature changes from baseline (Fig. 2A and 2B) suggest that HPAI-infected ferrets experienced significant variations in body temperatures and the fever intensity on various days post-infection when compared to ferrets infected with seasonal- or swine influenza viruses. For instance, animals infected with HPAI exhibited more severe fever, as demonstrated by comparing changes to baseline values. Additionally, infection with HPAI resulted in a longer duration of fever when compared to seasonal and swine influenza-infected animals. Surviving animals infected with influenza virus, regardless of strain, exhibited normal diurnal temperature patterns approximately 9 to 10 days post-challenge. These animals remained relatively normal throughout the remainder of the studies. Weight loss is a clinical profile associated with HPAI infection in ferrets. Ferrets infected with HPAI lost a significant amount of weight starting two days post-infection (Fig. 2C and 2D). Statistical analysis demonstrates a significant difference in the amount of weight that was lost in animals infected with HPAI when compared to those infected with seasonal or swine influenza. In surviving animals infected with HPAI, the weight appeared to stabilize nine days post-challenge. In contrast, ferrets challenged with seasonal and swine influenza did not experience significant weight loss; moreover, in most cases, the weight remained constant or weight gain was observed following infected. Overall, most of the weight loss was associated with HPAI-infected ferrets, which is likely attributed to general malaise and inappetance. Malaise and inappetance is more pronounced in.
