Nasal wash cell counts in the presence or absence of oseltamivir treatment.

<p>A, prophylactic oseltamivir regimen from 2; B, therapeutic oseltamivir regimen from 6 hr post-infection. • (red) high dose (10⁶ pfu); ▴ (blue) low dose (10² pfu); ★ mock infected animals; open symbols represent oseltamivir-treated animals. Means from 5 ferrets (A) or 3–9 ferrets per group (B).</p

Viral RNA loads in ferret respiratory tract tissues.

<p>Ferrets were infected intra-nasally with 10⁶ or 10² pfu Cal/04 and, where indicated, treated with oseltamivir from 6 hr post-infection. Circles show RNA loads for individual animals. Horizontal lines show group means. Filled circles, no treatment; open circles, oseltamivir treated. A, nasal turbinate; B, trachea; C, lung. High, 10⁶ pfu inoculum; Low, 10² pfu inoculum. Samples were taken from 2 ferrets on days 1 to 4, and 3 ferrets on day 5. The sensitivity of the assay was approximately 10³ copies/mg.</p

Summary of severity of pathological changes in untreated or oseltamivir treated ferret tissues.

<p>A. Nasal cavity, B. lung. In each case, changes were scored as minimal (min), mild, moderate (mod), or marked, and were summed for each group of ferrets on each day post-infection. Group size was 2 ferrets, except day 5 which was groups of 3 ferrets. The day 5 summed frequencies have been normalised to facilitate comparison to the other days.</p

Effect of virus dose on parameters of infection with influenza A/California/04/09.

1<p>Mean clinical score is calculated as described in Materials and Methods, and expressed as mean score per ferret per day ± standard error of the mean.</p>2<p>Day of onset refers to median onset of respiratory signs and inactivity from four studies.</p><p>ND, not done.</p

Effect of decreasing infectious dose on virus shedding.

<p>Ferrets were infected intra-nasally, and nasal washes were collected at the intervals shown for virus plaque assay. Markers show geometric mean nasal wash titre from groups of 5 or 8 ferrets; error bars show standard deviation. For days 10 and 14 post-infection, 2 ferrets per group were used. • (red) high dose (10⁶ pfu), ▪ (green) medium dose (104 pfu), ▴ (blue) low dose (102 pfu) inoculum. The lower limit of detection was 10 pfu/ml.</p

Microscopic changes in ferret nasal cavity and lung, with and without oseltamivir treatment.

<p>A. Nasal cavity, low dose, untreated group, 4 dpi. Propria mucosa is infiltrated by marked numbers of mixed inflammatory cells. Overlying respiratory epithelium comprises attenuated, pre-ciliated, regenerating cells (arrow). B. Nasal cavity, low dose with oseltamivir-treated group, 4 dpi. A mild, mononuclear cell infiltrate within the nasal propria mucosa underlying a normal, pseudostratified, columnar, ciliated epithelium (arrow). C. Lung, low dose, untreated group, 5 dpi. Multifocally extensive, mononuclear cell infiltration of parenchyma. Inset: focal, bronchial gland necrosis (asterisk). D. Lung, high dose, untreated group, 5 dpi. Marked infiltration of parenchyma with inflammatory cells by peribronchial and perivascular oedema (Oe) and bronchial gland necrosis (arrow). E. Lung, low dose, oseltamivir-treated group, 5 dpi. Minimal, parenchymal, mononuclear cell infiltrate (arrow). F. Lung, high dose, oseltamivir-treated group, 5 dpi. Mild, peribronchiolar, mononuclear cell infiltration (arrow). Haematoxylin and eosin.</p

Nasal wash virus titres in the presence or absence of treatment with oseltamivir.

<p>A, prophylactic oseltamivir regimen from 2; B, therapeutic oseltamivir regimen from 6 hr post-infection. • (red) high dose (10⁶ pfu); ▴ (blue) low dose (10² pfu); open symbols represent oseltamivir-treated animals. Means from 5 ferrets (A) or 3–9 ferrets per group (B).</p