Influenza A virus continues to cause annual epidemics. The emergence of avian viruses in the human population poses a pandemic threat, and has highlighted the need for more effective influenza vaccines and antivirals. Development of such therapeutics would be enhanced by the use of a small-animal model that is permissive for replication of human influenza virus, and for which reagents are available to dissect the host response. A model is presented of nasal and pulmonary infection in adult inbred cotton rats (Sigmodon hispidus) that does not require viral 'adaptation'. It was previously demonstrated that animals infected intranasally with 10 7 TCID 50 of a recent H3N2 influenza, A/Wuhan/359/95, have increased breathing rates. In this report it is shown that this is accompanied by weight loss and decreased temperature. Virus replication peaked within 24 h in the lung, with peak titres proportional to the infecting dose, clearing by day 3. Replication was more permissive in nasal tissues, and persisted for 6 days. Pulmonary pathology included early bronchiolar epithelial cell damage, followed by extensive alveolar and interstitial pneumonia, which persisted for nearly 3 weeks. Interleukin 1 alpha (IL1a), alpha interferon (IFN-a), IL6, tumour necrosis factor alpha (TNF-a), GROa and MIP-1b mRNA were elevated soon after infection, and expression coincided with virus replication. A biphasic response was observed for RANTES, IFN-c, IL4, IL10 and IL12-p40, with increased mRNA levels early during virus replication followed by a later increase that coincided with pulmonary inflammation. These results indicate that cotton rats will be useful for further studies of influenza pathogenesis and immunity.
Since the implementation of the CDC guidelines for maternal intrapartum antibiotic prophylaxis, culture-proved sepsis has become rare at our institution. Although BC did not aid in the diagnosis of sepsis among asymptomatic at risk newborns, close observation in the first 24 h remained critically important.
Forty-one previously healthy children <2 years of age who required mechanical ventilation for respiratory syncytial virus (RSV) infection were randomized to receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0, 1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling demonstrated a significantly greater decline in mean tracheal RSV quantity in the placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21 log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No differences were found between groups in nasal RSV quantity, white blood cell counts in tracheal or nasal aspirates, serum neutralizing antibody titers during convalescence, or duration of mechanical ventilation, intensive care unit stay, or hospital stay.
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