An unblinded randomized study of influenza A/H1N1 2009 (swine flu)resistance under standard and extended duration Oseltamivir treatment

INTERVENTION: Adults or subjects >40 kg will be randomised in a ratio of 1:1 to a standard 75mg twice a day for 5 days or an extended 75mg tiwice a day for 10 days. The mode of adminstration is an oral capsule Children will be randomised in a ratio of 1:1 to a standard dose for 5 days or an extended dose for 10 days powder for oral suspension, which when reconstituted with water to a concentration of 1.2% contains 12 mg/mL oseltamivir. The dose is calculated by weight. 15 kg or less 60 mg per day divided into 2 doses 15–23 kg 90 mg per day divided into 2 doses 24–40 kg 120 mg per day divided into 2 doses CONDITION: influenza A/H1N1 2009 PRIMARY OUTCOME: The difference in the proportion of patients shedding virus with each duration and the proportion which exhibit resistance. Nasopharyngeal swabs will be obtained from both nostrils. The specimens will be analyzed for influenza viruses by polymerase chain reaction (PCR) methods within 48 hrs. SECONDARY OUTCOME: Differences in reduction of viral load, measured at days 5 and 10, in subjects given standard and extended duration oseltamivir. For subjects that are PCR positive, phenotypic viral sensitivity to oseltamivir will be determined by means of the NA Star neuraminidase chemilumiscent assay. In instances where resistance is detected, sequencing of the viral genome will be undertaken to identify the relevant resistance mutations. INCLUSION CRITERIA: 1. Male and non‐pregnant female subjects age greater than or equal to 5 years: 2. A positive Influenza A Rapid Antigen Test (RAT) performed on an adequate nasopharyngeal specimen, in accordance with the manufacturer’s instructions. If the RAT is negative but, in the investigator’s opinion, there is strong clinical suspicion of any type of influenza then the subject may be enrolled. 3. Presence of fever at the time of screening of greater or equal to 37.8 degrees celius (greater or equal to 100.04 degrees F) taken orally. A subject self‐report of a history of a fever or feverishness within the 24 hours prior to screening will also qualify for enrolment in the absence of documented fever at the time of screening. 4. Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms). 5. Onset of symptoms no more than 48 hours before presentation for screening. 6. Female of non‐childbearing potential, either surgically ster