This study will assist in the early detection of influenza resistant to antivirals and will monitor the clinical outcome of adults and children infected with influenza according to subtype and susceptibility. Participants clinically diagnosed with influenza will undergo a rapid diagnostic test and viral sampling at Baseline and on Days 3, 6, and 10. Participants will be clinically managed according to local guidelines and the decision to treat/not treat will be at the discretion of the Investigator.
Study Type
OBSERVATIONAL
Enrollment
4,561
Participants may receive treatment at the discretion of the investigator according to local practice standards, and there is no protocol-specified intervention. However, analyses will be presented separately for participants treated with oseltamivir during the course of the study.
Unnamed facility
Chicago, Illinois, United States
Unnamed facility
Westmead, New South Wales, Australia
Unnamed facility
Bron, France
Unnamed facility
Berlin, Germany
Number of Participants With Genotypic Resistance
Samples were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR). Pre-defined mutations in viral ribonucleic acid (RNA) were noted, the presence of which was defined as genotypic resistance. The number of participants with genotypic resistance at Baseline was reported. The number of participants with genotypic resistance post-Baseline was determined by a collective count of all participants who had a resistance mutation at least once on Days 3, 6, and/or 10. (Hereafter, "H" stands for hemagglutinin and "N" stands for neuraminidase in abbreviations of viral subtype such as H1N1, H1N1pdm09, and H3N2.)
Time frame: Baseline (Day 1) and post-Baseline (Days 3, 6, 10)
Percentage of Participants Exhibiting Treatment-Emergent Resistance by Study Year Among Participants With H3N2 or H1N1pdm09 Infections
Pre-defined mutations in viral RNA were noted, the presence of which was defined as genotypic resistance. Treatment-emergent resistance was defined as the presence of genotypic or phenotypic resistance from a post-Baseline sample in the setting of a previously non-resistant Baseline sample. The percentage of participants with treatment-emergent resistance was reported by study year for participants with H3N2 or H1N1pdm09 infections. Only data with evaluable participants were reported.
Time frame: From Baseline (Day 1) to Day 10 (assessed on Days 1, 3, 6, 10) during Study Years 1, 2, 3, 4, 5, 6, 7
Number of Participants With Viral RNA Detected by RT-PCR on Day 1 Among Adults Treated With Oseltamivir
Time frame: Baseline (Day 1)
Number of Participants With Viral RNA Detected by RT-PCR on Day 3 Among Adults Treated With Oseltamivir
Time frame: Day 3
Number of Participants With Viral RNA Detected by RT-PCR on Day 6 Among Adults Treated With Oseltamivir
Time frame: Day 6
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Unnamed facility
Shatin, Hong Kong
Unnamed facility
Rotterdam, Netherlands
Unnamed facility
Sandnes, Norway
Unnamed facility
Krakow, Poland
Number of Participants With Viral RNA Detected by RT-PCR on Day 10 Among Adults Treated With Oseltamivir
Time frame: Day 10
Number of Participants With Viral RNA Detected by RT-PCR on Day 1 Among Children Treated With Oseltamivir
Time frame: Baseline (Day 1)
Number of Participants With Viral RNA Detected by RT-PCR on Day 3 Among Children Treated With Oseltamivir
Time frame: Day 3
Number of Participants With Viral RNA Detected by RT-PCR on Day 6 Among Children Treated With Oseltamivir
Time frame: Day 6
Number of Participants With Viral RNA Detected by RT-PCR on Day 10 Among Children Treated With Oseltamivir
Time frame: Day 10
Time to Non-Detection of Viral RNA
Time to non-detection/viral clearance was the time between symptom onset and the day on which viral RNA was no longer detected, or the last visit date if the participant was not RNA-negative at that visit. Time to non-detection/viral clearance was estimated using Kaplan-Meier analysis and expressed in days.
Time frame: From Baseline (Day 1) to Day 10 (assessed on Days 1, 3, 6, 10)
Time to Non-Detection of Viral RNA Among Participants With H3N2 Infections
Time to non-detection/viral clearance was the time between symptom onset and the day on which viral RNA was no longer detected, or the last visit date if the participant was not RNA-negative at that visit. Time to non-detection/viral clearance was estimated using Kaplan-Meier analysis and expressed in days.
Time frame: From Baseline (Day 1) to Day 10 (assessed on Days 1, 3, 6, 10)
Time to Non-Detection of Viral RNA Among Participants With H1N1pdm09 Infections
Time to non-detection/viral clearance was the time between symptom onset and the day on which viral RNA was no longer detected, or the last visit date if the participant was not RNA-negative at that visit. Time to non-detection/viral clearance was estimated using Kaplan-Meier analysis and expressed in days.
Time frame: From Baseline (Day 1) to Day 10 (assessed on Days 1, 3, 6, 10)
Time to Non-Detection of Viral RNA Among Participants With Influenza B Infections
Time to non-detection/viral clearance was the time between symptom onset and the day on which viral RNA was no longer detected, or the last visit date if the participant was not RNA-negative at that visit. Time to non-detection/viral clearance was estimated using Kaplan-Meier analysis and expressed in days.
Time frame: From Baseline (Day 1) to Day 10 (assessed on Days 1, 3, 6, 10)
Viral Load Among Adults Treated With Oseltamivir
Viral load was determined for those with detectable virus above the lower limit of quantification (LLQ) of 1.82 for influenza A viruses and 1.99 for influenza B viruses. The viral load from each sample was averaged among all participants and expressed in log10 of the number of viral particles per milliliter (log10 vp/mL).
Time frame: Days 1, 3, 6, 10
Viral Load Among Children Treated With Oseltamivir
Viral load was determined for those with detectable virus above the LLQ of 1.82 for influenza A viruses and 1.99 for influenza B viruses. The viral load from each sample was averaged among all participants and expressed in log10 vp/mL.
Time frame: Days 1, 3, 6, 10
Percentage of Participants With Symptom Resolution on Day 6 Comparing Resistant and Susceptible Viruses
Pre-defined mutations in viral RNA were noted, the presence of which was defined as genotypic resistance. Phenotypic resistance was defined as 50% inhibitory concentration (IC50) more than 10-fold higher than the median value for all viruses of the same subtype. Treatment-emergent resistance was defined as the presence of genotypic or phenotypic resistance from a post-Baseline sample in the setting of a previously non-resistant Baseline sample. Susceptible viruses were those that did not exhibit treatment-emergent resistance. The percentage of participants with mild or absent symptoms on Day 6 was reported and stratified by resistant and susceptible viruses.
Time frame: Day 6
Percentage of Participants by Day of Viral RNA First Not Detected Comparing Resistant and Susceptible Viruses
Pre-defined mutations in viral RNA were noted, the presence of which was defined as genotypic resistance. Phenotypic resistance was defined as IC50 more than 10-fold higher than the median value for all viruses of the same subtype. Treatment-emergent resistance was defined as the presence of genotypic or phenotypic resistance from a post-Baseline sample in the setting of a previously non-resistant Baseline sample. Susceptible viruses were those that did not exhibit treatment-emergent resistance. The percentage of participants by earliest post-Baseline test day on which viral RNA was not detected was reported and stratified by resistant and susceptible viruses.
Time frame: Days 3, 6, 10
Percentage of Participants With Resistant Versus Susceptible Viruses by Baseline Viral Load
Pre-defined mutations in viral RNA were noted, the presence of which was defined as genotypic resistance. Phenotypic resistance was defined as IC50 more than 10-fold higher than the median value for all viruses of the same subtype. Treatment-emergent resistance was defined as the presence of genotypic or phenotypic resistance from a post-Baseline sample in the setting of a previously non-resistant Baseline sample. Susceptible viruses were those that did not exhibit treatment-emergent resistance. The mean viral load from each sample was expressed in log10 vp/mL and stratified by resistant and susceptible viruses.
Time frame: Baseline (Day 1)
Total Daily Symptom Score According to Global Assessment by the Investigator Among Adults Treated With Oseltamivir
Symptoms were assessed on Days 1, 6, and 10. The Investigator rated seven symptoms of fever, sore throat, nasal congestion, cough, aches/pains, headache, and fatigue on a scale of 0 (absent/no problem) to 3 (severe/major problem). The global score was calculated as a sum of all individual symptom scores. Global scores may range from 0 to 21, with higher scores indicating worse or more pronounced symptoms.
Time frame: Days 1, 6, 10
Total Daily Symptom Score According to Global Assessment by the Investigator Among Children Treated With Oseltamivir
Symptoms were assessed on Days 1, 6, and 10. The Investigator rated seven symptoms of fever, sore throat, nasal congestion, cough, aches/pains, headache, and energy/tiredness on a scale of 0 (absent/no problem) to 3 (severe/major problem). The global score was calculated as a sum of all individual symptom scores. Global scores may range from 0 to 21, with higher scores indicating worse or more pronounced symptoms.
Time frame: Days 1, 6, 10
Body Temperature Among Adults Treated With Oseltamivir
Body temperature was measured by the Investigator using an oral or tympanic thermometer at Baseline and Day 10. Body temperature at each visit was averaged among all participants and expressed in degrees Celsius.
Time frame: Days 1, 10
Change From Baseline in Body Temperature Among Adults Treated With Oseltamivir
Body temperature was measured by the Investigator using an oral or tympanic thermometer at Baseline and Day 10. The change in body temperature between visits was averaged among all participants and expressed in degrees Celsius.
Time frame: Baseline (Day 1) to Day 10
Body Temperature Among Children Treated With Oseltamivir
Body temperature was measured by the Investigator using an oral or tympanic thermometer at Baseline and Day 10. Body temperature at each visit was averaged among all participants and expressed in degrees Celsius.
Time frame: Days 1, 10
Change From Baseline in Body Temperature Among Children Treated With Oseltamivir
Body temperature was measured by the Investigator using an oral or tympanic thermometer at Baseline and Day 10. The change in body temperature between visits was averaged among all participants and expressed in degrees Celsius.
Time frame: Baseline (Day 1) to Day 10