ba Kelly 2011.

Methods	The Western Australian Influenza Vaccine Effectiveness (WAIVE) study evaluated the protective effect of inactivated influenza vaccination in children aged 6 to 59 months, by means of a prospective case‐control study conducted in general practices and a hospital emergency department. Eligible participants were tested for influenza and a range of other common respiratory viruses. Influenza vaccine effectiveness (VE) against laboratory‐confirmed influenza was estimated with cases defined as children with an ILI who tested positive and controls as those with an ILI who tested negative for influenza virus.
Participants	Participants were children aged 6 to 59 months presenting with an ILI and from whom swabs had been taken for laboratory testing.   ILI definition used in this study was “documented fever with oral (or aural) temperature 38°C (or axillary temperature 37.5°C), with at least 1 acute respiratory symptom or sign. Children were recruited if they had met the case definition for an ILI within the previous 72 hours”.   All emergency department participants were recruited from the Emergency Department of Princess Margaret Hospital for Children, the only paediatric tertiary hospital in Western Australia. Children were also recruited from general practices in metropolitan Perth and Kalgoorlie.   Those testing positive for influenza viruses were identified as cases, while those testing negative for influenza viruses were identified as controls.   Cases and controls were recruited when they presented with an ILI, but their case or control status was not known at the time.
Interventions	Informed consent was obtained, parents were provided with a questionnaire to complete, which included demographic data, influenza vaccinations received in 2008 and previous years, and any underlying chronic illnesses. Vaccine status was validated for 87% of all participants with the vaccine provider of the child. Children were defined as FV if they had received 2 age‐appropriate doses of vaccine at least 21 days apart and more than 14 days before ILI onset in 2008. Children were also defined as FV if they had received at least 2 previous doses of influenza vaccine in any year and 1 dose of the age‐appropriate vaccine in 2008. Children who received no vaccine in 2008 were counted as UV, and all other children were defined as partially vaccinated.
Outcomes	Laboratory “All samples were then tested by real‐time PCR directed to specific targets in the matrix genes of influenza A and B and the H1 and H3 genes of influenza A.13,14 Samples were also cultured for influenza viruses using centrifuge‐enhanced inoculation of Madin‐Darby canine kidney cells and those which were culture positive were referred to the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne, where detailed antigenic characterisation was performed. In addition to influenza viruses, the swabs were tested by PCR for the presence of rhinoviruses, respiratory syncytial viruses, parainfluenza virus types 1, 2 and 3, human metapneumoviruses and enteroviruses. Viral culture for adenoviruses was also performed using diploid lung fibroblast cells and monitoring for cytopathic effect”
Funding Source	Government
Notes	The authors conclude that "A total of 75 children were enrolled from general practices and 214 through the emergency department, with 12 (27%) and 36 (17%), respectively, having laboratory‐confirmed influenza. Using all the influenza negative controls, the adjusted VE was 58% (95% confidence interval, 9–81). When controls were limited to those with another virus present, the adjusted VE was 68% (95% confidence interval, 26–86). VE estimates were higher when controls included only those children with another respiratory virus detected". A well‐reported and well‐conducted study; the only concern is about the role of confounding variables selected to adjust estimates.
Risk of bias
Bias	Authors' judgement	Support for judgement
CC‐Case Selection	Low risk	Independent validation
CC‐Control Selection	Low risk	Drawn from the same population ‐ hospital control
CC‐Comparability	Unclear risk	Adjustment by confounders
CC‐Exposure	Low risk	Secure record ‐ interview
Summary assessments	Unclear risk	Plausible bias that raises some doubts about the results