ba Staat 2011a.

Methods	Case‐control study assessing the efficacy of the trivalent inactivated influenza vaccine against laboratory‐confirmed influenza for the 2005–06 and 2006–07 influenza seasons. Vaccination rates among children 6 to 59 months of age with ARI or fever and laboratory‐confirmed influenza were compared with influenza test‐negative controls who also had a medically attended ARI. The design is based on active surveillance system in which the influenza vaccination status of children with laboratory‐confirmed influenza was compared with that of laboratory‐confirmed influenza‐negative matched controls.
Participants	Inpatient Children were enrolled 5 days a week after admission to surveillance hospitals. Eligible children were county residents younger than 5 years of age who were admitted with signs or symptoms of ARI. Children were excluded if they had fever and neutropenia associated with chemotherapy, were hospitalised  in the prior 4 days, transferred from another surveillance hospital, or were newborns never discharged from the hospital.   Outpatient settings Prospective surveillance of county children presenting with ARI to selected clinics and EDs was conducted during the 2 seasons. Study personnel enrolled children in the clinics and the EDs on specified surveillance days using similar inclusion and exclusion criteria to inpatient enrolment. Children were enrolled 1 or 2 days per week in 1 to 4 paediatric clinics per county and were enrolled 3 or 4 days per week in the EDs.   Description of cases and controls Children whose specimens tested positive for influenza were eligible to be cases, and those who tested negative were eligible to be controls.   To ensure that all children included in this study were eligible for vaccination based on current recommendations, the following parameters were used. Since the minimum age to receive a primary influenza vaccination is 24 weeks (168 days), followed by a second vaccination a minimum of 24 days later (192 days), and the child is considered protected 2 weeks following the final dose (206 days), 206 days was used as the lower age limit for this study.   The upper age limit was 59 months at the onset of symptoms. The onset of the child’s symptoms must have occurred during influenza season for each geographic site. The start of the influenza season was defined as the occurrence of 1 or more positive influenza specimens in 2 consecutive weeks through local research or hospital laboratories at each site. The end of the influenza season was defined as the absence of 1 or more positive specimen(s) of influenza in 2 consecutive weeks.   Control children were matched to case children by disease onset date (plus or minus 7 days), clinical setting (inpatient, ED, or clinic), geographic site (Nashville, Cincinnati, Rochester), and age (6 to 23 months, 24 to 59 months). The number of matched controls per case varied from 1 to 4 (1 control  (28%), 2 controls (15%), 3 controls (12%), and 4 controls (34%)). For 18 children, 8 from the ED and 10 from outpatient practices, only 1 control that matched 2 cases was available, so both cases were matched to the same control.
Interventions	Exposure Influenza vaccination status at the time of the ARI visit was determined through a telephone call or fax to the child’s primary care practice and subsequent extraction of influenza vaccination data from the child’s primary care medical record and/or the state immunisation registry, if available. Children were classified as FV if vaccinated according to ACIP guidelines, which included either 2 doses in the current season administered ≥ 24 days apart, or at least 1 vaccine dose in a previous influenza season and 1 dose in the current season, administered ≥ 14 days before ARI onset. Children were classified as being partially vaccinated if they received only 1 of the 2 recommended doses in the current season, ≥ 14 days before ARI onset or 2 vaccinations in the current season with the second dose administered within 14 days of ARI onset or < 24 days after the first dose. Children were classified as UV if they received no influenza vaccine doses during the study season or received the first of 2 recommended doses within 14 days before ARI onset during the study season.
Outcomes	Laboratory Nasal and throat swabs obtained from each enrolled child were tested for influenza at each site’s research laboratory with standardisation of assays across sites using reverse transcription‐polymerase chain reaction assays, as described previously. A subset of children had viral cultures done. A specimen was defined as being influenza‐positive if viral culture or duplicate PCR assays were positive for influenza A or B. No children had a positive culture for influenza and a negative PCR, while 9 children with a negative culture had a positive PCR for influenza.
Funding Source	Government
Notes	The authors conclude that "Each year, young children experience high rates of hospitalizations, ED visits and outpatient visits due to influenza. We found that full vaccination with the trivalent inactivated vaccine prevented nearly 60% of medically attended influenza visits across 2 influenza seasons for individual and combined age groups of children. An estimated 5% to 10% of children have an influenza‐related ARI visit each year and the visit often results in an antibiotic prescription [1,2,27]. This study and others’ suggest that widespread influenza vaccination of children will have a major impact on health care utilization. Our study supports recommendations from the CDC to vaccinate young children against influenza disease and highlights the importance of full vaccination, since partial vaccination showed no significant VE". Well‐reported and well‐conducted study; the only concern is about real effect of the matching procedure adopted by the authors. We are uncertain as to whether it assures good comparability between cases and control.
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
CC‐Comparability	Unclear risk	Matched
CC‐Exposure	Low risk	Secure record and interview
Summary assessments	Unclear risk	Plausible bias that raises some doubts about the results