1. Influenza Vaccine Effectiveness Against Pediatric Deaths: 2010-2014
Brendan flannery et al.
Article review by Andrea Prinzi

2. Background
In the US, annual vaccination of children is recommended in order to prevent severe complications/adverse events
Pediatric Flu deaths are uncommon, but they do occur
From 1976 – 2007, Influenza was estimated to account for >100 deaths in children and adolescents annually
Influenza deaths in children <18 became nationally notifiable in Since then:
37 children died during the season
358 during the 2009 pandemic

3. Background Continued
Previous reports have demonstrated low Influenza vaccination rates among pediatric deaths
Evidence that shows the effectiveness of Influenza vaccination in preventing Influenza-related deaths is needed

4. Methods Case-cohort design (screening method)
Determining vaccination status
Review of information from medical records, healthcare provider, state or community immunization records, parental report or coroners report.
Children considered vaccinated (full or partial) if >/= 1 dose of seasonal flu vaccine was received >14 days prior to onset of illness
Partial vaccination was defined at receiving one dose when the state health department recommended two
Case-cohort design (screening method)
Cases were deaths in US residents <18 y/o with lab confirmed Influenza that was reported to the Influenza Associated Pediatric Mortality Surveillance System
Data obtained from forms: demographics, state of residence, lab results, underlying conditions and flu vaccine status

5. Influenza Vaccination Coverage in Cohorts
Three sources of Flu vaccination coverage were used:
National Immunization Survey – FLU (NIS-FLU)
National telephone survey of households with children 6 months- 17 years that provides national a state-level estimates of Flu vaccination
National Health Interview Survey (NHIS)
In-person household survey that provides flu vaccination info on patients aged 6 months to 17 years and without underlying medical conditions
Marketscan commercial claims and Encounters Database
Estimates based on commercial insurance claims

6. Results
Analysis included 358 pediatric Flu-related deaths that occurred from
Children were aged 6 months – 17 years
Deaths were reported from 43 states
Vaccine status was unknown for 19% of these children
In 291 deaths of children with known vaccination status, 75 (26%) were considered fully vaccinated
19% received live-attenuated Flu vaccine, 81% received inactivated Flu vaccines
Black non-Hispanic children who died had significantly lower vaccination rates compared with white children who died (P <.05)
Among 31 deaths in vaccinated children, 52% were partially vaccinated

7. Comparison of vaccination coverage among influenza-associated pediatric deaths and comparison cohorts during 4 influenza seasons, according to month of death. Number of deaths shown in parentheses

8. Figure 1 Summarized:
Average Influenza vaccine coverage among comparison cohorts in the month preceding case illness onset was higher than vaccinated proportions among pediatric deaths for most months.

10. Table 2 Summary
Among deaths in children with known vaccination status, children who died had lower vaccination uptake for all age categories, seasons, and infecting virus type than the NIS-Flu cohort.
Overall, vaccination coverage was 48% among NIS-Flu comparison cohorts
Estimated VE against death was 65%
By season, VE ranged from 54% to 80%
VE estimates were similar against death for Influenza A and B

11. Looking at Vaccination Uptake
Table three shows that vaccination uptake among pediatric deaths was lower than average coverage in the NHIS cohort with or without high-risk conditions.
Estimated VE was 51% to 67% in children with underlying conditions
VE’s were only statistically significant for children 5-12 years old
Estimated VE was 65% for children without underlying medical conditions

13. Sensitivity Analysis (Table 5)
Treating deaths with unknown vaccination status as unvaccinated :
VE for NIS increased to 74%
VE for NHIS increased to 73% for children without underlying conditions
VE increased to 50% for Marketscan cohort for children without underlying conditions
Assuming 10% overestimation of vaccine status by parental report:
VE went to 56% in the NIS-Flu cohort
VE went to 58% in the NHIS cohort (no high risk)

15. Conclusions
Best estimates based on NHIS survey data suggest that vaccination reduced the risk of Influenza-related death by half among children with high-risk conditions and nearly two-thirds in children without underlying conditions.
Despite the high prevalence of underlying conditions (53%), only 1 in 4 of children who died from laboratory confirmed Influenza had been vaccinated. Vaccination coverage needs to be increased, especially among high-risk children!
This is the first study to use laboratory outcomes to investigate VE
Results of this analysis support the use of VE to estimate deaths averted by Flu vaccination