Early exposure to influenza A(H3N2) viruses and vaccine effectiveness against A(H3N2)-associated illness in U.S. children

  • Vaccine preventable diseases
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Background:
During 2017–18, influenza vaccine effectiveness (VE) against A(H3N2) illness was highest among children <5 years compared to all other ages. The emergence of antigenically distinct influenza A(H3N2) viruses in 2014–15 provided an opportunity to explore potential effects of first virus infection on vaccine effects. We compared VE against influenza A(H3N2) during 2016–17 and 2017–18 among children born after and before 2014.

Methods:
Outpatient children aged 6 months–17 years with acute respiratory illness with cough were enrolled in the United States Influenza VE Network and tested for influenza infection by RT-PCR. Vaccination status was derived through medical records and immunization registries. We used a test-negative, case-control design to estimate VE and 95% confidence intervals (CI) from logistic regression, adjusting for surveillance site, enrollment month, presence of high-risk condition, and race/ethnicity. Cohorts were defined by birth after or before June 2014, before the 2014– 15 influenza season where a new A(H3N2) predominated; we assumed exposure to the new A(H3N2) virus among children born after June 2014.

Results:
During 2016–17, among 2,545 children, 445 (18%) tested positive for A(H3N2) and 1,809 (71%) tested negative. The remainder tested positive for co-infections. VE against A(H3N2) did not differ among children born after June 2014 and among those born before June 2014 [49% (95% CI: -12%, 77%) vs. 43% (27%, 55%); interaction P<0.75]. During 2017–18, among 2,936 patients, 631 (22%) tested positive for A(H3N2), and 1,852 (63%) tested negative. VE against A(H3N2) was 59% (36%, 74%) among children born after June 2014 versus 20% (-1%, 37%) among those born before June 2014 (interaction P<0.01).

Conclusion:
We did not consistently see differences in VE against A(H3N2) between children potentially exposed to different A(H3N2) viruses. However, error in exposure assignment to A(H3N2) viruses and only a few seasons since the emergence of the new A(H3N2) viruses limit our interpretation. Alternative explanations for age-related differences will also be explored.

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