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. 2018 May 24;13(5):e0197504.
doi: 10.1371/journal.pone.0197504. eCollection 2018.

Incidence of Influenza A(H3N2) Virus Infections in Hong Kong in a Longitudinal Sero-Epidemiological Study, 2009-2015

Free PMC article

Incidence of Influenza A(H3N2) Virus Infections in Hong Kong in a Longitudinal Sero-Epidemiological Study, 2009-2015

Vivian W I Wei et al. PLoS One. .
Free PMC article


Background: Many serologic studies were done during and after the 2009 influenza pandemic, to estimate the cumulative incidence of influenza A(H1N1)pdm09 virus infections, but there are few comparative estimates of the incidence of influenza A(H3N2) virus infections during epidemics.

Methods: We conducted a longitudinal serologic study in Hong Kong. We collected sera annually and tested samples from 2009-13 by HAI against the A/Perth/16/2009(H3N2) virus, and samples from 2013-15 against the A/Victoria/361/2011(H3N2) virus using the hemagglutination inhibition (HAI) assay. We estimated the cumulative incidence of infections based on 4-fold or greater rises in HAI titers in consecutive sera.

Results: There were four major H3N2 epidemics: (1) Aug-Oct 2010; (2) Mar-Jun 2012; (3) Jul-Oct 2013; and (4) Jun-Jul 2014. Between 516 and 619 relevant pairs of sera were available for each epidemic. We estimated that 9%, 19%, 7% and 7% of the population were infected in each epidemic, respectively, with higher incidence in children in epidemics 1 and 4.

Conclusions: We found that re-infections in each of the four H3N2 epidemics that occurred from 2010 through 2014 were rare. The largest H3N2 epidemic occurred with the lowest level of pre-epidemic immunity.

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: BJC has received research funding from Sanofi Pasteur for a study of influenza vaccine effectiveness. BJC is a Section Editor of PLoS ONE. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. The authors report no other potential conflicts of interest.


Fig 1
Fig 1. Timeline of our study rounds and community influenza virus activity.
In total we collected blood in seven rounds, with each of the four numbered H3N2 epidemics being neatly bracketed by two consecutive rounds of blood draws. The y-axis shows weekly influenza virus activity in Hong Kong from 2009 to 2014, measured for each influenza type/subtype as the weekly proportion of outpatient consultations associated with influenza-like-illness in sentinel outpatient clinics multiplied by the weekly proportions of laboratory specimens testing positive for influenza A(H3N2), A(H1N1)pdm09 and B viruses respectively. For each type/subtype the activity level should correlate with incidence of infections within an epidemic, but changes in consultation behaviors between epidemics (e.g. in 2009/10) may also influence observed ‘activity’ levels.
Fig 2
Fig 2. Declines in HAI titers against influenza A/Perth/16/2009(H3N2) and A/Victoria/361/2011(H3N2) virus after infection.
In each panel the black regression lines indicate the rates of antibody waning from a fitted log-linear model, and the grey lines indicate the geometric mean titers at the center of each time point that sera were collected. There were 126 and 44 participants infected against A/Perth/16/2009(H3N2) and A/Victoria/361/2011(H3N2) respectively.
Fig 3
Fig 3. Correlation between HAI titers and protection against influenza A(H3N2) virus infection.
The upper panel shows the number of uninfected and infected persons in each pre-epidemic titer range. The lower panel shows the estimated degree of protection associated with higher pre-epidemic titers, calculated as the relative risk reduction compared with the risk at a pre-epidemic HAI titer <10.
Fig 4
Fig 4. Comparison between susceptibility and age-standardized cumulative incidence of infection in four influenza A(H3N2) epidemics.
The susceptibility index was calculated as 1 minus relative risk reduction compared with the risk at per-epidemic HAI titer <10. The cumulative incidence of infection was standardized by age to the Hong Kong population in 2010. Each text 1 to 4 corresponds to epidemics 1 to 4 respectively.

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