Risk Factors and Attack Rates of Seasonal Influenza Infection: Results of the Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) Seroepidemiologic Cohort Study

Abstract

Background: Understanding the attack rate of influenza infection and the proportion who become ill by risk group is key to implementing prevention measures. While population-based studies of antihemagglutinin antibody responses have been described previously, studies examining both antihemagglutinin and antineuraminidase antibodies are lacking.

Methods: In 2015, we conducted a seroepidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) titers for seroconversion. We followed participants weekly and performed influenza polymerase chain reaction (PCR) for those reporting influenza-like illness (ILI).

Results: Influenza infection (either HAI or NAI seroconversion) was found in 321 (35% [95% confidence interval, 32%-38%]) of 911 unvaccinated participants, of whom 100 (31%) seroconverted to NAI alone. Young children and Pacific peoples experienced the highest influenza infection attack rates, but overall only a quarter of all infected reported influenza PCR-confirmed ILI, and one-quarter of these sought medical attention. Seroconversion to NAI alone was higher among children aged <5 years vs those aged ≥5 years (14% vs 4%; P < .001) and among those with influenza B vs A(H3N2) virus infections (7% vs 0.3%; P < .001).

Conclusions: Measurement of antineuraminidase antibodies in addition to antihemagglutinin antibodies may be important in capturing the true influenza infection rates.

Figure 1.

Serology and polymerase chain reaction (PCR) testing flow and results among the cohort. Hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) assays were performed for the 911 unvaccinated participants of all ages. Of them, 175 had HAI and NAI seroconversion, 46 HAI alone seroconversion, and 100 NAI alone seroconversion. Among the 321 seroconverters, 156 had influenza-like illness (ILI) symptoms and 109 (70% [109/156]) had swabs taken for influenza PCR, with 50 being positive (46% [50/109]). The rate of ILI was 48.6% (156/321) among HAI or NAI seroconverters and 22.2% (131/590) among nonseroconverters.

Figure 2.

Temporal distribution of influenza-like illness (ILI) and influenza polymerase chain reaction–confirmed ILI and no ILI among the cohort during 27 April–27 September 2015. Influenza viruses were detected continuously during 27 June to 27 September with 2 distinct circulation patterns: A(H3N2) predominated during weeks 26–33, whereas influenza B (mainly B/Victoria lineage) predominated during weeks 34–39. No influenza A(H1N1)pdm09 was detected. ILI is defined as an acute respiratory illness with a history of fever or measured temperature of ≥38°C and cough, and onset within the past 7 days. No ILI refers those participants indicated not having ILI in the weekly text/email “Have you had cough and fever in the previous 7 days?” and also those indicated as having ILI but not verified by nurses.

Figure 3.

Proportions of hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) seroconversion by age groups and by viruses. A, All influenza viruses. B, A(H3N2) virus. C, Influenza B virus. “%HAI” refers to proportion of individuals with HAI seroconversion (≥4-fold HAI titer rise in paired sera with the second titer at least 1:40). “%NAI” refers to proportion of individuals with NAI seroconversion (≥4-fold NAI titer rise in paired sera). “%NAI – %HAI” refers to the difference between NAI and HAI seroconversion rates by subtraction.