H3N2v and other influenza epidemic risk based on age-specific estimates of sero-protection and contact network interactions

Abstract

Cases of a novel swine-origin influenza A(H3N2) variant (H3N2v) have recently been identified in the US, primarily among children. We estimated potential epidemic attack rates (ARs) based on age-specific estimates of sero-susceptibility and social interactions. A contact network model previously established for the Greater Vancouver Area (GVA), Canada was used to estimate average epidemic (infection) ARs for the emerging H3N2v and comparator viruses (H1N1pdm09 and an extinguished H3N2 seasonal strain) based on typical influenza characteristics, basic reproduction number (R(0)), and effective contacts taking into account age-specific sero-protection rates (SPRs). SPRs were assessed in sera collected from the GVA in 2009 or earlier (pre-H1N1pdm09) and fall 2010 (post-H1N1pdm09, seasonal A/Brisbane/10/2007(H3N2), and H3N2v) by hemagglutination inhibition (HI) assay. SPR was assigned per convention based on proportion with HI antibody titre ≥40 (SPR40). Recognizing that the HI titre ≥40 was established as the 50%sero-protective threshold we also explored for ½SPR40, SPR80 and a blended gradient defined as: ¼SPR20, ½SPR40, ¾SPR80, SPR160. Base case analysis assumed R(0) = 1.40, but we also explored R(0) as high as 1.80. With R(0) = 1.40 and SPR40, simulated ARs were well aligned with field observations for H1N1pdm09 incidence (AR: 32%), sporadic detections without a third epidemic wave post-H1N1pdm09 (negligible AR<0.1%) as well as A/Brisbane/10/2007(H3N2) seasonal strain extinction and antigenic drift replacement (negligible AR<0.1%). Simulated AR for the novel swine-origin H3N2v was 6%, highest in children 6-11years (16%). However, with modification to SPR thresholds per above, H3N2v AR ≥20% became possible. At SPR40, H3N2v AR ≥10%, ≥15% or ≥30%, occur if R(0)≥1.48, ≥1.56 or ≥1.86, respectively. Based on conventional assumptions, the novel swine-origin H3N2v does not currently pose a substantial pandemic threat. If H3N2v epidemics do occur, overall community ARs are unlikely to exceed typical seasonal influenza experience. However risk assessment may change with time and depends crucially upon the validation of epidemiological features of influenza, notably the serologic correlate of protection and R(0).

Figure 1. Effective reproduction number (R_eff) according to various scenarios of population immunity by initial basic reproduction number (R₀) assumed.

SPR = Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold; pre-H1N1pdm09: 2009 H1N1 pandemic virus; SPR presented based on PRE-pandemic antibody levels measured in 2009 or earlier; post-H1N1pdm09: 2009 H1N1 pandemic virus; SPR presented based on POST-pandemic antibody levels measured in fall 2010; H3N2v: swine-origin H3N2 variant strain; SPR presented based on antibody levels measured in sera collected in fall 2010; post-Brisbane: a contemporary seasonal human influenza H3N2 virus; SPR presented based post-circulation antibody levels in sera collected in fall 2010; SPR40: the proportion considered sero-protected according to the standard hemagglutination inhibition (HI) titre threshold of 40; ½SPR40: assumes half the individuals meeting SPR40 are considered sero-protected; SPR80: the proportion considered sero-protected according to a hemagglutination inhibition (HI) titre threshold of 80.

Figure 2. Age-stratified epidemic attack rates by scenario and assumed basic reproduction number (R₀ = 1.40). SPR

= Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold; pre-H1N1pdm09: 2009 H1N1 pandemic virus; SPR presented based on PRE-pandemic antibody levels measured in 2009 or earlier; post-H1N1pdm09: 2009 H1N1 pandemic virus; SPR presented based on POST-pandemic antibody levels measured in fall 2010; H3N2v: swine-origin H3N2 variant strain; SPR presented based on antibody levels measured in sera collected in fall 2010; post-Brisbane: a contemporary seasonal human influenza H3N2 virus; SPR presented based post-circulation antibody levels in sera collected in fall 2010; SPR40: the proportion considered sero-protected according to the standard hemagglutination inhibition (HI) titre threshold of 40; ½SPR40: assumes half the individuals meeting SPR40 are considered sero-protected; SPR80: the proportion considered sero-protected according to a hemagglutination inhibition (HI) titre threshold of 80 Overall attack rates are indicated by the horizontal line. Based on simulations using age-specific parameters, these overall attack rates were derived as the total number of infections divided by the total population size.

Figure 3. Age-stratified epidemic attack rates by scenario and assumed basic reproduction number (R₀). SPR

= Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold; H3N2v: swine-origin H3N2 variant strain; SPR presented based on antibody levels measured in sera collected in fall 2010; SPR40: the proportion considered sero-protected according to the standard hemagglutination inhibition (HI) titre threshold of 40; ½SPR40: assumes half the individuals meeting SPR40 are considered sero-protected Overall attack rates are indicated by the horizontal line. Based on simulations using age-specific parameters, these overall attack rates were derived as the total number of infections divided by the total population size.