Figure 4. The proportion of influenza positive samples typed as A(H3N2) increases with antigenic drift.

(A-B) Seasonal A(H3N2) subtype dominance increases with (A) hemagglutinin (H3) and (B) neuraminidase (N2) epitope distance. Seasonal epitope distance is the mean epitope distance between viruses circulating in the current season ${\displaystyle t}$ and viruses circulating in the prior season (${\displaystyle t}$ - 1) or two prior seasons ago (${\displaystyle t}$ - 2). Distances were scaled to aid in direct comparison of evolutionary indicators. Point color indicates the dominant influenza A virus (IAV) subtype based on CDC influenza season summary reports (red: A(H3N2), blue: A(H1N1), purple: A(H1N1)pdm09, orange: A(H3N2)/A(H1N1)pdm09 co-dominant), and vertical bars are 95% confidence intervals of regional estimates (pre-2009 seasons: 9 regions; post-2009 seasons: 10 regions). Seasonal mean A(H3N2) dominance was fit as a function of H3 or N2 epitope distance using Beta GLMs with 1000 bootstrap resamples. In (A) and (B), the dashed black line represents the mean regression fit, and the gray shaded band shows the 95% confidence interval, based on 1000 bootstrap resamples. The R² and associated p-value from the mean regression fit are in the bottom right section of each plot. (C–D) Regional patterns of influenza type and subtype incidence during two seasons when A(H3N2) was nationally dominant. Pie charts represent the proportion of influenza positive samples typed as A(H3N2) (red), A(H1N1) (blue), or B (green) in each HHS region. The sizes of regional pie charts are proportional to the total number of influenza positive samples. Data for Region 10 (purple) are not available for seasons prior to 2009. (C) Widespread A(H3N2) dominance during 2003–2004 after the emergence of a novel antigenic cluster, FU02 (A/Fujian/411/2002-like strains). (D) Spatial heterogeneity in subtype circulation during 2007–2008, a season with low A(H3N2) antigenic novelty relative to the prior season.

Figure 4—figure supplement 1. Regional patterns of influenza type and subtype circulation during seasons 1997–1998 to 2018–2019.

Pie charts represent the proportion of influenza positive samples that were typed as A(H3N2), A(H1N1) or A(H1N1)pdm09, and B in each HHS region. Data for Region 10 (purple) are not available for seasons prior to 2009.