Distinct influenza surveillance networks and their agreement in recording regional influenza circulation: Experience from Southeast Michigan

IntroductionIn Southeast Michigan, active surveillance studies monitor influenza activity in hospitals, ambulatory clinics, and community households. Across five respiratory seasons, we assessed the contribution of data from each of the three networks towards improving our overall understanding of regional influenza circulation.MethodsAll three networks used case definitions for acute respiratory illness (ARI) and molecularly tested for influenza from research-collected respiratory specimens. Age- and network-stratified epidemic curves were created for influenza A and B. We compared stratified epidemic curves visually and by centering at seasonal midpoints.ResultsAcross all seasons (from 2014/2015 through 2018/2019), epidemic curves from each of the three networks were comparable in terms of both timing and magnitude. Small discrepancies in epidemics recorded by each network support previous conclusions about broader characteristics of particular influenza seasons.ConclusionInfluenza surveillance systems based in hospital, ambulatory clinic, and community household settings appear to provide largely similar information regarding regional epidemic activity. Together, multiple levels of influenza surveillance provide a detailed view of regional influenza epidemics, but a single surveillance system—regardless of population subgroup monitored—appears to be sufficient in providing vital information regarding community influenza epidemics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172297/1/irv12944.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172297/2/irv12944_am.pd

Intrahost diversity in samples from the 2007–2008 season.

<p>(A) Histogram of the number of iSNV at a given frequency. Bin width = 0.01. (B) Histogram of the number of samples in which each iSNV is found. Arrows indicate bars with one SNV, which are hard to discern in the histogram. These polymorphic SNV, at PB2 position 900 and PA position 515 respectively, were found at 4–6% frequency within hosts and in similar numbers of individuals across vaccination groups. (C) Number of HA iSNV per sample stratified by pre-season HAI titer. >40 = serologically immune, <40 = not serologically immune. (D) Number of NA iSNV per sample stratified by pre-season NAI titer. ≥40 = serologically immune, <40 = not serologically immune.</p

Vaccination has minimal impact on the intrahost diversity of H3N2 influenza viruses

<div><p>While influenza virus diversity and antigenic drift have been well characterized on a global scale, the factors that influence the virus’ rapid evolution within and between human hosts are less clear. Given the modest effectiveness of seasonal vaccination, vaccine-induced antibody responses could serve as a potent selective pressure for novel influenza variants at the individual or community level. We used next generation sequencing of patient-derived viruses from a randomized, placebo-controlled trial of vaccine efficacy to characterize the diversity of influenza A virus and to define the impact of vaccine-induced immunity on within-host populations. Importantly, this study design allowed us to isolate the impact of vaccination while still studying natural infection. We used pre-season hemagglutination inhibition and neuraminidase inhibition titers to quantify vaccine-induced immunity directly and to assess its impact on intrahost populations. We identified 166 cases of H3N2 influenza over 3 seasons and 5119 person-years. We obtained whole genome sequence data for 119 samples and used a stringent and empirically validated analysis pipeline to identify intrahost single nucleotide variants at ≥1% frequency. Phylogenetic analysis of consensus hemagglutinin and neuraminidase sequences showed no stratification by pre-season HAI and NAI titer, respectively. In our study population, we found that the vast majority of intrahost single nucleotide variants were rare and that very few were found in more than one individual. Most samples had fewer than 15 single nucleotide variants across the entire genome, and the level of diversity did not significantly vary with day of sampling, vaccination status, or pre-season antibody titer. Contrary to what has been suggested in experimental systems, our data indicate that seasonal influenza vaccination has little impact on intrahost diversity in natural infection and that vaccine-induced immunity may be only a minor contributor to antigenic drift at local scales.</p></div

Samples analyzed over three FLU-VACS seasons.

<p>Samples analyzed over three FLU-VACS seasons.</p

Phylogenetic trees of HA and NA consensus sequences from the 2007–2008 season.

<p>Maximum likelihood trees of HA (left) and NA (right) with tips coded by vaccine status and pre-season HAI (left; blue >40, magenta <40) or NAI (right; blue ≥40, magenta <40) titer. HAI (left) and NAI (right) titers are shown on tips as well. Outgroups are HA (EU103823.1) and NA (CY114383.1) for the vaccine strain A/Wisconsin/67/2005. Bootstrap values (n = 1000 bootstraps) are shown and nodes with bootstrap values <50 are collapsed for easier visualization.</p

Temporal patterns of intrahost diversity.

<p>Number of genome-wide iSNV per sample (y-axis) by day of symptoms (x-axis) stratified by (A) recipients of IIV, magenta; LAIV, blue; placebo, white (B) HAI >40, magenta; HAI <40, white (C) NAI ≥40, magenta; NAI <40, white. Mean number of iSNV in each group is indicated (bar).</p