Background Direct livestock exposure is a risk factor for zoonotic influenza, including H5N1 highly pathogenic avian influenza (HPAI) A virus. But whether living in regions of high poultry and swine production intensity (PPI, SPI) increases risk of exposure to zoonotic influenza viruses independent of occupational livestock contact remains unclear.

Objectives To determine whether livestock workers and community members with no occupational livestock exposure in North Carolina, where poultry and swine production are increasingly co-located, are at higher risk of exposure to zoonotic influenza.

Methods Saliva samples from industrial livestock operation worker (ILO-W), ILO neighbor (ILO-N) and metropolitan area (Metro) households were analyzed for mucosal influenza A (H5N1, H1N1, and H3N2) hemagglutinin (HA) IgA and IgG antibodies to determine associations of PPI, SPI, exposure group, and detection of a swine-specific fecal contamination marker (Pig-2-Bac DNA) with influenza A antibody levels.

Results Residing in the highest PPI and SPI tertile was associated with significantly higher mucosal H5 and H1 HA IgA levels, including among residents without occupational livestock exposure. Households with occupational poultry or swine contact had significantly higher H5 IgA and IgG and H1 IgA levels compared to Metro households. In regression models accounting for clustering at the participant level, log10 anti-H5 HA mucosal IgA increased 0.16 (95% CI: 0.06, 0.27, p<0.005) and 0.10 (95% CI: 0.03, 0.17, p<0.005), per log10 increase in PPI and SPI, respectively, and 0.16 (95% CI: 0.03, 0.19, p<0.02) when Pig-2-Bac DNA was detected on household surfaces.

Conclusions Mucosal H5 HA IgA and IgG and H1 HA IgA were consistently elevated across different metrics of livestock exposure intensity, including residential exposure, occupational contact within a household, and a molecular marker of household swine fecal contamination in a state with intensive poultry and swine production.