Relative Contributions of Four Exposure Pathways to Influenza Infection Risk

The relative contribution of four influenza virus exposure pathways—(1) virus-contaminated hand contact with facial membranes, (2) inhalation of respirable cough particles, (3) inhalation of inspirable cough particles, and (4) spray of cough droplets onto facial membranes—must be quantified to determine the potential efficacy of nonpharmaceutical interventions of transmission. We used a mathematical model to estimate the relative contributions of the four pathways to infection risk in the context of a person attending a bed-ridden family member ill with influenza. Considering the uncertainties in the sparse human subject influenza dose-response data, we assumed alternative ratios of 3,200:1 and 1:1 for the infectivity of inhaled respirable virus to intranasally instilled virus. For the 3,200:1 ratio, pathways (1), (2), and (4) contribute substantially to influenza risk: at a virus saliva concentration of 10⁶ mL^?1, pathways (1), (2), (3), and (4) contribute, respectively, 31%, 17%, 0.52%, and 52% of the infection risk. With increasing virus concentrations, pathway (2) increases in importance, while pathway (4) decreases in importance. In contrast, for the 1:1 infectivity ratio, pathway (1) is the most important overall: at a virus saliva concentration of 10⁶ mL^?1, pathways (1), (2), (3), and (4) contribute, respectively, 93%, 0.037%, 3.3%, and 3.7% of the infection risk. With increasing virus concentrations, pathway (3) increases in importance, while pathway (4) decreases in importance. Given the sparse knowledge concerning influenza dose and infectivity via different exposure pathways, nonpharmaceutical interventions for influenza should simultaneously address potential exposure via hand contact to the face, inhalation, and droplet spray.