Questioning aerosol transmission of influenza.

To the Editor

We have reviewed the literature cited in Tellier’s Review of Aerosol Transmission of Influenza A Virus () and disagree that it supports the conclusions drawn regarding the importance of aerosols in natural influenza infection. In certain cited studies, researchers recovered viable virus from artificially generated aerosols; this is not evidence that aerosol transmission leads to natural human infection (,). By standard definitions, the rarity of long-range infections supports the conclusion that effective aerosol transmission is absent in the natural state () (www.cdc.gov/ncidod/dhqp/gl_isolation_hicpac.html). The superior efficacy of inhaled versus intranasal zanamivir is referenced as support for the idea that the lower respiratory tract is the preferred site of influenza infection; however, 1 study cited is insufficiently powered, and the other 2 do not compare the intranasal and inhaled routes (–). The major site of deposition of inhaled zanamivir is the oropharynx (77.6%), not the lungs (13.2%) (www.gsk.ca/en/products/prescription/relenza_pm.pdf). In another flawed study (), study participants naturally infected with wild-type virus are compared with study participants experimentally infected with an attenuated strain.

In a review of such relevance, critical analysis of confounding factors is necessary. The Alaska Airlines outbreak () is presented as proof of airborne influenza transmission; however, droplet/contact transmission remains plausible because passenger movement was not restricted and the index patient was seated in high-traffic area. In the Livermore Hospital study (), serious confounders such as bed arrangements, number of influenza exposures, patient mix, and ventilation were not accounted for.

We encourage readers of Teller’s article to review the relevant primary literature. We believe that the only reasonable conclusion that can be drawn at this time is that aerosol transmission does not play a major role in natural influenza epidemiology. Whether aerosols play any role in the transmission of influenza is a question demanding an answer; it is clear that we do not yet have that answer.

Coughing and sneezing during influenza produce virus-containing aerosols. In the laboratory, influenza virus in homogeneous aerosols, free of large droplets, can infect volunteers at very small doses; studies of infectivity decay in aerosols show persistence for hours. These observations required the generation of artificial aerosols but were performed under conditions that do not enhance stability or virulence (,). Therefore, they have great relevance for natural infections.

The scarcity of infections that are transmitted long range in well-ventilated areas does not rule out infectivity of aerosol-size particles near patients. That only 13% of inhaled zanamivir is deposited in the lungs is not important: after inhalation, the zanamivir concentration throughout the respiratory tract is >10 μmol/L, orders of magnitude above the 50% inhibitory concentration (). Intranasal zanamivir is protective against large droplets (), which are trapped in the nose (). The requirement for inhaled zanamivir in natural infections (,) points to aerosol contribution and to the lower respiratory tract as the preferred site.

Little et al. () compared the severity of natural illness caused by H3N2 strains from 1974 and 1975 to that caused by experimental intranasal inoculation from H3N2 strains from 1972, 1974, and 1975. The challenge strains underwent few passages; characterizing them as "attenuated" is incorrect.

Although large droplets probably accounted for some cases in the Alaska Airlines outbreak (), this outbreak was remarkable for its high attack rate (72%) and for deficient ventilation, which would increase transmission by aerosols but not by large droplets. Passengers with influenza are common, yet with proper ventilation such an attack rate is uncommon.

During the Livermore Hospital study (), respiratory infections other than influenza occurred in both groups. It was assumed that visitors and staff would provide equivalent introductions of the virus during the several months of the study; 4 study participants in the irradiated building seroconverted, but the virus did not propagate. The concern by Lemieux and colleagues about ventilation is odd because it would affect mostly aerosol transmission.

I concur with encouraging readers to review the original references. They make a compelling case for the importance of aerosol transmission. In contrast, no convincing data rule it out.