In this week’s Science magazine Stephen Morse calls attention to what we have been saying here for a long time. We don’t really know how influenza spreds from person to person. A recent review of the aerosol transmission route by Tellier in Emerging Infectious Diseases provides some additional information of interest.
There are four possible modes of transmission: aerosol, large droplet, direct contact via inanimate objects (called fomites in epidemiological jargon) and the gastrointestinal route. At this point we know very little about the gastrointestinal route, although some H5N1 cases suggest this is possible. Almost all the literature repeats the conventional view that “large droplet” transmission predominates, although, as Tellier points out (as have we), there is little evidence to support it. On the contrary, Tellier marshals some cogent arguments to suggest aerosols are the most important mode.
Some quick background. Solids or liquids particles suspended in a gas or mixture of gases (such as the air) is called an aerosol. If the particles are too large or heavy they no longer remain suspended and fall out rapidly. This is a well researched area in industrial hygiene. Particles greater than 100 µm (microns or millionths of a meter) drop out in a few seconds. At 10 µm it takes a quarter of an hour, while at 5 µm it is over an hour. At less than 3 µm, the particles essentially remain suspended indefinitely. this means they can also be transported over long distances, while the heavier particles fall out within a few meters of emission.
Suspension time is not the only issue. Small particles are able to negotiate the twists and turns of the upper respiratory tract to get into the lower regions of the lung. Large droplets settle out fast and even if breathed, don’t get down into the lungs, staying instead in the nose and throat area. So for virus laden particles, size matters.
A good cough or sneeze sprays out a tremendous amount of potentially infectious material. Here is the classic photo of a sneeze. This person is not some olympic sneezer. This is what it really looks like when photographed with appropriate techniques. Not pretty.
One thing you can see here are very large droplets. What you can’t see, because they are below the resolution of the photo, are any aerosols, particles less than 3 µm in size. Even some droplets of larger diameters can quickly reduce to aerosol size by drying. This can happen in seconds because of the large surface area to volume ratio of these particles. Conversely, these particles if reintroduced in a region of very high humidity (like your lower respiratory tract) can grow in size by absorbing moisture. Thus they effectively become trapped in the lower regions. You don’t just breathe them out again.
Respiratory secretions from someone infected with influenza have been shown to have high numbers of viral particles. The peak shedding is said to be on day two or three for seasonal influenza. We don’t know if the same is true for H5N1 infection. The drier the air the longer the virus remains viable. In experimental studies, the virus has stayed viable for up to 24 hours. But humid air is bad for the virus, it appears. Its infectivity decreases much more rapidly when relative humidity was greater than 40%. There is speculation that the seasonal nature of influenza is related to the drier air in fall and winter, although this is probably not the only factor.
None of this tells us whether large droplets or aerosols are the main mode of transmission, however. Experimental studies in animals and humans, with carefully controlled exposures of known size, strongly suggest that aerosols are the operative factor, however. The potency of virus in aerosols was also much larger than when volunteers were infected by intranasal inoculation. Tellier interprets the data to say the principal site of infection in humans is in the lower respiratory tract via aerosols. He notes that when zanamivir (Relenza) is given as a nose spray it is not effective but when given by inhalation so that it gets into the lower respiratory tract it is.
Tellier’s review of the scant epidemiological data is also quite interesting. Here is his account of the Livermore Veterans Administration Hospital outbreak during the 1957-58 panemic:
The study group consisted of 209 tuberculous patients confined during their hospitalization to a building with ceiling-mounted UV lights; 396 tuberculous patients hospitalized in other buildings that lacked these lights constituted the control group. Although the study group participants remained confined to the building, they were attended to by the same personnel as the control group, and there were no restrictions on visits from the community. Thus, it was unavoidable at some point that attending personnel and visitors would introduce influenza virus in both groups. During the second wave of the pandemic, the control group and the personnel sustained a robust outbreak of respiratory illness, shown retrospectively by serology to be due to the pandemic strain influenza A (H2N2), whereas the group in the irradiated building remained symptom free. The seroconversion rate to influenza A (H2N2) was 19% in the control group, 18% in personnel, but only 2% in the study group.
Whereas UV irradiation is highly effective in inactivating viruses in small-particle aerosols, it is ineffective for surface decontamination because of poor surface penetrations. It is also ineffective for large droplets because the germicidal activity sharply decreases as the relative humidity increases. Furthermore, because the installation of UV lights was set up in such a way as to decontaminate the upper air of rooms only, large droplets would not have been exposed to UV, whereas aerosols, carried by thermal air mixing, would have been exposed. So in effect in this study only the aerosol route of infection was blocked, and this step alone achieved near complete protection. (cites omitted; Tellier, Emerging Infectioius Diseases)
There are still many questions about the spread of ordinary influenza and even more about H5N1. Tellier believes the existing evidence is more than adequate to demand the use of N95 respirators in health care institutions, not just during “aerosolizing procedures” as currently recommended by CDC but anywhere where there is coughing and sneezing from infected patients. We find it curious that he says nothing about using ultraviolet light germicidal irradiation (UVGI) units in healh care facilities since his evidence seemed to suggest it was useful and there is no comparable evidence for N95 masks. The role of hand hygiene and various kinds of personal distancing still remains unknown. Morse’s plea for more investment in research in this area seems more than responable.
The debates will continue, even as a great deal of poorly founded advice is being handed out witout much questioning. Much of it, like advocating cough and hand hygiene, are at worst harmless and at best will have some effectiveness and not just for influenza. But none of it is obvious and some of it — the contention that surgical masks are sufficient because transmission is by large droplet — is potentially harmful.
The depths of our ignorance in this age of sophisticated molecular biology is truly impressive.