Effect Measure

How does flu spread?

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.

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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.

Comments

  1. #1 crfullmoon
    November 13, 2006

    Those pesky, “unknown unknowns”….

  2. #2 Marissa
    November 13, 2006

    Good post, revere, didn’t know about humidity or those UV light experiments. I’ve always thought there’s an aerosol component, but thought this is a function to some extent of what the patient does.

  3. #3 cabingirl
    November 13, 2006

    So…I wonder, would humidifiers in every room occupied (sick rooms included), during low humidity winter months, reduce the aerosol component within a structure?

  4. #4 revere
    November 13, 2006

    cabingirl: Good question. Note that some viruses (not flu) like high humidity. There’s always a catch.

  5. #5 Mathematician
    November 13, 2006

    Question I’ve wondered about: how does the transmission before symptoms begin compare with that afterwards? A lot of us have worried about the fact that people are infectious with flu before they show symptoms. But by definition they don’t sneeze then – so how does the infectiousness show up? One might hope that in practice they are much less likely to pass on the infection than they would be a day or two later, even if the virus load in their nasal secretions is just as high, for example. Can we be reassured about this? Any thoughts? Separate from the question of just what the mechanics of transmission are, have there been any studies on how likely you are to catch flu from someone who is going to develop symptoms in 12 hours as opposed to someone who developed symptoms 12 hours ago, say?

  6. #6 revere
    November 13, 2006

    Mathematician (what area? I’m partial to algebra, myself): My understanding, on the basis of very scant data, is that shedding occurs prior to symptoms but is much less. Viral particles are put into the environment by breathing and speaking. So the first few days of symptoms spread the disease more than the asymptomatic phase.

  7. #7 RobT
    November 13, 2006

    Revere, can you shed any light on the basis for the oft repeated advice to stay 3 feet away from anyone who is coughing/sneezing to “avoid the flu”? I read somewhere it harkens back to a study done in the 1930′s about how far apart hospital beds were apart to avoid cross infection. It is alarming that such old and probably irrelevant information is still being peddled by medical authorities. For example see the information video on the Australian Health Department website where the Chief Medical Officer endorses stepping back from a sneezer to avoid catching pandemic flu.
    Oh my God, we’ve got a long way to go. I hope there is enough time to get better information out to the unsuspecting public and HCW’s.

    http://www.health.gov.au/internet/wcms/publishing.nsf/Content/phd-pandemic-prepared-protected.htm

  8. #8 revere
    November 13, 2006

    RobT: This is based on the assumption of droplet spread. It’s often given as 3 to 5 feet and the idea is that droplets will fall out before ghey get that far. Even if it were droplet spread, you can see what an uncontrolled sneeze produces. So that advice isn’t very well founded — IMHO.

  9. #9 Lisa the GP
    November 13, 2006

    The UV units do seem a strange oversight. On the other hand if you believe a pandemic will take out electrical power after a few weeks, UV lights wouldn’t have power to run.

    It seems like such lights in the air systems would be a good investment for hospitals even in the absence of a pandemic. They’re used in respiratory isolation areas but wider use might be a good thing?

  10. #10 M. Randolph Kruger
    November 13, 2006

    Reverse air wash systems have been shown to be 100% effective on a two pass system. Its a deal where if you have enough pull on the system it pulls the air into tubes that are perforated on one end. The air enters the tube on one end (multiple tubes) and aereates as bubbles rising into a tub of chlorinated water. It enters a chamber where it does it again and then returns to the intake into an air handler. Problems: Chlorinated water vapor is corrosive and will eat galvanized furnace/air handler units parts up. It also creates a slight chlorine gas element in the breathing air.

    Cl gas though even in low concentrations might give some headaches but the system washes all particulants out along with Mr. Bug and leaves it as sludge in the bottom of the tank. I have no idea what it would take to actually do one, but the concentrations used are the same in pool water.

    UV lights? Better have the energizer bunny on staff. Both of these will require that you have electricity and thats a LOT of assumption right now that it will be on. Lisa if we lose even one grid for a month there are some numbers out there that are based upon the ice storm up in Ontario a couple of years ago that are pretty grim. Fuel supplies would drop to near nothing within 10 days. That would be the bell ringing for the next to the last round for a lot of people if its cold.

  11. #11 Dylan
    November 13, 2006

    I never sneeze “forward;” I always sneeze “downward.” Always. When I fail to sneeze, my eyes always water (for whatever reason); when I “successfully” sneeze, they never do. Sneezing always feels good; not sneezing never feels good.

  12. #12 Mary in Hawaii
    November 14, 2006

    Revere: Could the fact that UV from sun is more direct and intense in summer than winter have anything to do with the seasonality of the flu? And drier air leads to drier respiratory passages (at least upper passages) with more cracking, right?
    Also, the sept22 WHO influenza research report mentions that there has been a change in the virus shedding patterns in birds, where there is now increased shedding from the respiratory tract rather than cloaca. I believe your papers on influenza stated that the H5N1 receptor in birds was in their digestive tract, whereas the equivalent human receptor was in the human respiratory tract. So, based on the WHO report, a few questions: What is the receptor in the bird’s respiratory tract, how does it differ from the receptor in the bird’s digestive tract, and how is it similar/dissimilar to the receptor in the human respiratory tract? (inquiring minds and all that.)
    thanks!

  13. #13 Mathematician
    November 14, 2006

    Revere, thanks, that makes sense. Yes, I’m an algebraist by training (representation theory), although these days I work in informatics (theoretical computer science/mathematical software engingeering). That probably thoroughly compromises my anonymity :-)

  14. #14 lugon
    November 14, 2006

    We want to see how aerosol transmission can be stopped or at least minimised, for several environments. We don’t need a flu virus to study aerosols. Where are those studies?

    What would the current recomendation be? Sneeze into a bag and then throw it away? Don’t you even talk if you’ve been near anyone that was ill?

    Simple masks – do they stop a fraction of aerosols? How much of a fraction would lower the R-naught to low-enough levels? If we stop 1/2, but at 1/100th is still infectious, then we’ve gained nothing (I think).

    Humid masks – could we try turning aerosols into bigger droplets?

  15. #15 revere
    November 14, 2006

    MiH: The humidity data Tellier mentions relates to how long the virus stays viable, but you point out that it also affects the host, emphasizing once again that infection is an interaction between agent, host and environment. On the other hand, Tellier’s point is that the data suggest (epidemiologists like to use data as plural, an affectation) the site of infection is in the lower respiratory tract, not the upper as in the nose. There is still a lot that needs to be sorted out and while Tellier’s points make a lot of sense to me, they are based on scant data, especially about where the α2,3 receptors are found in humans and birds. You’d think this was all figured out, but it isn’t and the data are somewhat contradictory.

    Mathematician: Good. I like algebraists, especially group theorists. I knew the late George Mackey well and my undergraduate advisor was RH Bruck (Bruck-Ryser Theorem). I took analysis from Rudin in one of his first years, and interestingly he used Creighton Buck’s book, not his own, which is now a classic. I’m a physician but I dabble in lattice theory via Formal Concept Analysis. Glad to have mathematicians reading.

  16. #16 lugon
    November 14, 2006
  17. #17 revere
    November 14, 2006

    lugon: the humidity issue is not just about turning the aerosol into a larger particle (erodynamically speaking). The data Tellier cites relates to the rate of exponential decay in viability of the virus. For some reason enveloped viruses like flu don’t like humid environments, reason unknown. It is the reverse for uneveloped viruses, according to Tellier, although I haven’t seen the data. So humidity might still be useful for flu, although for a different reason but could have effects on other diseases. No simple fix here. I think UVGI is something that is being neglected and I’m not sure why. Some fluwikians might look at the practicality of dong this in a home sickroom. I’m sure commercial units are expensive but some hacker might think of a way to do it on the cheap. It could also be dangerous, though. Someone should look at it.

  18. #18 RobT
    November 14, 2006

    Some of us Fluwikians have been investigating UVC as a docontamination strategy and as an infection prevention strategy during SIP.

    The UVC bulbs are readily available in both florescent type and U-tube shape for water sterilisation or in air conditioning systems as are the fittings from specialty lighting retailers. It isn’t expensive at all, the florescent UVC tubes are about $20 and use the same florescent light fittings as regular florescent lights.

    The crystal U-tubes and fittings are a bit more expensive, but I think are an excellent water sterilizing option compared to filters, particularly for larger volumes of water.

    BUT, remember UVC is damaging to the eyes and absolutely requires the use of proper eyewear that blocks UVC. These are about $30 dollars or so.

  19. #19 Dizzy
    November 15, 2006

    Your picture of the sneeze reminded me of a poster that has recently appeared on a prominent billboard on a main route into Edinburgh city centre. It shows the sneeze similar to the one above and words to the effect of ‘…flu hits you at 125mph… get your flu shot’. I’ve never seen anything like this before in Scotland, makes me wonder if TPTB are a bit concerned.

    The RH in our air conditioned office is 34% when it should be between 40 and 60% (we got our own gadgets to measure this). I’d guess many offices are the same. We complain about it constantly. Maybe if we all start dropping dead they’ll finally do something about it other than tell us not to open the windows.

    Oh, and, um… the datum is, the data are. Pedantic old hack that I am.

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