One of the enduring scientific mysteries about influenza is what causes its marked seasonal pattern. A new paper in the Journal of Virology provides a useful mini-review of the many theories. [PubMed says its free online, but it seems to be behind a subscription firewall; maybe that will change. Here’s the cite: Lofgren E, Fefferman NH, Naumov YN, Gorski J, Naumova EN., “Influenza seasonality: underlying causes and modeling theories”, J Virol. 2007 Jun;81(11):5429-36. I have a print copy only.] The most surprising thing to most people who don’t follow this is that this is still a mystery. We’ve known that there is a predictable “flu season” for a very long time. We just don’t know why. The new paper confirms this and remarks on how often seasonality is taken as a given, not as something to be explained. Over the years many explanations have been advanced, hypothesized or speculated, although few have been tested epidemiologically.
A number concentrate on the host, that is, us. Maybe our resistance or susceptibility to influenza virus varies seasonally. Among the possibilities are seasonal variations in immune function, perhaps mediated by sunlight (or its lack), diet or differences in behavior and hence frequency and intimacy of person to person contact. Crowding, air travel, the school year and other seasonal differences in behavior are frequently invoked, especially in the lay press, but as some have pointed out, large international conventions in the summer or other occasions that produce crowding don’t seem to induce outbreaks “out of season.”
Maybe the season affects the virus. The most frequent factors mentioned are temperature and humidity, both known to affect the survivability of the virus. One possibility not mentioned by Lofgren et al. is that the lower humidity in the fall increases the proportion of aerosolized material with infective virus that is of small aerodynamic diameter. But I speculate (like everyone else). Included in their catalog of suggested causes are effects of indoor heating systems, air travel and a variety of other things. One of the more bizarre ideas they report from the literature (a paper in 1989) is that the virus exists as a huge aerosol cloud in cities in China and the viral miasma is carried by upper level wind currents to Europe and transoceanically to North America. They are politely skeptical of the idea. I’ll be less polite: dumb.
Finally, Lofgren et al. mention the possibility that the periodic nature is an inherent property of disease dynamics. I know two of the five authors and they are both mathematical modelers, and good ones, too. So I was especially interested to hear what they had to say. They divide the models into two piles, those that produce periodic patterns by some external driver (e.g., letting R0 to vary periodically) and those where the periodic pattern emerges from the operation of the system, much as a weight on a spring will oscillate up and down without any external force. The former is just a mathematical description of the unknown factor in the world that causes the seasonality, but the latter is quite different. It says, in effect, that seasonality might be produced without any “ouatsie” factor in the world, like temperature or host variation, causing it. We know that systems that have different strains interacting can do this, and two of the authors, Fefferman and Naumova show previously unpublished data that fairly small differences in social interactions between groups of people in the community (e.g., between the elderly and children) can produce startlingly different patterns, some showing periodic behavior and others showing none.
The authors conclude, naturally but somewhat unhelpfully, that the actual situation is complex and seasonality likely results from many different factors. That kind of conclusion is always a safe bet, but I am still hopeful the answer will be simpler. My interest in mathematical modeling makes me sympathetic to the emergent behavior idea, but if I had to guess (and I do have to guess), I’d say it was a combination of inherent disease dynamics (the emergent idea) combined with a simple external phase resetter from the environment. This is like what happens with our body’s inherent circadian rhythm, which operates on a cycle longer than 24 hours, but gets “reset” by the day light cycle. We are still trying to puzzle out how that resetting occurs for circadian rhythm, but the goal is to figure out the mechanism so we can do something about sleep disorders and other derangements of the cycle. If we can do the same for flu — that is, identify the mechanisms — we might also be able to damp out the huge increase in disease incidence each winter.
Why there is a flu season: just one more thing you thought we knew but don’t.