Influenza and the weather

It is well known that influenza hits hardest in winter--November to March in the Northern Hemisphere, and May to September in the Southern Hemisphere. In fact, the name influenza comes from the Italian word influenza, meaning "influence"--referring to the "influence of the season" (winter) in causing the illness. In the tropics, where there is little change in seasons, influenza occurs year-round (though increased incidence has been noted in rainy seasons--Viboud et al., 2006). Do the cold temperatures and lower humidities of winter cause increased transmission of the flu virus? If so, why is the current H1N1 swine flu outbreak doing so well, now that it is May, traditionally the end of flu season in the Northern Hemisphere? Or could it be that indoor crowding, lack of sunlight lowering vitamin D levels, and a more depressed immune system in winter are largely responsible, as some researchers have suggested?

Flu infections increase under cold or dry conditions
To test these hypotheses, researchers at the Mount Sinai School of Medicine in New York did a study in 2007 that looked at flu transmission among guinea pigs, which are highly susceptible to human influenza and easily transmit the virus to other guinea pigs (Lowen et al., 2007). The animals were placed in adjacent cages, so that infections could occur by airborne transmission, but not by direct contact (guinea pig lovers will be happy to know that the influenza virus-infected guinea pigs did not display detectable symptoms of disease--weight loss, fever, sneezing, and coughing--during the experiments). By carefully controlling temperature and humidity, the scientists were able to study the effects of each. They found that the animals shed much more of the virus--and over a longer period of time--at cold temperatures, which led to increased infection rates. The animals' immune system showed no signs of stress from the cold weather, arguing against the idea that cold conditions lead to increased infections by lowering the immune system. Lower humidities were also found to increase flu transmission rate, though the variation of infection rate with humidity was more complicated. The scientists built a model (Figure 1) to fit the data, and proposed that lower humidity increased infection rates through two mechanisms:

1) The stability of influenza virons in the suspended aerosol particles infected creatures cough out is dependent upon the humidity. Viruses are most stable at low RH (20%-40%), least stable at intermediate RH (50%), and stable again at high RH (60%-80%) (Schaffer et al., 1976). Thus, the virus has better staying power at the low moisture levels typical of winter.

2) At high RH (80%), exhaled respiratory droplets grow quite large as water vapor condenses around them, and these drops quickly settle to the ground under the force of gravity. Thus, even though the virus is stable at high humidities, it settles out of the atmosphere quickly, and cannot contribute to influenza virus spread.


Figure 1. A model of influenza transmission rates at 68°F (20°C) (dashed line) and 41°F (5°C) (solid line), as a function of relative humidity. Transmission efficiency is highest at low relative humidity, when influenza virions in an aerosol are relatively stable, and exhaled respiratory droplets stay small and don't settle out under the force of gravity. Transmission is diminished at intermediate humidity when virus particles are relatively unstable, but improves in parallel with influenza virus stability at higher humidities. At high humidity, evaporation from exhaled particles is limited, respiratory droplets settle out of the air, and transmission is blocked. At cold temperatures (solid line), transmission is more efficient than at warm temperatures (dashed line), but is reduced to a rate of 50% at higher humidities. Image credit: Lowen, A.C., S. Mubareka, J. Steel, and P. Palese, 2007, "Influenza Virus Transmission Is Dependent on Relative Humidity and Temperature", PLos Pathogons, October 2007.

The researchers found no guinea pig infections at 86°F (30°C), which implies that in tropical climates, people may transmit the virus by direct contact rather than by coughing and sneezing. A second study Lowen et al., 2009) confirmed this idea--at least among guinea pigs. The authors concluded, "To our knowledge, we demonstrate for the first time that cold temperatures and low relative humidity are favorable to the spread of influenza virus. Although other factors likely contribute to the periodicity of influenza epidemics, it is clear that air temperature and RH could play an important role. Influenza virus transmission indoors could potentially be curtailed by simply maintaining room air at warm temperatures (>20 °C) and either intermediate (50%) or high (80%) RHs".

Climate change and influenza
The results of this study imply that global warming may significantly reduce influenza world-wide, since a warmer climate will also be more humid. Typically, there are between three and five million cases of severe flu and up to 500,000 deaths worldwide each year. In the United States alone, an average of 41,400 deaths and 1.68 million hospitalizations are attributed to influenza each year. A warmer world should reduce these numbers, if the current research is correct. However, these gains must be balanced against the possibility that malaria will become more widespread in a warmer world, since malaria kills about one million people per year.


Figure 2. Combined flu and pneumonia deaths in the United Kingdom during the great 1918 flu pandemic showed that the flu had three distinct peaks: one in June - July (a relatively mild form of the disease), followed by an extremely deadly outbreak in October, then another during the winter of 1918 - 1919. The 1918 flu pandemic infected 1/3 of the world's population, killing 50 - 100 million people. Strangely, the October peak occurred almost world-wide, with Bombay, India and Boston, Massachusetts peaking the same week. Image credit: Jordan, E., "Epidemic influenza: a survey", Chicago: American Medical Association, 1927.

Flu pandemics show little seasonality
The current Mexican H1N1 swine flu outbreak is seemingly unusual, since it is hitting at the end of the traditional flu season, in April - May. However, when a new flu strain develops that humans have no immunity to, the new strain is less constrained by seasonality. According to Dr. Jeffery Taubenberger, the virologist who helped isolate the genetic code of the virus responsible for the great 1918 flu pandemic, "Historical records since the 16th century suggest that new influenza pandemics may appear at any time of year, not necessarily in the familiar annual winter patterns of inter-pandemic years, presumably because newly shifted influenza viruses behave differently when they find a universal or highly susceptible human population." Indeed, the 1918 flu pandemic reached its peak in September - October (Figure 2), and the most recent flu pandemic, the 1968 Hong Kong flu, began in July. It wouldn't surprise me if the current flu outbreak dies down in the Northern Hemisphere over the summer months, as the combined effects of high temperatures, higher humidities, less indoor crowding, and increased sunlight interfere with its spread. However, we need to be ready for the virus to reappear in the Fall--potentially in a mutated, more virulent form--such as occurred during the 1918 flu pandemic.

References
Lowen, A.C., S. Mubareka, J. Steel, and P. Palese, 2007, "Influenza Virus Transmission Is Dependent on Relative Humidity and Temperature", PLos Pathogons, October 2007.

Lowen, A.C., S. Mubareka, J. Steel, and P. Palese, 2009, "High Temperature (30°C) Blocks Aerosol but Not Contact Transmission of Influenza Virus", Journal of Virology, June 2008, p. 5650-5652, Vol. 82, No. 11 0022-538X/08/$08.00+0 doi:10.1128/JVI.00325-08

Schaffer, F.L., M.E. Soergel, and D.C. Straube, 1976, "Survival of airborne influenza virus: effects of propagating host, relative humidity, and composition of spray fluids", Arch Virol 51: 263-273.

Viboud, C, W.J. Alonso, and L. Simonsen, 2006, "Influenza in tropical regions", PLoS Med 3: e89 doi:10.1371/journal.pmed.0030089.

Vitamin D and influenza links:
http://www.medicalnewstoday.com/articles/51913.ph p
http://www.sciencedaily.com/releases/2008/08/0808 11195629.htm
http://www.vitamindcouncil.org/science/research/v itamin-d-and-influenza.shtml

Jeff Masters