Oct 19, 2007 (CIDRAP News) – Scientists investigating why seasons drive annual influenza epidemics have charted how low humidity and cold temperatures contribute to the spread of the disease in laboratory animals.

The research group, from Mt Sinai School of Medicine in New York City, published their findings yesterday in the October issue of Public Library of Science Pathogens (PLoS Pathogens).

In the two-pronged study, the researchers first tested aerosol influenza A virus transmission at different relative humidities and temperatures among guinea pigs. Then they assessed whether cold temperatures influenced the immune response of infected animals by extracting RNA from their nasal tissues for polymerase chain reaction (PCR) testing.

The researchers used guinea pigs because they learned from a medical journal that guinea pigs kept for research purposes in 1919 at a New Mexico army base died during the 1918 flu pandemic, Peter Palese, a Mt. Sinai virologist and senior author of the study, said in a report today from New Scientist, a British science and technology magazine.

"We didn't know guinea pigs got the flu. They are no longer popular lab animals, and no one had tried them," he told New Scientist.

To tease out the effects of temperature and humidity on virus spread, the group performed 20 trials at different humidities and temperatures, each involving eight animals. For each trial, four guinea pigs were intranasally inoculated with influenza A virus. Then pairs of infected and uninfected animals were housed individually in adjoining cages. Nasal wash samples were collected from the animals about every other day, and serum samples were collected before infection and on day 17 after infection.

Five different humidity levels were tested at 20°C: 20%, 35%, 50%, 65%, and 80%. The researchers found that transmission was most efficient at the two lowest humidity levels, at which three or four of the exposed guinea pigs became infected. At 50% relative humidity, only one of the four animals contracted influenza. More were infected in 65% humidity, but no disease transmission was noted at 80% humidity.

In the temperature experiments, animals were exposed to 5°C, 20°C, and 30°C at different humidity levels. The investigators found that transmission was more efficient when guinea pigs were kept at 5°C than at 20°C, and at 30°C they detected no disease spread. In addition, the duration of peak viral shedding at 5°C was 40 hours longer than at 20°C.

"Our data implicate low relative humidities produced by indoor heating and cold temperatures as features of winter that favor influenza virus spread," they concluded.

In assessing the effect of low temperatures on innate immune response, the authors found that housing animals at 5°C didn't greatly impair their immune response when compared with that of animals housed at 20°C. This finding runs counter to the conventional wisdom, the authors asserted.

Palese, quoted in a report yesterday from the LiveScience news Web site, said, "We've always thought the immune system wasn't as active during the winter, but that doesn't really seem to be the case."

The researchers said their findings on humidity effects raise several possibilities about influenza transmission mechanisms:

Breathing dry air could desiccate the nasal mucosa and reduce ciliary clearance of the virus—though the guinea pigs weren't exposed to dry air for very long before they became infected.

The virus could be more stable at low humidity.

At low humidity, water evaporates quickly from bioaerosols, leaving droplet nuclei that remain airborne and increase the opportunity for pathogen transmission.

Low temperatures could affect hosts in ways that contribute to the infection mechanism, the report says. For example, cooling the nasal mucosa is thought to increase the viscosity of the mucous lining, which could reduce ciliary clearance of the virus. Also, cooling in the nasal passages may provide a more stable environment for flu viruses.

The authors said their findings suggest that controlling indoor temperature and humidity—warmer than 68°F and 50% to 80% relative humidity—might slow influenza virus transmission.

Michael T. Osterholm, PhD, MPH, director of the University of Minnesota Center for infectious Disease Research and Policy, publisher of CIDRAP News, said the seasonality of influenza outbreaks is clearly important. However, he said other factors besides just temperature and humidity must be involved.

"Previous pandemic outbreaks were widespread in other seasons of the year," he told CIDRAP News. For example, he said, the spread of flu in August and September during the 1918 pandemic was especially dramatic.

Lowen AC, Mubareka S, Steel, et al. Influenza virus transmission is dependent on relative humidity and temperature. PLoS Pathogens 2007 Oct ;3(10):e151 [Full text]