Synergistic Effect of Ambient Ozone, Relative Humidity, and Temperature on Epidemic Patterns of Influenza: A Hypothesis and Its Verification

ABSTRACT The mechanisms underlying seasonal patterns in influenza epidemics have long been an enigma. Our laboratory study revealed that ambient ozone significantly inactivates airborne influenza viruses synergistically with higher relative humidity and temperature. This led us to hypothesize that natural seasonal fluctuations in these ambient factors enhance or mitigate the influenza‐transmission risk by altering the efficiency of airborne virus inactivation, thereby contributing to the continuation or subsiding of influenza epidemics. To test the hypothesis, we examined datasets covering 5 years of annual environmental ozone concentrations, relative humidity, and temperature, and reported influenza case numbers in two cities in Japan, Sendai and Naha, which exhibit typical temperate and subtropical climate patterns, respectively; based on the findings of our previous study and actual ambient environmental data, we estimated the influenza airborne‐transmission risk in these cities and compared it with observed epidemics. In both cities, the persistence of winter epidemics was strongly associated with low ozone concentration (< 35 ppb), and their subsiding in spring was associated with increases in ozone (≧ 35 ppb) and relative humidity (≧ 50%), even at lower temperature (< 20°C). The summer outbreak in Naha was not suppressed solely under high temperatures (25°C–30°C) and relative humidity (≧ 70%), but was associated with a subsequent increase in ozone (≧ 35 ppb). A similar phenomenon was recognized during the 2009 influenza pandemic. These results were consistent with our hypothesis: influenza epidemic patterns corresponded with the influenza transmission risk estimated from the synergistic inactivation patterns of airborne viruses by ambient ozone, relative humidity, and temperature.