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    Original Investigation
    Global Health
    July 13, 2020

    Association of Influenza Activity and Environmental Conditions With the Risk of Invasive Pneumococcal Disease

    Author Affiliations
    • 1Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
    • 2Canadian Blood Services, Ottawa, Ontario, Canada
    • 3University of Alberta, Edmonton, Alberta, Canada
    • 4University of Maryland School of Medicine, Baltimore
    • 5Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
    • 6Dalhousie University, Halifax, Nova Scotia, Canada
    • 7Philadelphia Department of Public Health, Philadelphia, Pennsylvania
    • 8Warren Alpert School of Medicine of Brown University, Providence, Rhode Island
    • 9Rhode Island Hospital, Providence
    • 10Public Health Agency of Canada, Guelph, Ontario, Canada
    JAMA Netw Open. 2020;3(7):e2010167. doi:10.1001/jamanetworkopen.2020.10167
    Key Points español 中文 (chinese)

    Question  What is the association of influenza activity and environmental conditions with invasive pneumococcal disease risk in temperate countries, and are these associations generalizable?

    Findings  In this case-crossover study of 19 566 patients from Australia, Canada, and the United States, influenza activity was associated with a short-term increase in risk of invasive pneumococcal disease, while absolute humidity was associated with a short-term decrease in invasive pneumococcal disease risk. These results were generalizable across the 3 temperate countries.

    Meaning  This study’s finding that influenza was associated with increased risk of invasive pneumococcal disease has important implications for disease control policy and practice.


    Importance  Streptococcus pneumoniae is the most commonly identified cause of bacterial pneumonia, and invasive pneumococcal disease (IPD) has a high case fatality rate. The wintertime coseasonality of influenza and IPD in temperate countries has suggested that pathogen-pathogen interaction or environmental conditions may contribute to IPD risk.

    Objectives  To evaluate the short-term associations of influenza activity and environmental exposures with IPD risk in temperate countries and to examine the generalizability of such associations across multiple jurisdictions.

    Design, Setting, and Participants  This case-crossover analysis of 19 566 individuals with IPD from 1998 to 2011 combined individual-level outcomes of IPD and population-level exposures. Participants lived in 12 jurisdictions in Canada (the province of Alberta and cities of Toronto, Vancouver, and Halifax), Australia (Perth, Sydney, Adelaide, Brisbane, and Melbourne), and the United States (Baltimore, Providence, and Philadelphia). Data were analyzed in 2019.

    Exposures  Influenza activity, mean temperature, absolute humidity, and UV radiation at delays of 1 to 3 weeks before case occurrence in each jurisdiction.

    Main Outcomes and Measures  Matched odds ratios (ORs) for IPD associated with changes in exposure variables, estimated using multivariable conditional logistic regression models. Heterogeneity in effects across jurisdictions were evaluated using random-effects meta-analytic models.

    Results  This study included 19 566 patients: 9629 from Australia (mean [SD] age, 42.8 [30.8] years; 5280 [54.8%] men), 8522 from Canada (only case date reported), and 1415 from the United States (only case date reported). In adjusted models, increased influenza activity was associated with increases in IPD risk 2 weeks later (adjusted OR [aOR] per SD increase, 1.07; 95% CI, 1.01-1.13). Increased humidity was associated with decreased IPD risk 1 week later (aOR per 1 g/m3, 0.98; 95% CI, 0.96-1.00). Other associations were heterogeneous; metaregression suggested that combinations of environmental factors might represent unique local risk signatures. For example, the heterogeneity in effects of UV radiation and humidity at a 2-week lag was partially explained by variation in temperature (UV index: coefficient, 0.0261; 95% CI, 0.0078 to 0.0444; absolute humidity: coefficient, −0.0077; 95% CI, −0.0125 to −0.0030).

    Conclusions and Relevance  In this study, influenza was associated with increased IPD risk in temperate countries. This association was not explained by coseasonality or case characteristics and appears generalizable. Absolute humidity was associated with decreased IPD risk in the same jurisdictions. The generalizable nature of these associations has important implications for influenza control and advances the understanding of the seasonality of this important disease.