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Influenza Increases Risk of Invasive Pneumococcal Disease: A Multi-Country Study

40 Pages Posted: 14 Mar 2019

See all articles by Isha Berry

Isha Berry

University of Toronto - Dalla Lana School of Public Health

Ashleigh R. Tuite

University of Toronto

Angela Salomon

University of Toronto - Dalla Lana School of Public Health

Steven Drews

Canadian Blood Service

Anthony Harris

University of Maryland - School of Medicine

Todd Hatchette

Nova Scotia Health Authority

Caroline Johnson

Philadelphia Department of Public Health

Jeff Kwong

University of Toronto - Dalla Lana School of Public Health

Jose Lojo

Philadelphia Department of Public Health

Allison McGeer

University of Toronto - Dalla Lana School of Public Health

Leonard Mermel

Brown University - Warren Alpert Medical School

Victoria Ng

Public Health Agency Canada

David Fisman

University of Toronto - Dalla Lana School of Public Health; University of Toronto, Faculty of Medicine, Department of Medicine, Division of Infectious Diseases

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Abstract

Background: Streptococcus pneumoniae is the most commonly identified cause of bacterial pneumonia, and invasive pneumococcal disease (IPD) has a high case fatality rate.  The wintertime co-seasonality of influenza and IPD in temperate countries has suggested that pathogen-pathogen interaction or environmental conditions contribute to IPD risk.  We evaluated the contribution of influenza and environmental conditions, using standardized methodology, across multiple geographical regions.    

Methods: Case data for 25,292 cases from jurisdictions in Canada, the United States and Australia were available.  Associations between influenza, temperature, absolute humidity and ultraviolet radiation and IPD were evaluated using a case-crossover design. Identical models were used in all jurisdictions; heterogeneity of effects was explored using meta-analytic methods.    

Findings: In adjusted models, elevated influenza activity at a 2-week lag was associated with increases in IPD risk (adjusted OR (aOR) per standard deviation increase 1.07, 95% CI: 1.01-1.13). Increased humidity decreased IPD risk at a 1-week lag (aOR per gram.m-3 of water 0.98, 95% CI 0.96-1.00).  Other effects were heterogeneous; meta-regression suggested that combinations of environmental factors might represent unique local "risk signatures".    

Interpretation: Influenza drives IPD risk in temperate countries.  This association is not explained by co-seasonality or case characteristics and appears generalizable.  Absolute humidity attenuates IPD risk in the same jurisdictions.  The generalizable nature of these associations has important implications for influenza control and advances the understanding of seasonality of this important disease.    

Funding Statement:  Supported by Canadian Institutes for Health Research Operating Grants (#222287 and #337516) and by the Canadian Immunization Research Network.

Declaration of Interests: The authors state: "None."

Ethics Approval Statement: Ethical approval for this study was obtained by the University of Toronto Research Ethics Board.

Keywords: Streptococcus pneumoniae; invasive pneumococcal disease; influenza; pneumonia; epidemiology; seasonality; case-crossover; Canada; Australia; United States

Suggested Citation

Berry, Isha and Tuite, Ashleigh R. and Salomon, Angela and Drews, Steven and Harris, Anthony and Hatchette, Todd and Johnson, Caroline and Kwong, Jeff and Lojo, Jose and McGeer, Allison and Mermel, Leonard and Ng, Victoria and Fisman, David, Influenza Increases Risk of Invasive Pneumococcal Disease: A Multi-Country Study (March 13, 2019). Available at SSRN: https://ssrn.com/abstract=3352009 or http://dx.doi.org/10.2139/ssrn.3352009

Isha Berry

University of Toronto - Dalla Lana School of Public Health

Toronto, Ontario
Canada

Ashleigh R. Tuite

University of Toronto

105 St George Street
Toronto, Ontario M5S 3G8
Canada

Angela Salomon

University of Toronto - Dalla Lana School of Public Health

Toronto, Ontario
Canada

Steven Drews

Canadian Blood Service

1800 Alta Vista Drive
Ottawa, Ontario K1G 4J5
Canada

Anthony Harris

University of Maryland - School of Medicine

655 West Baltimore Street
College Park, MD 20742
United States

Todd Hatchette

Nova Scotia Health Authority

Halifax
Canada

Caroline Johnson

Philadelphia Department of Public Health

Philadelphia, PA
United States

Jeff Kwong

University of Toronto - Dalla Lana School of Public Health

Toronto, Ontario
Canada

Jose Lojo

Philadelphia Department of Public Health

Philadelphia, PA
United States

Allison McGeer

University of Toronto - Dalla Lana School of Public Health

Toronto, Ontario
Canada

Leonard Mermel

Brown University - Warren Alpert Medical School

Providence, RI 02912
United States

Victoria Ng

Public Health Agency Canada

Ontario
Canada

David Fisman (Contact Author)

University of Toronto - Dalla Lana School of Public Health ( email )

Toronto, Ontario
Canada

University of Toronto, Faculty of Medicine, Department of Medicine, Division of Infectious Diseases ( email )

Canada