title: Seasonal drivers of pneumococcal disease incidence: impact of bacterial carriage and viral activity.
abstract: BACKGROUND
  Winter-seasonal epidemics of pneumococcal disease provide an opportunity to understand the drivers of incidence. We sought to determine whether seasonality of invasive pneumococcal disease is caused by increased nasopharyngeal transmission of the bacteria or increased susceptibility to invasive infections driven by cocirculating winter respiratory viruses.
  
  
  METHODS
  We analyzed pneumococcal carriage and invasive disease data collected from children <7 years old in the Navajo/White Mountain Apache populations between 1996 and 2012. Regression models were used to quantify seasonal variations in carriage prevalence, carriage density, and disease incidence. We also fit a multivariate model to determine the contribution of carriage prevalence and RSV activity to pneumococcal disease incidence while controlling for shared seasonal factors.
  
  
  RESULTS
  The seasonal patterns of invasive pneumococcal disease epidemics varied significantly by clinical presentation: bacteremic pneumococcal pneumonia incidence peaked in late winter, whereas invasive nonpneumonia pneumococcal incidence peaked in autumn. Pneumococcal carriage prevalence and density also varied seasonally, with peak prevalence occurring in late autumn. In a multivariate model, RSV activity was associated with significant increases in bacteremic pneumonia cases (attributable percentage, 15.5%; 95% confidence interval [CI], 1.8%-26.1%) but was not associated with invasive nonpneumonia infections (8.0%; 95% CI, -4.8% to 19.3%). In contrast, seasonal variations in carriage prevalence were associated with significant increases in invasive nonpneumonia infections (31.4%; 95% CI, 8.8%-51.4%) but not with bacteremic pneumonia.
  
  
  CONCLUSIONS
  The seasonality of invasive pneumococcal pneumonia could be due to increased susceptibility to invasive infection triggered by viral pathogens, whereas seasonality of other invasive pneumococcal infections might be primarily driven by increased nasopharyngeal transmission of the bacteria.
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Weinberger
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Grant
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Steiner
authors.forename: Robert
authors.initials: R
authors.lastname: Weatherholtz
authors.forename: Mathuram
authors.initials: M
authors.lastname: Santosham
authors.forename: Cécile
authors.initials: C
authors.lastname: Viboud
authors.forename: Katherine L
authors.initials: KL
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D002353:Carrier State / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D015994:Incidence; D007223:Infant; D011008:Pneumococcal Infections / Q000453:epidemiology*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000453:epidemiology*; D012621:Seasons
keywords: RSV; co-infections; pneumococcal; pneumonia; seasonality