Abstract
The importance of bacterial infections following respiratory syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were associated with changes in the rate of hospitalizations coded as RSV. We used data from the State Inpatient Databases (Agency for Healthcare Research and Quality), including >700,000 RSV hospitalizations and >16,000 pneumococcal pneumonia hospitalizations in 36 states (1992/1993-2008/2009). Harmonic regression was used to estimate the timing of the average seasonal peak of RSV, pneumococcal pneumonia, and pneumococcal septicemia. We then estimated the association between the incidence of pneumococcal disease in children and the activity of RSV and influenza (where there is a well-established association) using Poisson regression models that controlled for shared seasonal variations. Finally, we estimated changes in the rate of hospitalizations coded as RSV following the introduction of PCV7. RSV and pneumococcal pneumonia shared a distinctive spatiotemporal pattern (correlation of peak timing: ρ = 0.70, 95% CI: 0.45, 0.84). RSV was associated with a significant increase in the incidence of pneumococcal pneumonia in children aged <1 y (attributable percent [AP]: 20.3%, 95% CI: 17.4%, 25.1%) and among children aged 1-2 y (AP: 10.1%, 95% CI: 7.6%, 13.9%). Influenza was also associated with an increase in pneumococcal pneumonia among children aged 1-2 y (AP: 3.2%, 95% CI: 1.7%, 4.7%). Finally, we observed a significant decline in RSV-coded hospitalizations in children aged <1 y following PCV7 introduction (-18.0%, 95% CI: -22.6%, -13.1%, for 2004/2005-2008/2009 versus 1997/1998-1999/2000). This study used aggregated hospitalization data, and studies with individual-level, laboratory-confirmed data could help to confirm these findings. These analyses provide evidence for an interaction between RSV and pneumococcal pneumonia. Future work should evaluate whether treatment for secondary bacterial infections could be considered for pneumonia cases even if a child tests positive for RSV. Please see later in the article for the Editors' Summary.
Highlights
Respiratory infections caused by viruses and bacteria account for a substantial burden of disease in children throughout the world
Future work should evaluate whether treatment for secondary bacterial infections could be considered for pneumonia cases even if a child tests positive for respiratory syncytial virus (RSV)
There is some evidence that pneumococcus interacts with respiratory syncytial virus (RSV), which causes a large proportion of respiratory infections in young children [9]
Summary
Respiratory infections caused by viruses and bacteria account for a substantial burden of disease in children throughout the world. Sequential infections of mice with RSV and pneumococcus demonstrate that the primary viral infection decreases bacterial clearance from the lung [14] and increases bacterial virulence [15] These observations of an association between pneumococcus and RSV seemingly contradict clinical findings that bacteremia rarely occurs in children hospitalized with RSV [16], as well as a recent study from England and Wales that found no association between RSV and invasive pneumococcal disease in children aged ,5 y [17]. S. pneumoniae usually causes noninvasive diseases such as bronchitis, but sometimes the bacteria invade the lungs, the bloodstream, or the covering of the brain, where they cause pneumonia, septicemia, or meningitis, respectively These potentially fatal invasive pneumococcal diseases can be treated with antibiotics but can be prevented by vaccination with pneumococcal conjugate vaccines such as PCV7. The leading cause of viral pneumonia is respiratory syncytial virus (RSV), which is readily transmitted through contact with infected respiratory secretions. Some children infected with RSV develop pneumonia and have to be admitted to hospital for supportive care such as the provision of supplemental oxygen; there is no specific treatment for RSV infection
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