Seasonality of invasive pneumococcal disease: Temporal relation to documented influenza and respiratory syncytial viral circulation
ABSTRACT Seasonal fluctuation in the incidence of invasive pneumococcal disease has been attributed to winter virus exposure (e.g., influenza and respiratory syncytial virus [RSV]). Evidence of a direct correlation of invasive pneumococcal disease with laboratory-confirmed virus seasons, however, is limited. Using two prospective surveillance networks, the temporal relation between invasive pneumococcal disease and isolation of circulating winter viruses was explored.
Episodes of invasive pneumococcal disease in five Tennessee counties were collected prospectively from January 1995 through June 2002. Virus seasons were defined using prospective laboratory-based surveillance. Correlation between weekly identification of invasive pneumococcal disease and laboratory isolation of RSV and influenza, as well as comparisons of the frequencies of invasive pneumococcal disease episodes during viral and nonviral seasons were determined.
A total of 4147 invasive pneumococcal disease episodes were identified. Weekly frequency of invasive pneumococcal disease correlated directly with the weekly frequency of isolation of RSV (r = 0.56, P <0.001) and influenza (r= 0.40, P <0.001). The average weekly frequency of invasive pneumococcal disease during RSV and influenza seasons was higher than during the nonviral seasons (P <0.001 for each year).
Weekly episodes of invasive pneumococcal disease correlated temporally with laboratory-confirmed weekly isolation of RSV and influenza, and the incidence of invasive pneumococcal disease was increased when these viruses were circulating in the community.
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ABSTRACT: Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if the interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding to penicillin binding protein 1a. Conclusion The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection.American Journal of Respiratory and Critical Care Medicine 06/2014; DOI:10.1164/rccm.201311-2110OC · 11.99 Impact Factor
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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.PLoS Medicine 01/2015; 12(1):e1001776. DOI:10.1371/journal.pmed.1001776 · 14.00 Impact Factor
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ABSTRACT: Background. Since animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci, we assessed this relationship with influenza and other respiratory viruses in young children. Methods. A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using RT-PCR. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of nasopharyngeal acquisition of new pneumococcal serotypes. Results. A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype compared to prior sample), 1029 non-acquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample) and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio: 2.19, 95% CI: 1.02-4.69) and parainfluenza-ARI (1.86, 95% CI: 1.15-3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus and adenovirus) were not associated with acquisition. Conclusions. Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease.Clinical Infectious Diseases 03/2014; 58(10). DOI:10.1093/cid/ciu148 · 9.42 Impact Factor