Plos: Respiratory infections—bacterial and viral infections of the lungs
and the airways (the tubes that take oxygen-rich air to the lungs)—are
major causes of illness and death in children worldwide. Pneumonia
(infection of the lungs) alone is responsible for about 15% of all child
deaths.
The leading cause of bacterial pneumonia in children is
Streptococcus pneumoniae, which is transmitted through contact with infected respiratory secretions.
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 also be prevented by vaccination
with pneumococcal conjugate vaccines such as PCV7.
The leading cause of
viral pneumonia is
respiratory syncytial virus (RSV), which is also
readily transmitted through contact with infected respiratory
secretions. Almost all children have an RSV infection before their
second birthday—RSV usually causes a mild cold-like illness. However,
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.
Why Was This Study Done?
Co-infections
with bacteria and viruses can sometimes have a synergistic effect and
lead to more severe disease than an infection with either type of
pathogen (disease-causing organism) alone. For example, influenza
infections increase the risk of invasive pneumococcal disease. But does
pneumococcal disease also interact with RSV infection? It is important
to understand the interaction between pneumococcal disease and RSV to
improve the treatment of respiratory infections in young children, but
the importance of bacterial infections following RSV infection is
currently unclear. Here, the researchers undertake a time series
analysis of US hospitalization data to investigate the association
between RSV activity and pneumococcal disease in infants. Time series
analysis uses statistical methods to analyze data collected at
successive, evenly spaced time points.
What Did the Researchers Do and Find?
For
their analysis, the researchers used data collected between 1992/1993
and 2008/2009 by the State Inpatient Databases on more than 700,000
hospitalizations for RSV and more than 16,000 hospitalizations for
pneumococcal pneumonia or septicemia among children under two years old
in 36 US states. Using a statistical technique called harmonic
regression to measure seasonal variations in disease incidence (the rate
of occurrence of new cases of a disease), the researchers show that RSV
and pneumococcal pneumonia shared a distinctive spatiotemporal pattern
over the study period. Next, using Poisson regression models (another
type of statistical analysis), they show that RSV was associated with
significant increases (increases unlikely to have happened by chance) in
the incidence of pneumococcal disease. Among children under one year
old, 20.3% of pneumococcal pneumonia cases were associated with RSV
activity; among children 1–2 years old, 10.1% of pneumococcal pneumonia
cases were associated with RSV activity. Finally, the researchers report
that following the introduction of routine vaccination in the US
against
S. pneumoniae with PCV7 in 2000, there was a significant decline in hospitalizations for RSV among children under one year old.
What Do These Findings Mean?
These
findings provide evidence for an interaction between RSV and
pneumococcal pneumonia and indicate that RSV is associated with
increases in the incidence of pneumococcal pneumonia, particularly in
young infants. Notably, the finding that RSV hospitalizations declined
after the introduction of routine pneumococcal vaccination suggests that
some RSV hospitalizations may have a joint viral–bacterial etiology
(cause), although it is possible that PCV7 vaccination reduced the
diagnosis of RSV because fewer children were hospitalized with
pneumococcal disease and subsequently tested for RSV. Because this is an
ecological study (an observational investigation that looks at risk
factors and outcomes in temporally and geographically defined
populations), these findings do not provide evidence for a causal link
between hospitalizations for RSV and pneumococcal pneumonia. The similar
spatiotemporal patterns for the two infections might reflect another
unknown factor shared by the children who were hospitalized for RSV or
pneumococcal pneumonia. Moreover, because pooled hospitalization
discharge data were used in this study, these results need to be
confirmed through analysis of individual-level, laboratory-confirmed
data. Importantly, however, these findings support the initiation of
studies to determine whether treatment for bacterial infections should
be considered for children with pneumonia even if they have tested
positive for RSV.