A cross sectional study by Stefan Flasche and coworkers document the serotype replacement of Streptococcus pneumoniae that has occurred in England since the introduction of PCV7 vaccination.
We investigated the effect of the 7-valent pneumococcal conjugate vaccine
(PCV7) programme in England on serotype-specific carriage and invasive
disease to help understand its role in serotype replacement and predict the
impact of higher valency vaccines.
Methods and Findings
Nasopharyngeal swabs were taken from children <5 y old and family members
(n = 400) 2 y after introduction
of PCV7 into routine immunization programs. Proportions carrying
Streptococcus pneumoniae and serotype distribution
among carried isolates were compared with a similar population prior to PCV7
introduction. Serotype-specific case∶carrier ratios (CCRs) were
estimated using national data on invasive disease. In vaccinated children
and their contacts vaccine-type (VT) carriage decreased, but was offset by
an increase in non-VT carriage, with no significant overall change in
carriage prevalence, odds ratio 1.06 (95% confidence interval
0.76–1.49). The lower CCRs of the replacing serotypes resulted in a
net reduction in invasive disease in children. The additional serotypes
covered by higher valency vaccines had low carriage but high disease
prevalence. Serotype 11C emerged as predominant in carriage but caused no
invasive disease whereas 8, 12F, and 22F emerged in disease but had very low
Because the additional serotypes included in PCV10/13 have high CCRs but low
carriage prevalence, vaccinating against them is likely to significantly
reduce invasive disease with less risk of serotype replacement. However, a
few serotypes with high CCRs could mitigate the benefits of higher valency
vaccines. Assessment of the effect of PCV on carriage as well as invasive
disease should be part of enhanced surveillance activities for PCVs.
Please see later in the article for the Editors' Summary
Pneumococcal diseases—major causes of illness and death in children and
adults worldwide—are caused by Streptococcus
pneumoniae, a bacterium that often colonizes the nasopharynx
(the area of the throat behind the nose). Carriage of S.
pneumoniae bacteria does not necessarily cause disease.
However, these bacteria can cause local, noninvasive diseases such as ear
infections and sinusitis and, more rarely, they can spread into the lungs,
the bloodstream, or the covering of the brain, where they cause pneumonia,
septicemia, and meningitis, respectively. Although these invasive
pneumococcal diseases (IPDs) can be successfully treated if administered
early, they can be fatal. Consequently, it is better to protect people
against IPDs through vaccination than risk infection. Vaccination primes the
immune system to recognize and attack disease-causing organisms (pathogens)
rapidly and effectively by exposing it to weakened or dead pathogens or to
pathogen molecules (antigens) that it recognizes as foreign.
Why Was This Study Done?
There are more than 90 S. pneumoniae variants or
“serotypes” characterized by different polysaccharide (complex
sugar) coats, which trigger the immune response against S.
pneumoniae and determine each serotype's propensity to
cause IPD. The pneumococcal conjugate vaccine PCV7 contains polysaccharides
(linked to a protein carrier) from the seven serotypes mainly responsible
for IPD in the US in 2000 when routine childhood PCV7 vaccination was
introduced in that country. PCV7 prevents both IPD caused by the serotypes
it contains and carriage of these serotypes, which means that, after
vaccination, previously uncommon, nonvaccine serotypes can colonize the
nasopharynx. If these serotypes have a high invasiveness potential, then
“serotype replacement” could reduce the benefits of vaccination.
In this cross-sectional study (a study that investigates the relationship
between a disease and an intervention in a population at one time point),
the researchers investigate the effect of the UK PCV7 vaccination program
(which began in 2006) on serotype-specific carriage and IPD in England to
understand the role of PCV7 in serotype replacement and to predict the
likely impact of vaccines containing additional serotypes (higher valency
What Did the Researchers Do and Find?
The researchers examined nasopharyngeal swabs taken from PCV7-vaccinated
children and their families for S. pneumoniae, determined
the serotype of any bacteria they found, and compared the proportion of
people carrying S. pneumoniae (carrier prevalence) and the
distribution of serotypes in this study population and in a similar
population that was studied in 2000/2001, before the PCV vaccination program
began. Overall, there was no statistically significant change in carrier
prevalence, but carriage of vaccine serotypes decreased in vaccinated
children and their contacts whereas carriage of nonvaccine serotypes
increased. The serotype-specific case-to-carrier ratios (CCRs; a measure of
serotype invasiveness that was estimated using national IPD data) of the
replacing serotypes were generally lower than those of the original
serotypes, which resulted in a net reduction in IPD in children. Moreover,
before PCV7 vaccination began, PCV7-included serotypes were responsible for
similar proportions of pneumococcal carriage and disease; afterwards, the
additional serotypes present in the higher valency vaccines PVC10 and PVC13
were responsible for a higher proportion of disease than carriage. Finally,
three serotypes not present in the higher valency vaccines with
outstandingly high CCRs (high invasiveness potential) are identified.
What Do These Findings Mean?
These findings document the serotype replacement of S.
pneumoniae that has occurred in England since the introduction
of PCV7 vaccination and highlight the importance of assessing the effects of
pneumococcal vaccines on carriage as well as on IPDs. Because the additional
serotypes included in PCV10 and PCV13 have high CCRs but low carriage
prevalence and because most of the potential replacement serotypes have low
CCRs, these findings suggest that the introduction of higher valency
vaccines should further reduce the occurrence of invasive disease with
limited risk of additional serotype replacement. However, the emergence of a
few serotypes that have high CCRs but are not included in PCV10 and PCV13
might mitigate the benefits of higher valency vaccines. In other words,
although the recent introduction of PCV13 into UK vaccination schedules is
likely to have an incremental benefit on the reduction of IPD compared to
PCV7, this benefit might be offset by increases in the carriage of some high
CCR serotypes. These serotypes should be considered for inclusion in future
Please access these Web sites via the online version of this summary at
The US Centers for Disease Control and Prevention provides
information for patients and health professionals on all aspects of
pneumococcal disease and pneumococcal
The US National Foundation for Infectious Diseases has a fact sheet
on pneumococcal diseases
The UK Health Protection Agency provides information on pneumococcal disease and on pneumococcal vaccines
The World Health Organization also provides information on pneumococcal vaccines
MedlinePlus has links to further information about pneumococcal infections (in English and Spanish)