400 individuals were enrolled between 24 April 2008 and 9 November 2009. One
participant withdrew before being swabbed and in 17 individuals swabbing had to be
aborted early; these 18 participants were excluded from further analyses. The
demographic features of the remaining 382 participants were similar to the
participants in the 2001/2002 study, apart from the proportion of households with at
least one smoker, which was lower in the more recent study (). Of 180 children eligible for catch-up
or infant vaccination only four were unvaccinated.
Overview of numbers of participants recruited, their demographic
features, and household structures in the 2001/2002 and 2008/2009 carriage
A pneumococcus was grown from 127 of the 382 (33.2%) swabs and a serotype
determined in 123 (97%). The most prevalent serotypes were 19A (10), 23B (9),
11C (8), 15B (8), 21 (8), and 6C (8). Compared to prevaccination levels, we found a
significant reduction in carriage of VTs 6B, 14, 19F, 23F, and 6A. For the remaining
PCV7 types no carriage episodes of serotypes 4 and 9V were found postvaccination,
but prevaccination levels were too low to detect any significant change. VT 18C was
identified in three out of 382 (0.79%) swabs in 2008/2009 and in 25 out of
3,868 (0.64%) in the 2001/2002 study. NVTs 33F, 7F, 10A, 34, 15B, 31, 21, 3,
19A, 15C, and 23A significantly increased (p<0.05) in carriage
with odds of 40.9, 30.8, 20.4, 20.3, 16.5, 10.2, 8.2, 6.2, 4.5, 3.6, and 3.6,
respectively. A significant increase was also found in serotypes 23B, 11C, 11B, 24F,
and 33A, which were only detected in the postvaccination study.
The proportion of swabs with VT and NVT serotypes according to age group in both
studies is shown in .
The odds ratio of VT and NVT carriage postvaccination compared to prevaccination
using the GEE with binary outcome was estimated to be 0.07 95% CI
(0.03–0.16) and 4.40 95% CI (3.06–6.33), respectively, with, no
significant effect on overall carriage: 1.06 95% CI (0.76–1.49) (). When applying the same
models to individuals younger than 5 y only, we found similar patterns. In
individuals aged 5 y or older, we detected evidence for herd immunity and full
serotype replacement as well (odds ratio [OR] 0.31 95% CI
(0.04–2.49), 5.16 95% CI (1.95–13.66), respectively), although
the reduction in VT carriage was not significant.
Number of positive VT, NVT, and All (including nontypeable) carriage
isolates in 2008/2009.
Odds ratios for comparing 2001/2002 to 2008/2009 carriage using
Simpson's index of diversity for the 2001/2002 samples was 0.908 95% CI
(0.899–0.917); children: 0.891 95% CI (0.878–0.904) and adults:
0.936 95% CI (0.926–0.947). It increased significantly in the 2008/2009
samples to: 0.961 95% CI (0.953–0.969); children: 0.960 95% CI
(0.949–0.971) and adults: 0.955 95% CI (0.928–0.982).
Furthermore, the ranked frequency distribution of the serotypes, while similar in
the prevaccination era in both children and adults in our study compared to children
in Massachusetts, changed to become more distinct after vaccination ().
Top: Comparison in ranked-serotype distribution prior to vaccination in
children in Massachusetts to our findings in children (left) and adults
Prior to its introduction, PCV7 included types responsible for similar proportions of
carriage episodes (62.2%) and disease (55.9%). In 2008/2009 the
additional types covered by higher valency vaccines were more prevalent in IPD than
carriage, particularly the additional three in PCV10, which comprised 32.6%
of IPD but only 4.7% of carried isolates ().
Carriage prevalence and IPD incidence in participants less than 60 y
caused by serotypes included in PCV7, in PCV10 and not in PCV7, in PCV13 and
not in PCV10, and the remaining serotypes.
The ranking of carried serotypes by frequency of detection in the post-PCV7 dataset
and their associated CCRs as estimated from our 2008/2009 carriage prevalence data
are shown in . CCR
estimates were highly correlated (p
0.72) to those from Sleeman and colleagues estimated
from carriage incidence 
and allow to distinguish the more from the less invasive
serotypes. From the 15 most prevalent serotypes in carriage in 2008/2009 19A, 3, 7F,
and 22F stand out with a generally higher CCR. Despite their high incidence in
invasive disease serotypes 1, 8, 12F, 4, and 14 (1.14, 0.58, 0.25, 0.22, 0.14 cases
per 100,000 population, respectively, in under 60 y olds in 2008/2009) were not
detected in carriage. On the other hand, despite being found in 2008/2009 carriage
serotypes, 11C, 16A, 17A, 28F, and 33A were not found in 2008/2009 IPD at all and
only caused 0, 1, 0, 1, and 0 cases, respectively, of invasive disease out of over
13,000 isolates serotyped between July 2006 and June 2009.
Figure 2 Age-stratified serotype distribution in carriage in 2008/2009 (below,
S2) and CCR estimated from 2008/2009 carriage and IPD data
(above, Table S1).