VACCINE REPORTS

Impact of 13-valent Pneumococcal Conjugate Vaccine on

Pneumococcal Nasopharyngeal Carriage in Children With Acute
Otitis Media
Robert Cohen, MD,* Corinne Levy, MD,* Edouard Bingen, PhD, Marc Koskas, MD,*
Isabelle Nave, MD, and Emmanuelle Varon, MD

Agency and the US Food and Drug Administration have granted a

Background: 13-valent pneumococcal conjugate vaccine (PCV13) licen-
market authorization to new PCVs purely on the immune response
sure was based on the immune response (enzyme-linked immunosorbent
(enzyme-linked immunosorbent assay [ELISA] and opsonophago-
assay and opsonophagocytic assay) compared with PCV7. National sur-
cytic assay [OPA]) compared with PCV7 (serotypes 4, 6B, 9V, 14,
veillance program of pneumococcal nasopharyngeal (PNP) carriage in
18C, 19F, and 23F). Because there are limitations to the ability of
children with acute otitis media (AOM) was set up in 2001 when PCV7
immunogenicity data to predict protective efficacy conferred by
was introduced in France and continues to the present. This program was
these new PCVs, postmarketing surveillance and/or effectiveness
used in 2010 2011 to assess the effect of the implementation of PCV13 on
studies are critical, particularly for the added serotypes.2 The
PNP carriage in young children with AOM.
nasopharynx acts as the primary reservoir from which pneumo-
Methods: Between October 2010 and March 2011, 58 pediatricians ob-
coccus is spread within the community and represents the site
tained 943 nasopharyngeal swabs from children (6 to 24 months of age)
where the selective pressure exhibited by antibiotics or vaccines
with AOM. The swabs were sent for analysis to the French National
occurs.3 In addition to surveillance of invasive pneumococcal
Reference Centre for Pneumococci. Demographics, medical history, and
disease (IPD), monitoring the changes in pneumococcal nasopha-
physical examination findings were recorded.
ryngeal (PNP) colonization is important because it may provide
Results: Among 943 children enrolled (mean age, 13.4 months), 651 had
early information relevant to vaccine effectiveness. It is reasonable
received at least 1 dose of PCV13 and 285 received PCV7 only. Among
to believe that prevention of new acquisition of a given serotype
PCV13-vaccinated children, overall PNP carriage and carriage of serotypes
will be associated with clinical protection against noninvasive and,
not in PCV7 were significantly lower as compared with children exclusively
consequently, invasive disease.4 Furthermore, it is important to
vaccinated with PCV7 (53.9% vs. 64.6%, P 0.002 and 9.5% vs. 20.7%, P
document any effects on carriage because they are the basis of
0.0001, respectively). For serotypes 19A, 7F, and 6C, the carriage rates
indirect (herd) protection. To determine whether the use of PCV7
were also significantly lower in PCV13-vaccinated patients than in patients
caused any shift in the Streptococcus pneumoniae serotype distri-
only vaccinated by PCV7: 7.5% versus 15.4%, P 0.001, 0.5% versus 2.8%,
bution from nasopharyngeal samples of children with acute otitis
P 0.002, and 3.7% versus 8.4%, P 0.003, respectively.
media (AOM), a national epidemiologic study was initiated in
Conclusion: In young children (2 years) with AOM, this study suggests
France in 2001 (when PCV7 was introduced) and continues
that PCV13 has an impact on overall PNP carriage, as well as on serotypes
currently.5 This study was requested by the European Medicines
19A, 7F, and 6C.
Agency as a postlicensing commitment originally for PCV7 that
Key Words: pneumococcal nasopharyngeal carriage, children, 13-valent was extended for PCV13 (PCV7 serotypes 1, 3, 5, 6A, 7F, 19A).
pneumococcal conjugate vaccine Each year, during the fall and the winter, more than 700 infants
and toddlers 6 to 24 months of age who have AOM are enrolled in
(Pediatr Infect Dis J 2012;31: 297301) a prospective PNP carriage surveillance study. In 2010, French
authorities recommended routine infant immunization with PCV13
at 2, 4, and 12 months to replace PCV7. During the transition
period, switching from PCV7 to PCV13 was recommended at any
P lacebo-controlled trials to evaluate the protection conferred by
new pneumococcal conjugate vaccines (PCVs) with extended
serotype coverage face ethical challenges. Therefore, WHO has
point in the schedule to complete the immunization series. In
addition, a catch-up dose of PCV13 was recommended for all
children 1 to 2 years of age who had been completely vaccinated
recommended the use of immunologic correlates of protection as
previously with PCV7.6 In France, PCV13 was progressively
the basis of evaluation of new PCVs.1 The European Medicines
introduced during a period of 3 months, between early June and
early September 2010. Therefore, many of the children 6 months to 2
Accepted for publication December 22, 2011. years of age with AOM enrolled in the 2010 2011 nasopharyngeal
From the *ACTIV (Association Clinique et Therapeutique Infantile du Val de carriage study year had been immunized with PCV13. This situation
Marne), Paris, France; Departement de Microbiologie, Centre Hospitalier
Intercommunal de Creteil, Creteil, France; Service de Microbiologie, provides a unique opportunity to evaluate the impact of PCV13 on
Hopital Robert-Debre (AP-HP), Universite Denis-Diderot Paris 7, Paris, PNP carriage by comparing the pneumococcal carriage in children
France; AFPA (Association Francaise de Pediatrie Ambulatoire), Selestat, vaccinated by PCV13 with those vaccinated with PCV7 only.
France; and HEGP (Hopital Europeen Georges Pompidou), (AP-HP)
Centre National de Reference des Pneumocoques, Universite Paris 5, Paris,
France.
Supported by Pfizer Pharmaceuticals France. The authors have no other funding PATIENTS AND METHODS
or conflicts of interest to disclose.
Address for correspondence: Robert Cohen, MD, ACTIV, 27 rue Inkermann, Study Design
F94100 Saint Maur des Fosses, France. E-mail: robert.cohen@wanadoo.fr, Between October 2010 and May 2011, 58 pediatricians
activ@wanadoo.fr.
Copyright 2012 by Lippincott Williams & Wilkins
distributed throughout France took part in this prospective study.
ISSN: 0891-3668/12/3103-0297 Children of either sex, 6 months to 24 months of age, with AOM
DOI: 10.1097/INF.0b013e318247ef84 were enrolled. Diagnostic criteria for AOM included the Paradise

The Pediatric Infectious Disease Journal Volume 31, Number 3, March 2012 www.pidj.com | 297
Cohen et al The Pediatric Infectious Disease Journal Volume 31, Number 3, March 2012
algorithm for acute suppurative otitis media (effusion plus marked
redness or marked bulging or moderate redness and bulging)
associated with fever and/or otalgia and/or irritability and/or con-
junctivitis.7 Exclusion criteria were as follows: antibiotic treatment
within 7 days before enrollment, severe underlying disease, or
previous inclusion in the study during the last 12 months. Once
written informed consent was obtained, we queried the parents or
guardians regarding the childs demographic information, risk
factors for carriage of resistant bacteria (including use of antibi-
otics and day care attendance modalities), and immunization his-
tory. All data about vaccination schedule were taken from the
immunization chart (health records book) of each child and
checked in the investigators medical dossier for each patient. The
study was approved by the Saint Germain en Laye Hospital Ethics
Committee.
In the prevaccine era, our research group conducted several
studies on the nasopharyngeal flora of young children (6 to 30
months) with AOM.8 These studies showed that the carriage of S.
pneumoniae in this population exceeded 50%, and that serogroups
covered by PCV7 accounted for more than 80% of the strains.
Despite year-to-year fluctuations, none of the nonvaccine sero-
types, except 19A and 6A, were carried by more than 5% of
children or accounted for more than 10% of pneumococcal iso-
lates. Therefore, any nonvaccine serotype (excluding 6A and 19A)
isolated in more than 5% of children was defined as emergent. For
a period of 5 years, a sample size of 1825 patients carrying S.
pneumoniae was required to confer an acceptable precision of the
estimate of the carriage rate for a given serotype defined as
emergent, that is, approximately 5% 1%. Because this study
lasted several years, it was therefore necessary to enroll an average
of 365 carrier patients per year. Assuming that the rate of pneu-
mococcal carriage among children with AOM was 50%, it was
necessary to enroll a total of 730 patients per year.
Microbiologic Investigations
On inclusion, deep nasopharyngeal samples were taken
transnasally with a flexible, sterile, soft rayon swab tip. After
sampling, swabs were immediately inoculated in transport medium
(Copan Venturi Transystem, Brescia, Italy), stored at room tem-
perature, and sent within 48 hours to the National Reference
Center for Pneumococci at G. Pompidou European Hospital and to
Robert Debre Hospital, in Paris. Each swab was swirled in 200 L
of brain-heart infusion, and 20 L were smeared onto Columbia
blood agar supplemented with colistin and nalidixic acid. Bacterial
isolates were identified based on colony morphology and Gram
staining. S. pneumoniae serotyping and antibiotic susceptibility
testing were performed at the National Reference Center for
Pneumococci. Serotyping was performed using latex particles
coated with a complete panel of antisera and factor sera (Statens
Serum Institut, Copenhagen, Denmark), which enable us to iden-
tify the 91 known serotypes.5,9,10 Pneumococcal strains of known
serotypes from the Statens Serum Institute and from the French
National Reference Center for Pneumococci were used as internal
controls. Susceptibility of S. pneumoniae isolates to penicillin G
was determined from minimal inhibitory concentrations (MICs) by
the agar dilution method. Isolates were classified as penicillin
susceptible (MIC 0.06 g/mL), intermediate-resistant (0.12
MIC 1.0 g/mL), penicillin nonsusceptible (PNSP) (MIC 0.12
g/mL), or resistant (MIC 2 g/mL), according to the Clinical
and Laboratory Standards Institute.11
Statistical Analyses
Data were double entered using 4D software (version 6.4)
and analyzed using Stata SE 9.1 (Stata Corp., College Station, TX)
for univariate analysis and multivariate logistic regression (odds
298 | www.pidj.com
ratios and 95% confidence intervals). Analyses of pneumococcal
carriage (ie, overall carriage or carriage by serotype) are based on
the denominator of all children evaluated, rather than only on those
carrying S. pneumoniae because pneumococcal vaccination might
influence the carriage rate and the serotype distribution in the
population. To assess the effect of PCV13 vaccine, we defined 2
groups of patients. The first one, children as adequately PCV13
vaccinated for the age if they had received 2 doses before 12
months or at least 1 dose after this age and the second one, children
as partially PCV13 vaccinated if they had received 1 dose of
PCV13 according to the French guidelines. The cohort of children
vaccinated only with PCV7 served as the reference group. The
analyses were conducted in 3 populations: the first one compared
the reference group versus the group of children PCV13 vacci-
nated; the second one compared the reference group versus chil-
dren received a partial immunization series with PCV13; and the
last one compared the reference group versus children adequately
immunized with PCV13 for the age. The 2 test and logistic
regression were used in univariate analysis to identify potential
factors (P 0.25) for overall carriage and carriage of serotypes
19A, 6C, and 7F. Variables identified by univariate analysis were
age, PCV7 and/or PCV13 vaccination status, existence of siblings,
daycare attendance modalities, recent antibiotic treatment (within
3 months before enrollment), fever, and conjunctivitis. They were
introduced into multivariate logistic regression models.
RESULTS
Between October 2010 and May 2011, 943 infants and
toddlers (mean age SD, 13.4 5.0 months) were enrolled; 7
children (0.7%) had not received PCV and 936 (99.3%) were
immunized with PCV7 and/or PCV13. Among the vaccinated
children, 285 (30.4%) were vaccinated with PCV7 only, and 651
(69.6%) had received at least 1 dose of PCV13. In this last cohort
of PCV13 vaccinated children, 486 (74.7%) were adequately
immunized with PCV13 for the age, and 165 (25.3%) had received
a partial PCV13 immunization series. PCV vaccination status
according to age and classification used for PCV13 vaccination
status (partially or adequately) is summarized in Figure 1. The
demographic characteristics, histories, signs, and symptoms of
patients enrolled are described in Table 1. Except for age, patients
demographic characteristics (sex, day care attendance modalities,
siblings, use of antibiotics 3 months before enrollment, and history
of AOM) were similar across the groups. The percentage of
patients with conjunctivitis differed between groups. Table 2
compares pneumococcal carriage, serotypes distribution as well as
penicillin susceptibility by vaccination status. Overall pneumococ-
cal carriage, that of the additional serotypes in PCV13 (in partic-
ular serotypes 19A and 7F) and that of serotype 6C, was signifi-
cantly reduced among PCV13-vaccinated patients as compared
with children exclusively vaccinated with PCV7. The proportion
of patients carrying non-PCV13 vaccine serotypes (excluding 6C)
did not change significantly according to vaccination status. Con-
sistent with the univariate analysis, the results of the multivariate
logistic regression analysis also show that the odds ratio of carry-
ing a serotype in PCV13 but not in PCV7 ( the serotype 6C) was
significantly reduced in those who received one or more doses of
PCV13 and was unaffected by age, siblings, day care attendance,
recent antibiotics, the presence of fever, or conjunctivitis (results
not shown).
DISCUSSION
As a result of the transition from PCV7 to PCV13 in the
French national vaccination program, the 2010 2011 year of the
study allowed us to investigate pneumococcal carriage in patients
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The Pediatric Infectious Disease Journal Volume 31, Number 3, March 2012
FIGURE 1. PCV vaccination status according to age and classification used for PCV13 vaccination status (partially or
adequately).
who had been vaccinated with PCV13 during the same time
period. Although this study is not a randomized controlled trial,
patients assigned to the different analysis groups were comparable
demographically, bacteriologic analysis was conducted in labora-
tories that were blinded, and the end point is robust. Moreover, the
observed results are consistent enough to substantiate impact of
PCV13 on pneumococcal carriage. In fact, among children who
received 1 dose or more of PCV13, the impact is clear. The rates
of carriage overall, that of the 6 additional serotypes taken to-
gether, that of serotypes 19A, 7F, and 6C, as well as that of isolates
with reduced susceptibility to penicillin were significantly reduced.
After introduction of PCV7 vaccination in France, we ob-
served a slight reduction in the overall pneumococcal carriage
(20%), a marked decrease in vaccine serotypes (45%), and a
reduction in the carriage of PNSP strains (20%) in children with
AOM.5,12 In this first year after the introduction of PCV13,
vaccination with at least 1 dose of PCV13 likewise reduced the
overall pneumococcal carriage by 16.5% (64.6% vs. 53.9%), 6
additional serotype carriage by 49.2% (20.7% vs. 10.5%), and
PNSP carriage by 26.5% (29.8% vs. 21.9%).
In France as in many other countries where a national
immunization program with PCV7 was implemented, serotype
19A subsequently became the serotype most often identified in
invasive isolates from young children, in specimen from middle
ear fluid and from nasopharyngeal swabs.1317 In addition, an
important degree of antibiotic resistance is associated with sero-
type 19A.18 The dramatic decrease of the 19A carriage observed in
2012 Lippincott Williams & Wilkins
Impact of PCV13
this study, 15.4% (PCV7 vaccinated) versus 7.5% (PCV13 vacci-
nated), could be associated with a decline in disease due to this
serotype and further reduction in the prevalence of pneumococcal
strains that are PNSP.
Like serotype 19A, serotype 7F also plays a major role in
IPD after PCV7 implementation.14 With the reduction of carriage
observed in our results, we could also expect a reduction of
systemic infections caused by this serotype.
We found no significant effect on serotype 3 carriage.
Although the carriage rate of this serotype seems slightly lower in
PCV13 vaccinated children, the number of children carrying se-
rotype 3 in the PCV7-vaccinated group of patients was too small
to assess the effect of PCV13 on this serotype. The low carriage
rate of serotype 6A across all study groups of this population
attests to the effect of PCV7. Of note, our findings indicate that
PCV13 will likely provide some protection against disease caused
by serotype 6C. The observed reduction in carriage rate (8.4% vs.
3.7%) concurs with the serologic data from immunized infants
supporting that the 6A conjugate in PCV13 induces a strong
opsonophagocytic response to serotype 6C.19
We did not observe in this study a significant increase of
nonvaccine PCV13 serotypes, only serotypes 15A and 11A
reached 5% of patients enrolled.
PCV-induced immune response protects against pneumo-
coccal disease through opsonophagocytic activity (ie, serotype-
specific antibody to the capsular polysaccharide, in association
with complement). During the PCV13 clinical development, im-
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Cohen et al The Pediatric Infectious Disease Journal Volume 31, Number 3, March 2012

TABLE 1. Nasopharyngeal Carriage, Serotypes Distribution, and Penicillin Resistance According to Vaccination
Status

PCV13 Recipients
PCV7 Vaccinated Only
(Non PCV13 Vaccinated) Adequately PCV13 Partially PCV13 PCV13 Vaccinated
n (%) [95% CI] Vaccinated Vaccinated (1 Dose)
P* P P
n 285 n (%) [95% CI] n (%) [95% CI] n (%) [95% CI]
n 486 n 165 n 651

Streptococcus pneumoniae 184 (64.6) [59.0 70.1] 266 (54.9) [50.559.4] 0.008 84 (50.9) [43.258.6] 0.004 351 (53.9) [50.157.8] 0.002
PCV7 serotypes 4 (1.4) [0.32.8] 12 (2.5) [1.13.9] 0.3 3 (1.8) [0 3.9] 0.7 15 (2.3) [1.13.5] 0.4
6 additional serotypes 59 (20.7) [16.0 25.4] 48 (9.9) [7.4 12.8] 0.001 14 (8.5) [4.212.8] 0.001 62 (9.5) [7.311.8] 0.001
in PCV13
19A 44 (15.4) [11.219.7] 39 (8.2) [5.8 10.7] 0.001 10 (6.1) [2.4 9.7] 0.003 49 (7.5) [5.59.6] 0.001
7F 8 (2.8) [0.9 4.7] 2 (0.4) [0 1.0] 0.005 1 (0.6) [0 1.8] 0.1 3 (0.5) [0 1.0] 0.002
6A 0 2 (0.4) [0 1.0] 0.3 1 (0.6) [0 1.8] 0.2 3 (0.5) [0 1.0] 0.3
3 7 (2.5) [0.6 4.3] 5 (1.0) [0.11.9] 0.1 2 (1.2) [0 2.9] 0.4 7 (1.1) [0.31.9] 0.1
1 0 0 0 0
5 0 0 0 0
6C 24 (8.4) [5.211.7] 17 (3.5) [1.9 5.1] 0.003 7 (4.2) [1.17.4] 0.009 24 (3.7) [2.25.1] 0.003
Non-PCV13 serotypes 97 (34.0) [28.8 39.7] 189 (38.9) [34.7 43.3] 0.1 60 (36.4) [29.4 43.9] 0.4 250 (38.4) [34.7 42.2] 0.1
(excluding 6C)
Predominant non-PCV13
serotypes
35B 12 (4.2) [1.9 6.6] 24 (4.9) [3.0 6.9] 0.6 3 (1.8) [0 3.9] 0.2 27 (4.2) [2.6 5.7] 0.08
15A 12 (4.2) [1.9 6.6] 30 (6.2) [4.0 8.3] 0.2 5 (3.0) [0.4 5.7] 0.5 35 (5.5) [3.8 7.3] 0.4
15B/C 13 (4.6) [2.17.0] 24 (4.9) [3.0 6.9] 0.8 6 (3.6) [0.8 6.5] 0.6 30 (4.6) [3.0 6.2] 0.9
11A 11 (3.9) [1.6 6.1] 22 (4.5) [2.7 6.4] 0.7 4 (2.4) [0.5 4.8] 0.4 26 (4.0) [2.55.5] 0.9
Penicillin nonsusceptible
Intermediate 79 (27.7) [22.532.9] 103 (21.2) [17.524.8] 0.04 28 (17.0) [11.222.8] 0.01 131 (20.1) [17.0 23.2] 0.01
Resistant 6 (2.1) [0.4 3.8] 8 (1.7) [0.52.8] 0.6 4 (2.4) [0.5 4.8] 0.8 12 (1.8) [0.8 2.9] 0.8
*P compares PCV7 vaccinated only versus adequately PCV13 vaccinated.

P compares PCV7 vaccinated only versus partially PCV13 vaccinated.

P compares PCV7 vaccinated only versus PCV13 vaccinated.

Carried by more than 3% of infants.

TABLE 2. Demographic Characteristics According to Vaccination Status

PCV13 Recipients
PCV7 Vaccinated Only
(Non-PCV13 Vaccinated) Adequately PCV13 Partially PCV13 PCV13 Vaccinated
Vaccinated Vaccinated (1 Dose)

No. infants enrolled 285 486 165 651

Mean age SD (mo) 14.4 5.0* 13.8 5.3 10.5 3.0 13.0 5.0*
12 mo 55.4 (49.6 61.2) 63.6 (59.3 67.9) 26.1 (19.332.8) 54.2, (50.4 58.1)
Male 52.6 (46.8 58.5) 53.5 (49.0 57.9) 44.2 (36.6 51.9) 51.2 (47.355.0)
Type of care
Day care centre 47.7 (41.9 53.6) 46.5 (42.151.0) 45.5 (37.8 53.1) 46.4 (42.550.2)
Childminder 28.8 (23.534.1) 32.5 (28.336.7) 29.7 (22.736.7) 31.8 (28.235.4)
Home 23.5 (18.6 28.5) 21.0 (17.4 24.6) 24.8 (18.231.5) 21.8 (18.6 25.0)
Siblings 56.1 (50.3 61.9) 54.7 (50.359.2) 58.8 (51.2 66.4) 55.6 (51.8 59.4)
Use of antibiotics 3 mo 44.0 (38.2 49.8) 45.1 (40.6 49.5) 45.5 (37.8 53.1) 45.2 (41.3 49.0)
before enrolment
Conjunctivitis 23.9 (18.9 28.8) 30.5 (26.334.6) 32.1 (24.9 39.3) 30.9 (27.334.4)
Otalgia 75.8 (70.8 80.8) 74.5 (70.6 78.4) 73.9 (67.2 80.7) 74.3 (71.0 77.7)
Fever 38.5C 58.3 (52.5 64.1) 54.2 (49.8 58.7) 61.0 (53.4 68.5) 55.9 (52.0 59.7)
History of AOM 57.5 (51.8 63.3) 60.5 (56.1 64.9) 49.1 (41.4 56.8) 57.8 (54.0 61.6)
Otitis-prone children 16.5 (12.220.8) 20.0 (16.4 23.5) 14.6 (9.120.0) 18.7 (15.721.7)
Values are given as % (95% CI) unless otherwise indicated.
*P 0.0001, P compares PCV7 vaccinated only versus PCV13 vaccinated.

P 0.0001, P compares PCV7 vaccinated only versus partially PCV13 vaccinated.

P 0.02, P compares PCV7 vaccinated only versus adequately PCV13 vaccinated.

P 0.03, P compares PCV7 vaccinated only versus PCV13 vaccinated.

mune responses were evaluated in opsonophagocytic activity as-
says, considered as appropriate in vitro assays to measure the
potential vaccine-induced protective capacity.
Recently, Miller et al showed an impact of PCV13 on IPD,
particularly for serotypes 19A and 7F.20 The data of our study are
the first observation indicating the impact of PCV13 on nasopha-
ryngeal flora and the first one describing the biologic effect of
PCV13 on serotype 6C. The induced antibodies against 6B and 6A
are biologically active in vivo, as manifested by the reduction of
nasopharyngeal carriage of 6C. This observation is reassuring
because such an effect on nasopharyngeal carriage is likely to
mean protection against pneumococcal disease in vaccinated chil-

300 | www.pidj.com 2012 Lippincott Williams & Wilkins

The Pediatric Infectious Disease Journal Volume 31, Number 3, March 2012
dren and reduction in the circulation of vaccine serotypes within
the community through the indirect (herd) protection. This illus-
trates the potential interest in the use of PNP carriage as an end
point to assess the efficacy of new pneumococcal vaccines as it
has been recently discussed.21 One of the limitations of the
study is that we have enrolled only children with AOM. Be-
cause nasopharyngeal flora of normal children could be very
different, further studies are needed to assess the impact of
PCV13 on this population.
ACKNOWLEDGMENTS
The authors thank all pediatricians who participated in the
study: C. Abt-Nord, M.-J. Aim-Mille, D. Allain, M. Amzallag, I.
Aubier, P. Bakhache, J. Baron, B. Baszanger, G. Beley, M. Benani,
C. Bensoussan-Ambacher, E. Billard, L. Billet, J.-P. Blanc, M.-J.
Bodin, E. Boez, B. Bohe, J. Bougle, F. Bouillot, J.-L. Cabos, P.
Camier, F. Ceccato, D. Clavel, C. Claverie, R. Cohen, L. Coica-
dan, F. Corrard, L. Cret, B. de Brito, F. De Grenier, P. Deberdt,
I. Defives, A. Delatour, V. Derkx, V. Desvignes, M. Dogneton, I.
Donikian-Pujol, M. Dubosc, C. Dumont, A. Elbez, J. Elbhar, N.
Elkhoury, C. Ferte-Devin, J.-M. Fiorini, D. Garel, J.-L. Gasnier,
A. Gasser, B. Gaudin, N. Gelbert-Baudino, C. Georgeot, M.
Gerardin, M. Giorno, R. Gorge, J.-L. Guillon, J.-F. Hassan, A.
Hayat, P. Huguet, M. Hunin, A. Kalindjian, K. Kassmann, Z.
Klink, M. Koskas, C. Lastman-Lahmi, M.-C. Lemarchand,
J.-C. Leveque, J. Levy, D. Livon, N. Maamri, M.-O. Mercier-Oger,
C. Messica, A.-S. Michot, J. Miclot, P. Migault, I. Nave, M. Navel,
J.-F. Nicolas, A. Pappo, J. Peguet, C. Perrin, C. Petit, O. Pinard,
A. Piollet, J.-F. Pujol, M.-T. Pujol, Y. Regnard, M. Robert, C.
Turberg-Romain, O. Romain, M.-C. Rondeau, C. Schlemmer, G.
Sivelle, D. Somerville, N. Temam-Basse, J.-M. Thiron, F. Thollot,
J. Vaugeois, F. Vie Le Sage, J.-L. Vuillemin, A. Werner, R.
Wisnewsky, A. Wollner, C. Wollner, C. Ythier. The authors thank
M. Boucherat, M. Chalumeau, S. Bechet, B. Fritzell, E. Bonnet,
and S. Attal. The authors thank N. Kohn, S. Tortorelli, and M.
Pereira for technical assistance.
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