Streptococcus pneumoniae, Haemophilus infl uenzae,
Moraxella catarrhalis, and Staphylococcus aureus often
colonize the nasopharynx. Children are susceptible to bac-
terial infections during or soon after upper respiratory tract
infection (URI). We describe colonization with these 4 bac-
teria species alone or in combination during URI. Data were
from a prospective cohort of healthy children 6 to 36 months
of age followed up for 1 year. Analyses of 968 swabs from
212 children indicated that S. pneumoniae colonization is
negatively associated with colonization by H. infl uenzae.
Competitive interactions shifted when H. infl uenzae and M.
catarrhalis colonized together. In this situation, the likeli-
hood of colonization with all 3 species is higher. Negative
associations were identifi ed between S. pneumoniae and S.
aureus and between H. infl uenzae and S. aureus. Polymi-
crobial interactions differed by number and species of bac-
teria present. Antimicrobial therapy and vaccination strate-
gies targeting specifi c bacterial species may alter the fl ora
in unforeseen ways.
ten asymptomatically colonize the nasopharynx of young
children and are also associated with disease. S. pneu-
moniae, H. infl uenzae, and M. catarrhalis are the 3 most
common otitis media pathogens (1,2). S. pneumoniae are
also common causes of pneumonia, sepsis, and meningitis
in young children (3). The proportion of young children
colonized with any of these 3 bacteria species can be >50%
in certain populations (4–6). S. aureus strains colonize up
to 35% of young children and are associated with a wide
range of diseases including soft tissue infections, sepsis,
and pneumonia (7,8). Increases in the incidence of disease
caused by community-acquired methicillin-resistant S. au-
reus are of great concern (9).
Host factors have been shown to infl uence coloniza-
tion with S. pneumoniae, H. infl uenzae, M. catarrhalis, and
S. aureus. These include host immunity, age, gender, race,
out-of-home daycare, breastfeeding, and environmental
exposure to tobacco smoke (10). The magnitude of host
effects may differ by bacteria species.
Interactions between bacteria infl uence which species
persist in the nasopharynx (11–13). Bacteria species may
treptococcus pneumoniae, Haemophilus infl uenzae,
Moraxella catarrhalis, and Staphylococcus aureus of-
Mic robial Interac tions during
Upper Respiratory Trac t Infec tions
Melinda M. Pettigrew, Janneane F. Gent, Krystal Revai, Janak A. Patel, and Tasnee Chonmaitree
1584 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 10, October 2008
Author affi liations: Yale School of Public Health, New Haven, Con-
necticut, USA (M.M. Pettigrew, J.F. Gent); and University of Texas
Medical Branch, Galveston, Texas, USA (K. Revai, J.A. Patel, T.
CME ACT IV IT Y
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Upon completion of this activity, participants will be able to:
Identify common bacterial isolates from children with upper respiratory infection
Specify signifi cant interactions between colonizing bacteria during upper respiratory infections
Identify variables associated with higher rates of colonization with
Specify which bacteria is more common in the nasopharynx of children who attend day care
Beverly Merritt, Technical Writer-Editor, Emerging Infectious Diseases. Disclosure: Beverly Merritt has disclosed no relevant fi nancial
Charles P. Vega, MD, Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine, California,
USA. Disclosure: Charles P. Vega, MD, has disclosed that he has served as an advisor or consultant to Novartis, Inc.
Disclosures: Melinda M. Pettigrew, PhD; Janneane F. Gent, PhD; Krystal Revai, MD; Janak A. Patel, MD; and Tasnee Chonmaitree, MD,
have disclosed no relevant fi nancial relationships.
Microbial Interactions during URIs
be positively associated; this occurs when they are found
together more often than would be expected by chance. A
negative association could occur when bacteria compete
within same environment. Several studies have described
a negative association between S. pneumoniae and S. au-
reus (12–16). Understanding of interactions between S.
pneumoniae, H. infl uenzae, M. catarrhalis, and S. aureus
The nasopharyngeal fl ora change over time; the level
of bacteria colonization is higher during upper respiratory
infection (URI) (6,17). Knowledge is lacking regarding S.
pneumoniae, H. infl uenzae, M. catarrhalis, and S. aureus
interactions during URI because colonization studies either
do not examine competitive interactions among all 4 patho-
gens or focus on healthy children (5,11,16,18). Children
are susceptible to secondary bacterial infections during and
after URI (19–21).
A better understanding of polymicrobial interactions
in the nasopharynx is important for several reasons. Colo-
nization is the initial step in the disease process (22, 23).
Colonized children serve as reservoirs for bacterial trans-
mission to others in the community (24). Additionally, an-
tibimicrobial drugs or vaccines, which target specifi c bac-
teria species, may alter polymicrobial interactions in the
nasopharynx and have unanticipated consequences (25,26).
The goals of our study were to 1) describe the prevalence
of colonization with S. pneumoniae, H. infl uenzae, M. ca-
tarrhalis, and S. aureus; 2) evaluate interactions between S.
pneumoniae, H. infl uenzae, M. catarrhalis, and S. aureus;
and 3) estimate the effect of host factors on colonization
with S. pneumoniae, H. infl uenzae, M. catarrhalis, and S.
aureus after a URI in a prospective cohort of young chil-
Study Design and Participants
We used data from a prospective study of otitis media
complications of URI in children at the University of Texas
Medical Branch (UTMB) at Galveston (19,26). The study
was reviewed and approved by the UTMB Institutional
Review Board. The parents of healthy children 6 months
through 3 years of age, who were receiving medical care at
UTMB from January 2003 through March 2007, were in-
vited to enroll their children. Children with chronic medical
problems and anatomic or physiologic defects of the ear or
nasopharynx were excluded.
At enrollment, we collected information about de-
mographic and URI risk factors. Parents were asked to
describe their child’s race and ethnicity. We also ob-
tained information regarding the number of weeks the
child had been breast-fed and the number of hours and
days/week the child currently attended day care. We
ascertained environmental exposure to tobacco smoke
based on self-reports of whether any household members
smoked cigarettes in the home.
The children in our study were followed up for 1 year.
We requested that parents notify study staff when the child
began to exhibit URI symptoms including nasal conges-
tion, rhinorrhea, cough, sore throat, or fever. A study
physician saw children as soon as possible after the onset
of URI symptoms. At each study visit, the study physi-
cian obtained information regarding specifi c URI symp-
toms and examined the child’s ears. The children were
then monitored closely for 3 weeks for the development
of otitis media. The study physician collected a nasopha-
ryngeal swab during the visit for each URI episode and
when acute otitis media or sinusitis was diagnosed. URI
episodes were categorized as the same episode if symp-
toms persisted. An episode of URI was considered new
when symptoms of the previous episode subsided and the
parents noted new symptoms of URI as described above.
Given our prospective study design, many children had
>1 URI episode and some had >1 visit/URI episode. We
collected 1 swab/physician visit. Data regarding antimi-
crobial drug therapy during the past 7 days were collected
by medical record review. A description of the methods is
provided elsewhere (19,26).
A total of 294 children were enrolled in the original
study (19,26). Included in these analyses are data from 212
(72%) children who experienced at least 1 URI, were seen
by a study physician, and had a nasopharyngeal swab col-
lected for bacterial culture. Thus, we excluded 82 children
who did not have a URI and a swab for bacterial culture.
Of these 82 children without URI visits, 35 (59%) were
lost to follow-up in the fi rst 6 months, 13 (38%) were lost
to follow-up in months 7–11, and 34 (17%) completed 1
year of follow up.
Mini-Tip Culturette kits (Becton Dickinson Micro-
biology Systems, Cockeysville, MD, USA) were used for
sample collection. Each swab was streaked onto 1 blood
and 1 chocolate agar plate. We subcultured and identifi ed
suspected isolates of each species as follows: S. pneumo-
niae isolates were identifi ed by using the optochin disk
susceptibility test (Taxo P, Becton Dickinson Microbiol-
ogy Systems), H. infl uenzae isolates were identifi ed by the
Haemophilus ID Quad Plate with Growth Factors (Becton
Dickinson Microbiology Systems), M. catarrhalis isolates
were identifi ed by the API QuadFerm assay (bioMérieux,
Inc., Hazelwood, MO, USA), and S. aureus isolates were
identifi ed by coagulase, catalase, and latex agglutination
test (Staphaurex Plus, Remel, Lenexa, KS, USA).
The main outcomes of interest were the relationships
between bacteria during URI. All statistical analyses were
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 10, October 2008 1585
conducted by using SAS version 9.1 (SAS Institute, Inc.,
Cary, NC, USA). We examined colonization by S. pneumo-
niae, H. infl uenzae, M. catarrhalis, and S. aureus by using
repeated measures logistic regression with generalized es-
timating equations and an autoregressive correlation struc-
ture (AR1) using the procedure PROC GENMOD (SAS
Institute, Inc.). Because each child could potentially have
multiple URI episodes and contribute multiple bacterial
swabs to the analysis, we used a repeated measures design
to take into account variability of multiple samples from
each child. To examine the effect of covariates on each bac-
teria species, we modeled colonization by S. pneumoniae,
H. infl uenzae, and M. catarrhalis separately. We did not
separately model the outcome of colonization by S. aureus
because of low numbers of isolates obtained. Each model
included the presence or absence of other bacteria species,
as well as potential sampling-time confounders comprising
time of swab collection after URI onset, antimicrobial drug
therapy within the past 7 days, and age of the child at the
time of swab collection. Host factors included in the model
were gender, race, day care, breast-fed for >4 months, and
environmental exposure to tobacco smoke.
Characteristics of the study participants are shown in
Table 1. The median age of study participants was 12.0
months; mean age was 14.1 (SD 7.4) months. Most chil-
dren were white, were cared for at home, and had not been
breast-fed for >4 months. Children were followed up for a
median of 12 months and a mean of 10.7 (SD 2.8) months.
Individual children contributed between 1 and 20 swab
specimens each (mean [SD] and median of 4.6 [3.8] and 3.0
swabs, respectively) from 1 to 18 URI episodes each (mean
[SD] and median of 4.0 [3.3] and 3.0 episodes, respective-
ly). Overall, at least 1 of the 4 species was isolated from
841 of 968 swab samples (86.9%) from 212 children. Of
the 968 swabs, S. pneumoniae was present in 441 (45.6%),
H. infl uenzae was present in 314 (32.4%), and M. catarrha-
lis was the most common bacteria species identifi ed in 611
(63.1%) swabs. S. aureus was relatively rare in comparison;
69 swabs (7.1%) were positive for this species. The distri-
bution and colonization patterns of the 4 bacteria species by
swab and number of URI visits are shown in Table 2.
Most swabs (849 [87.7%]) were collected within 7
days of URI onset; 119 (12.3%) were taken 8–30 days after
URI onset. Of the 968 swab samples, only 54 (5.6%) were
collected from children who had taken antimicrobial drugs
within the past 7 days. Therefore, most swabs were collect-
ed from children who were not taking antimicrobial drugs
at the time of swab collection (94.5%). Of the 212 children,
205 (>96%) had received at least 1 dose of the 7-valent
pneumococcal conjugate vaccine (PCV7) at the time of en-
rollment. Most of the children had received all age-appro-
priate scheduled PCV7 vaccinations at their URI visit, 666
(69%) of samples were collected from children who had
received the age-appropriate number of PCV7 doses at the
time of swab collection. There was no association between
being up to date with PCV7 vaccination and colonization
with S. pneumoniae (p = 0.71). We did not further examine
the effect of the pneumococcal vaccine further because of
the high level of coverage in our study population.
Repeated measures logistic regression models predict-
ing colonization by S. pneumoniae, H. infl uenzae, or M.
catarrhalis are shown in Table 3. A positive association
between bacteria is indicated by an odds ratio (OR) ≥1; a
negative association is indicated by an OR <1. An OR of
1.0, or any 95% confi dence interval that includes 1.0 indi-
cates no signifi cant association. The model predicting colo-
nization by S. pneumoniae indicated that colonization by H.
infl uenzae was negatively associated with S. pneumoniae.
However, when H. infl uenzae and M. catarrhalis colonized
together, they were positively associated with S. pneumo-
niae colonization. Colonization by S. aureus resulted in
1586 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 10, October 2008
Table 1. Characteristics of study participants enrolled through the
University of Texas Medical Branch, Galveston, Texas, USA,
Age at enrollment, mo
Hispanic or Latino
Breast-fed for >4 mo
Environmental exposure to tobacco smoke‡
*Data given for 212 participants who experienced at least 1 upper
respiratory infection, were seen by a study physician, and had a
nasopharyngeal swab collected for bacterial culture. An additional 82
enrollees were excluded from the study because they did not experience
an upper respiratory infection and did not have a nasopharyngeal swab
collected for bacterial culture. Some numbers do not add up to 212
because of missing data.
†No. hours and days/week in day care were grouped into any or none.
‡Environmental exposure to tobacco smoke was based on parental self-
Microbial Interactions during URIs
a 40% reduction in the odds of S. pneumoniae coloniza-
tion. Older children were less likely to be colonized with S.
pneumoniae; each 1-month increase in age was associated
with a 2% decrease in the odds of S. pneumoniae coloni-
zation (Table 3). Antimicrobial drug therapy in the past 7
days was associated with decreased odds of S. pneumoniae
colonization. The timing of swab collection after onset of
URI symptoms and host characteristics such as gender,
race, daycare, breastfeeding, and environmental exposure
to tobacco smoke were not associated with colonization by
In our model examining H. infl uenzae colonization as
the outcome, H. infl uenzae was negatively associated with
S. pneumoniae, M. catarrhalis, and S. aureus (Table 3). In
contrast to their association with S. pneumoniae coloniza-
tion, age and antimicrobial drug therapy during the past 7
days were not signifi cantly associated with colonization
by H. infl uenzae. Host characteristics were associated with
colonization by H. infl uenzae. Male gender and out-of-
home daycare were associated with increased odds of H.
infl uenzae colonization. White race was associated with
decreased odds of H. infl uenzae colonization.
Our third model examined factors associated with col-
onization by M. catarrhalis (Table 3). H. infl uenzae was
negatively associated with colonization by M. catarrha-
lis, but when H. infl uenzae and S. pneumoniae colonized
together, they were positively associated with coloniza-
tion by M. catarrhalis. Older children were less likely to
be colonized with M. catarrhalis; each 1-month increase
in age was associated with a 2% decrease in the odds of
M. catarrhalis colonization (Table 3). Antimicrobial drug
therapy in the past 7 days was associated with decreased
odds of M. catarrhalis colonization. The timing of swab
collection after onset of URI symptoms and host charac-
teristics such as gender, race, daycare, breastfeeding, and
environmental exposure to tobacco smoke were not associ-
ated with colonization by M. catarrhalis.
We describe nasopharyngeal colonization of children
with S. pneumoniae, H. infl uenzae, M. catarrhalis, and S.
aureus alone or in combination during URI. Our models
predicting S. pneumoniae colonization indicated that H.
infl uenzae is negatively associated with S. pneumoniae.
However, when H. infl uenzae was present with M. ca-
tarrhalis, odds of S. pneumoniae colonization increased
by >2-fold. Models predicting H. infl uenzae colonization
indicated a negative association with S. pneumoniae, M.
catarrhalis, and S. aureus. Competitive interactions be-
tween bacteria are complex after URI and may shift from
negative to positive when additional bacteria species are
present. Modeling S. pneumoniae, H. infl uenzae, and M.
catarrhalis colonization separately showed that gender,
race, and daycare were associated with colonization by H.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 10, October 2008 1587
Table 2. Distribution of bacteria on nasopharyngeal swabs collected from children with URI, University of Texas Medical Branch,
Galveston, Texas, USA, 2003–2007*
Total no. (%)
Total no. patients 212
Total no. swabs 968
Bacteria present (% of no. of swabs in each visit category)
0 127 (13.1)
S. pneumoniae, H. influenzae28 (2.9)
S. pneumoniae, M. catarrhalis187 (19.3)
S. pneumoniae, S. aureus8 (0.8)
H. influenzae, M. catarrhalis67 (6.9)
H. influenzae, S. aureus3 (0.3)
M. catarrhalis, S. aureus17 (1.8)
S. pneumoniae, H. influenzae, M. catarrhalis
S. pneumoniae, H. influenzae, S. aureus
S. pneumoniae, M. catarrhalis, S. aureus
H. influenzae, M. catarrhalis, S. aureus
*URI, upper respiratory tract infection.
†Data are presented as no. of physician visits/child. Because of our prospective study design, many children had >1 URI episode during the follow-up
period, and some had >1 physician visit/URI episode. One nasopharyngeal swab sample was taken at each physician visit.
No. (%) URI visits†
42 (19.8) 38 (17.9)
84 (8.7) 128 (13.2)
12 5–6 >6
9 (19.6) 9 (10.7) 13 (10.2) 19 (9.4) 77 (15.1)
1 ( 2.2)
infl uenzae, but not with colonization by either S. pneumo-
niae or M. catarrhalis.
Jacoby et al. used a multivariate random effects mod-
el to examine S. pneumoniae colonization in Aboriginal
and non-Aboriginal children in Australia (11). Their study
differed from ours in that they examined the relationship
between S. pneumoniae, H. infl uenzae, M. catarrhalis,
and S. aureus in pairwise combinations. These research-
ers also examined healthy children; we examined children
who had a URI. Jacoby et al. observed positive associa-
tions between pairwise combinations of S. pneumoniae
and H. infl uenzae and between S. pneumoniae and M. ca-
tarrhalis. They did not identify an association between S.
pneumoniae and S. aureus or between H. infl uenzae and
S. aureus (11).
Our results confi rm a recent report describing a nega-
tive association between H. infl uenzae and S. aureus in
HIV-negative children (12). Our data also support a grow-
1588 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 10, October 2008
Table 3. Predicted outcome of colonization with Stretococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis in young
children after upper respiratory tract infection (968 swabs from 212 children; see Table 2)*
OR (95% CI)
H. influenzae x M. catarrhalis (p = 0.0003)†
H. influenzae only
M. catarrhalis only
S. pneumoniae x M. catarrhalis (p = 0.08)†
S. pneumoniae only
M. catarrhalis only
H. influenzae x S. pneumoniae (p<0.0001)†
H. influenzae only
S. pneumoniae only
Age (1-mo increase)‡
Antimicrobial drug therapy in past 7 days
Time after URI onset, d
Not white (reference)
Breast-fed >4 mo
Environmental exposure to tobacco smoke
*OR, odds ratio; CI, confidence interval. Significant ORs and 95% CIs are shown in boldface. Each model included variables representing presence or
absence of other bacteria as well as all other variables listed. We did not model colonization of S. aureus because of low prevalence of this species
(69/968 positive swabs).
†p value from logistic regression model for overall significance of bacterial interaction.
‡Age (mo) of the child at the time of swab collection.
S. pneumoniae M. catarrhalis
1.47 (0.96–2.27) 1.10 (0.70–1.73) 1.21 (0.81–1.80)
1.0 1.0 1.0
0.94 (0.69–1.29) 0.92 (0.65–1.29) 0.81 (0.59–1.12)
1.0 1.0 1.0
1.13 (0.84–1.52) 0.93 (0.69–1.27) 0.91 (0.67–1.23)
Microbial Interactions during URIs
ing body of literature describing negative associations be-
tween S. pneumoniae and S. aureus (12–15). For example,
a cross-sectional study of 790 children younger than 40
months identifi ed a negative association between S. pneu-
moniae colonization and S. aureus (OR 0.47; 95% confi -
dence interval 0.28–0.78) (13).
An in vivo mouse model of competitive interactions
between S. pneumoniae and H. infl uenzae has suggested
mechanisms to explain our observations (27). Both S. pneu-
moniae and H. infl uenzae successfully colonized BALBc/
SCID mice when each bacteria species was injected sepa-
rately. However, S. pneumoniae was cleared rapidly when
H. infl uenzae was present in a co-colonization model. The
competitive interaction between H. infl uenzae and S. pneu-
moniae was dependent on complement and neutrophils
(27). These researchers proposed that H. infl uenzae cellular
components activate the host innate immune response, thus
killing S. pneumoniae (27). M. catarrhalis was not exam-
ined in this model, but our data suggest that the additional
presence of M. catarrhalis might alter the competitive bal-
ance between S. pneumoniae and H. infl uenzae and that all
3 bacteria species would successfully colonize.
In vitro studies have also demonstrated competition
between H. infl uenzae and S. pneumoniae but predicted
that S. pneumoniae should inhibit the growth of H. infl u-
enzae. Neuraminidase A is produced by S. pneumoniae and
cleaves sialic acid. It has been shown to remove sialic acid
from lipopolysaccharides of H. infl uenzae strains (28), po-
tentially giving pneumococci a competitive advantage by
making H. infl uenzae more susceptible to complement-me-
diated clearance. Furthermore, in vitro co-culture experi-
ments indicate that S. pneumoniae can inhibit H. infl uenzae
through the action of hydrogen peroxide (29). Interference
between S. pneumoniae and S. aureus may also be caused
by hydrogen peroxide production by S. pneumoniae (30).
Our results indicate that antimicrobial drug therapy
in the past 7 days was associated with a lower prevalence
of colonization with S. pneumoniae or M. catarrhalis. In
contrast, antimicrobial drug therapy in the past 7 days was
not associated with colonization by H. infl uenzae. Varon et
al. studied the effect of antimicrobial drugs on colonization
with S. pneumoniae, H. infl uenzae, and M. catarrhalis in
a cohort of young children with URI (31). Children in this
study received antimicrobial drugs for a mean treatment pe-
riod of 8 days. Swab samples were taken before treatment
and on days 2 through 6 after treatment. Results showed
that colonization by S. pneumoniae, H. infl uenzae, and M.
catarrhalis decreased after antimicrobial drug therapy (31).
The magnitude of the effect differed by bacteria species
and the specifi c antimicrobial drug prescribed. In general,
antimicrobial drugs were less effective for reducing coloni-
zation with H. infl uenzae than with S. pneumoniae and M.
The effect of age, gender, race, and breastfeeding on
colonization differs by population studied (10). Daycare
has consistently been associated with increased levels of
colonization with S. pneumoniae, H. infl uenzae, and M.
catarrhalis (10), as has exposure to other children in the
household (32,33). Our study was limited by lack of data
on age and number of siblings or other potential confound-
ers such as household crowding and socioeconomic status.
Our study had additional limitations. A cross-sectional
study of S. aureus and S. pneumoniae colonization indicat-
ed a negative association between PCV7 vaccine serotypes
and S. aureus (15). No association was found between S.
pneumoniae nonvaccine types and S. aureus. We were un-
able to examine the association between S. pneumoniae se-
rotype and colonization. Along these lines, we did not have
data regarding H. infl uenzae type B vaccination status and
did not serotype our H. infl uenzae strains. Therefore, we
were also unable to evaluate the effect of this vaccination
on polymicrobial colonization.
Nasopharyngeal colonization likely involves a com-
plex combination of factors including host characteristics
that infl uence exposure to specifi c bacterial species, host
immune responses that may result in killing the bacteria,
and direct competitive interactions between bacteria spe-
cies. In addition to the inhibiting effects of neuraminidase
A and hydrogen peroxide already described, competitive
interactions between bacteria may also include the secre-
tion of small peptide inhibitors, competition for nutrients,
and competition for receptor binding sites. It is also pos-
sible that the presence of 1 bacteria species could create
a more hospitable niche for another bacteria species. We
were unable to evaluate the precise molecular mechanisms
that mediate these complex polymicrobial interactions, an
important area for future research.
Our study had several strengths, including its longi-
tudinal, prospective design. We examined nasopharyngeal
carriage during URI, a time when children are at risk for
secondary bacterial infections. In addition, we took advan-
tage of repeated measures analytic techniques to examine
microbe-level factors infl uencing bacterial colonization
while controlling for host factors.
Results from our study have public health implica-
tions. Scientists have debated whether they should seek to
eradicate disease by preventing nasopharyngeal coloniza-
tion (34). Vaccines targeting nasopharyngeal carriage of
S. pneumoniae, H. infl uenzae, and M. catarrhalis may be
needed to prevent otitis media because simultaneous car-
riage of these 3 bacteria may increase risk for otitis media
(35). Our data indicate that the elimination of nasopha-
ryngeal colonization with bacteria such as S. pneumoniae
and H. infl uenzae may increase risk for colonization with
S. aureus. Scientists conducting a randomized trial of
the effectiveness of pneumococcal vaccines noted an in-
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 10, October 2008 1589
crease in S. aureus when spontaneously draining infected
middle ears of vaccinated children (25). Factors that may
increase the risk of colonization with S. aureus are of spe-
cial concern given the spread of methicillin-resistant S.
aureus (9). Researchers are attempting to develop an S.
pneumoniae vaccine containing pneumococcal choline
binding protein A, which would protect against sepsis and
pneumonia without interfering with pneumococcal colo-
nization (36). Although this type of vaccination strategy
may eventually decrease the incidence of potentially fatal
invasive pneumococcal disease, it is unlikely to prevent
otitis media. Thus, the public health impact of a given
intervention strategy may be hard to predict, and caution
should be used when designing control strategies that tar-
get nasopharyngeal colonization.
The authors thank M. Lizette Rangel, Kyralessa B. Ramir-
ez, Syed Ahmad, Michelle Tran, Liliana Najera, Rafael Serna,
and Carolina Pillion for assistance with study participants. We
also thank Sangeeta Nair and Nahed Ismail for assistance in the
This work was supported by grants R01 DC005841 and DC
005841-02S1 from the National Institutes of Health. The study
was conducted at the General Clinical Research Center at the Uni-
versity of Texas Medical Branch, which is funded by National
Center for Research Resources (National Institutes of Health, US
Public Health Service), grant M01 RR 00073.
Dr Pettigrew is on the faculty at the Yale School of Public
Health. Her research interests include the epidemiology and mo-
lecular epidemiology of pediatric infectious diseases.
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2004;23:824–8. DOI: 10.1097/01.inf.0000136871.51792.19
3. Hausdorff WP. Invasive pneumococcal disease in children: geo-
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Address for correspondence: Melinda M. Pettigrew, Yale University
School of Public Health, 60 College St, New Haven, CT 06520-8034,
USA; email: email@example.com
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