Journal of Medical Microbiology (2012), 61, 678–685
DOI 10.1099/jmm.0.040584-0
Nasal colonization by four potential respiratory
bacteria in healthy children attending kindergarten
or elementary school in Seoul, Korea
Songmee Bae,1 Jae-Yon Yu,1 Kwangjun Lee,2 Sunhwa Lee,3
Bohyun Park3 and Yeonho Kang1
Correspondence
Yeonho Kang
[email protected]
1
Division of Bacterial Respiratory Infections, Center for Infectious Diseases, National Institute of
Health, Centers for Disease Control and Prevention, Chungcheongbuk-do, Republic of Korea
2
Division of High-Risk Pathogen Research, Center for Infectious Diseases, National Institute of
Health, Centers for Disease Control and Prevention, Chungcheongbuk-do, Republic of Korea
3
Research Service Division Academic Team, NeoDin Medical Institute, Seoul, Republic of Korea
Received 13 November 2011
Accepted 23 January 2012
A longitudinal analysis was carried out of the colonization by four potential respiratory pathogens
– Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and
Staphylococcus aureus – in 165 healthy children (aged 3–7 years) attending three
kindergartens and 417 healthy children (aged 7–10 years) attending an elementary school in
Seoul, Korea, by four consecutive examinations over 1 year. The prevalence of nasal carriers of
one or more of four bacteria was found to be higher in younger children (¡7 years) (mean
68.6 %) than that in older children (mean 46.8 %). The mean rates of nasal carriage of Strep.
pneumoniae, H. influenzae, M. catarrhalis and Staph. aureus were 16.8, 18.9, 20.2 and 18.2 %,
respectively. Colonization by Strep. pneumoniae, H. influenzae and M. catarrhalis was higher in
pre-school children (28.6, 32.4 and 35.0 %, respectively) than in school children (12.2, 13.6
and 14.3 %, respectively). Carriage trends differed with age, with Strep. pneumoniae, H.
influenzae and M. catarrhalis colonization decreasing with age but Staph. aureus colonization
increasing. Positive associations of co-occurrence between Strep. pneumoniae, H. influenzae
and M. catarrhalis were evident, with a significant negative association evident between Staph.
aureus and the other three bacteria. A better understanding of the colonization and interaction of
potential respiratory pathogens may be important for predicting changes in bacterial ecology
and for designing control strategies that target bacterial colonization in upper respiratory tract
infections.
INTRODUCTION
Respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and
Staphylococcus aureus can asymptomatically colonize the
human upper respiratory tract (URT) (i.e. nose and
throat). The result can be various respiratory infections,
as well as invasive diseases (Marchisio et al., 2001; Jacobs
et al., 2003).
In the human URT, bacterial colonization is a dynamic
process in which bacteria are acquired, eliminated and
reacquired many times during a human life and can be
influenced by various factors such as host age, immune
status, exposure to antibiotics, smoking and overcrowded
Abbreviations: OR, Odds ratio; PCV7, 7-valent pneumococcal conjugate
vaccine; URT, upper respiratory tract.
678
living conditions (Marchisio et al., 2001; Garcı́a-Rodrı́guez
& Fresnadillo Martı́nez, 2002; Chen et al., 2007; Mukundan
et al., 2007).
Most carriage studies have focused on individually
evaluating colonization by a single bacterium (O’Brien
et al., 2003; Farjo et al., 2004; Greenberg et al., 2004).
Recently, some carriage studies have reported the cooccurrence of a number of bacteria and suggested direct
interactions such as interference or competition between
the various bacterial species in the URT (Jacoby et al.,
2007; Pettigrew et al., 2008). Although knowledge is
limited, a change of colonization pattern of potential
pathogens in the URT may have an effect on both the
development of disease and the spread of pathogens in
an individual. Thus, the composition of the various nasal
potential pathogens is crucial in understanding bacterial
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Nasal colonization by potential respiratory bacteria
interactions, interpreting disease epidemiology and designing control strategies for diseases caused by these respiratory
pathogens.
The Korean Ministry of Health and Welfare has reported
that the number of Korean children ¡5 years of age in
day-care facilities or attending kindergarten is 62.8 %
(1 690 000 and 2 690 000 children, respectively) (Korean
Ministry of Health and Welfare, 2010). Thus, in Korean
society, many of its youngest children are likely to be
exposed to respiratory pathogens. There has been no
comprehensive longitudinal study of the colonization
patterns of potential respiratory pathogens in young
children in Asia. To understand the bacterial colonization
in young children exposed to a crowded urban environment, we designed the present study to monitor the
prevalence of nasal carriage and co-colonization patterns
of Strep. pneumoniae, H. influenzae, M. catarrhalis and
Staph. aureus in healthy pre-school and school children in
Seoul, Korea. This longitudinal study involved three
kindergartens and one elementary school, with measurements taken four times during the year-long period of
study.
METHODS
Study design. This study was designed to investigate longitudin-
ally the nasal carriage of four potential respiratory bacteria in
healthy children aged 3–10 years, attending kindergarten or the
first 2 years of elementary school in Seoul, Korea, over a 1-year
period. A total of 582 children from three kindergartens and one
elementary school were enrolled in this study. They comprised 165
children (28.4 %) aged 3–7 years attending three kindergartens and
417 children (71.6 %) aged 7–10 years attending an elementary
school (grade 1, seven classes, n5212; grade 2, seven classes,
n5205). The mean ages were 5.6±1.2 and 8.4±0.6 years,
respectively, in the two groups. Approximately half of the
participants were male (51.0 %). A total of 2328 nasal aspirates
were obtained from the 582 children at four time points: June 2006
(summer), September 2006 (autumn), December 2006 (winter)
and February 2007 (late winter).
This study was approved by the Research Ethics Committee of the
Korea Centers for Disease Control and Prevention. In all cases,
parental informed consent was obtained and a written questionnaire
was completed by each participant’s parent regarding the subject’s
age, gender and history of recent respiratory infections and antibiotic
therapy.
Sample collection. We visited each classroom in the three
kindergartens and the elementary school and collected nasal aspirates
from enrolled children displaying no signs of respiratory infections.
For the collection, a sterile physiological saline solution was instilled
into one of the child’s nostrils and the mucus was recovered through a
tube introduced into the nostril. The mucus was emptied individually
into a specially designed sterile container connected to a portable
suction apparatus. All specimens were transported to the microbiology laboratory of the NeoDin Medical Institute, Seoul, Korea, within
4 h of collection.
Laboratory procedures. On arrival at the laboratory, the nasal
aspirates were inoculated onto sheep blood agar and chocolate agar
plates (KOMED) and incubated at 35 uC for 24 h in 5 % CO2. Each
http://jmm.sgmjournals.org
sample was analysed for the presence of Strep. pneumoniae, H.
influenzae, M. catarrhalis and Staph. aureus. Each bacterial isolate was
subcultured and identified by standard laboratory procedures. Strep.
pneumoniae was identified by colony morphology, a-haemolysis,
Gram staining, optochin susceptibility and bile solubility. H.
influenzae was identified by Gram straining, X factor (haemin)/V
factor (nicotinamide adenine dinucleotide) requirement and an API
NH kit (bioMérieux). M. catarrhalis was identified by Gram staining,
catalase and oxidase tests and an API NH kit. Staph. aureus was
identified by coagulase and catalase tests and the Vitek system
(bioMérieux).
Data analysis. All statistical analysis was performed using
SAS
software version 9.2 (SAS Institute) as appropriate. For all comparisons, P,0.05 was considered statistically significant. The relationship between Strep. pneumoniae, H. influenzae, M. catarrhalis and
Staph. aureus in healthy children was analysed using a logistic regression model (Pettigrew et al., 2008).
RESULTS AND DISCUSSION
Carriage rates of Strep. pneumoniae, H.
influenzae, M. catarrhalis and Staph. aureus
Table 1 shows the nasal carriage rate for the individual
bacteria in healthy children. Among the 582 children, the
carriage rates of Strep. pneumoniae were 17.2, 15.8, 19.8
and 14.6 % (mean 16.8 %) at the four sampling times,
whilst H. influenzae carriage rates were 19.9, 14.6, 21.1 and
19.9 % (mean 18.9 %). The prevalence of colonization by
M. catarrhalis gave a mean value of 20.2 %, ranging from
17.4 to 26.0 % at the four sampling times.
Colonization by Staph. aureus ranged from 14.1 to
23.9 % (mean 18.2 %). There was no significant difference in the carriage rate of the four bacteria among all
the children. However, when comparing the carriage
rate between the two age groups, the prevalence of nasal
colonization by each bacterium was significantly affected
by the children’s age. Strep. pneumoniae, H. influenzae
and M. catarrhalis were significantly more prevalent
(means of 28.6, 32.4 and 35.0 %, respectively) in younger
children attending kindergarten and less prevalent (means
of 12.2 %, 13.6 %, and 14.3 %, respectively) in pupils in
grades 1 and 2 (P,0.0001). In contrast, colonization by
Staph. aureus was higher in elementary-school pupils
(20.6 %) compared with younger children (12.2 %)
(P,0.0001).
Nasal colonization of four respiratory bacteria
Table 2 shows the frequencies of nasal colonization by one
or more of the four respiratory pathogens at each of the
four sampling times. Of the total 582 children, 325
(55.8 %) were colonized with at least one of the species
in June 2006, 318 (54.6 %) in September 2006, 314
(54.0 %) in December 2006 and 276 (47.4 %) in February
2007. No seasonal variation in the nasal carriage of the four
bacteria was apparent. Interestingly, about half of the
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679
680
100 92 (15.8) 115 85 (14.6) 116 (19.9) 85 (14.6) 123 (21.1) 116 (19.9) 111 (19.1) 106 (18.2) 151 (26.0) 101 (17.4) 113 (19.4) 139 (23.9) 82 (14.1) 89 (15.3)
(17.2)
(19.8)
P,0.0001
P ,0.0001
P ,0.0001
P ,0.0001
58 (28.3)
20 (9.8)
15 (7.3)
13 (6.3)
Kindergarten
(n5165)
Elementary
school
(n5417)
Grade 1
(n5212)
Grade 2
(n5205)
Total
(n5582)
Trend for age
17 (8.3)
8 (3.9) 36 (17.6) 13 (6.3) 25 (12.2) 20 (9.8) 35 (17.1)
19 (9.3)
35 (17.1)
57 (27.8) 29 (14.1) 35 (17.1)
38 (17.9)
21 (9.9)
28 (13.2)
34 (16.0)
38 (17.9) 28 (13.2) 46 (21.7) 17 (8.0) 29 (13.7) 19 (9.0) 51 (24.1)
44 (20.8)
56 (26.4)
57 (26.9) 27 (12.7) 42 (19.8)
96 (23.0) 114 (27.3) 56 (13.4) 77 (18.5)
41 (9.8)
43 (10.3)
47 (11.3)
55 (13.2) 36 (8.6) 82 (19.7) 30 (7.2) 54 (12.9) 39 (9.4) 86 (20.6)
63 (15.1)
91 (21.8)
25 (15.2) 26 (15.8) 12 (7.3)
17 (10.3)
60 (36.4)
63 (38.2)
69 (41.8)
45 (27.3) 56 (33.9) 33 (20.0) 55 (33.3) 62 (37.6) 46 (27.9) 37 (22.4)
48 (29.1)
60 (36.4)
Sep
Dec
Feb
Jun
Feb
Dec
Sep
Jun
Sep
Dec
Feb
Jun
Sep
Dec
Feb
Jun
Staph. aureus
M. catarrhalis
H. influenzae
Strep. pneumoniae
Group
Values represent number of carriers followed by the percentage in parentheses.
Table 1. Comparison of nasal carriage rates of Strep. pneumoniae, H. influenzae, M. catarrhalis and Staph. aureus among kindergarten and elementary-school children
measured in June, September and December 2006 and February 2007
S. Bae and others
participants were non-carriers at each sampling time point,
with rates ranging from 44.2 to 52.6 % according to the
sampling points.
Comparison of the two groups showed that the prevalence of nasal carriage with one or more of the bacteria
was higher in the younger kindergarten children than in
the elementary-school children over the four periods
(P,0.0001). Overall carriage rates of one or more bacteria
were 68.6 % in the 165 children attending kindergarten and
46.8 % in the 417 children attending elementary school
during the study.
Frequency of simultaneous carriage of the four
respiratory bacteria
Table 2 shows the co-colonization patterns of the four
bacteria according to sampling time and age group. Over
half of the school children (53.2 %) did not carry any of
the four bacterial species in their nasal cavities. All four
bacterial species were absent in 31.4 % of kindergarten
children (P,0.0001). Whilst the most frequent carriers of
M. catarrhalis were kindergarten children (13.2 %), the
prevalence of carriers of Staph. aureus only was highest
(18.4 %) in the elementary-school children.
With regard to the overall carriage rate with a single
bacterium, 6.1 and 4.4 % of kindergarten and elementary-school children, respectively, harboured Strep. pneumoniae alone, 9.4 and 5.2 % harboured only H.
influenzae, 13.2 and 7.6 % harboured only M. catarrhalis
and 8.5 and 18.4 % harboured only Staph. aureus.
Carriers of more than one bacterial species were
common: 45.9 % of positive samples (208/453) contained
more than one bacterium in kindergarten children and
23.8 % of positive samples (186/780) in elementaryschool children. In addition, the frequencies of simultaneous co-colonization of two or three bacteria were
generally higher for kindergarten children than for
elementary-school children.
In kindergarten and elementary-school children, the overall
rates of carriage of Strep. pneumoniae and H. influenzae
together were 7.4 and 3.0 % (P,0.0001), rates of carriage
of Strep. pneumoniae and M. catarrhalis together were
6.1 and 1.7 % (P,0.0001), and rates of carriage of H.
influenzae and M. catarrhalis together were 6.2 and 1.9 %
(P,0.0001), respectively. It is of note that the concurrent
carriage rates of the three bacteria Strep. pneumoniae,
H. influenzae and M. catarrhalis were 7.6 and 2.3 %
(P,0.0001) for the kindergarten and elementary-school
children, respectively.
Association between colonization of the four
bacteria
Table 3 summarizes the association between nasal cocolonization of Strep. pneumoniae, H. influenzae, M.
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Journal of Medical Microbiology 61
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Table 2. Comparison of nasal colonization patterns of Strep. pneumoniae, H. influenzae, M. catarrhalis and Staph. aureus in kindergarten and elementary-school children
measured in June, September and December 2006 and February 2007
Values represent number of carriers followed by the percentage in parentheses.
Colonizing organism
Kindergarten (n5165)
Jun
Sep
Dec
Feb
Elementary school (n5417)
Total
(n5660)
Jun
219
198
167
17
18
29
103
28
11
4
3
4
3
3
3
1
(52.5)
(47.5)
(40.1)
(4.1)
(4.3)
(7.0)
(24.7)
(6.7)
(2.6)
(1.0)
(0.7)
(1.0)
(0.7)
(0.7)
(0.7)
(0.2)
0 (0.0)
0 (0.0)
2 (0.5)
*Carriers were defined as children colonized with one or more bacterial species.
681
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Dec
210
207
130
21
26
38
45
46
16
11
3
12
2
2
33
27
(50.4)
(49.6)
(31.1)
(5.0)
(6.2)
(9.1)
(10.8)
(11.0)
(3.8)
(2.6)
(0.7)
(2.9)
(0.5)
(0.5)
(7.4)
(6.5)
1 (0.2)
3 (0.7)
0 (0.0)
Feb
256
161
129
12
24
24
69
30
10
6
0
7
3
4
2
1
(61.4)
(38.6)
(31.0)
(2.9)
(5.8)
(5.8)
(16.5)
(7.2)
(2.4)
(1.4)
(0.0)
(1.7)
(0.7)
(1.0)
(0.4)
(0.2)
0 (0.0)
0 (0.0)
1 (0.2)
Total
(n51668)
888
780
593
72
87
127
307
139
50
29
7
31
13
9
47
38
(53.2)
(46.8)
(35.6)
(4.4)
(5.2)
(7.6)
(18.4)
(8.3)
(3.0)
(1.7)
(0.4)
(1.9)
(0.8)
(0.5)
(2.8)
(2.3)
1 (0.1)
4 (0.2)
4 (0.2)
,0.0001
,0.0001
0.088
0.001
,0.0001
,0.0001
,0.0001
,0.0001
0.305
,0.0001
0.041
0.320
,0.0001
0.141
0.989
0.239
Nasal colonization by potential respiratory bacteria
None carriers
54 (32.7) 45 (27.3) 58 (35.2) 50 (30.3) 207 (31.4) 203 (48.7)
Carriers*
111 (67.2) 120 (72.7) 107 (64.8) 115 (69.7) 453 (68.6) 214 (51.3)
One pathogen only
62 (37.5) 66 (40.1) 67 (40.6) 50 (30.3) 245 (37.2) 168 (40.3)
S. pneumoniae
7 (4.2)
15 (9.1)
9 (5.5)
9 (5.5)
40 (6.1)
23 (5.5)
H. influenzae
23 (13.9) 10 (6.1)
10 (6.1)
19 (11.5) 62 (9.4)
19 (4.6)
M. catarrhalis
20 (12.1) 25 (15.2) 28 (17.0) 14 (8.5)
87 (13.2) 36 (8.6)
S. aureus
12 (7.3)
16 (9.7)
20 (12.0)
8 (4.8)
56 (8.5)
90 (21.6)
Two pathogens
37 (22.3) 38 (23.1) 29 (17.5) 47 (28.5) 151 (23.0) 35 (8.3)
S. pneumoniae+H. influenzae
17 (10.3) 12 (7.3)
6 (3.6)
14 (8.5)
49 (7.4)
13 (3.1)
S. pneumoniae+M. catarrhalis
8 (4.8)
12 (7.3)
8 (4.8)
12 (7.3)
40 (6.1)
8 (1.9)
S. pneumoniae+S. aureus
1 (0.6)
2 (1.2)
1 (0.6)
1 (0.6)
5 (0.8)
1 (0.2)
M. catarrhalis+H. influenzae
7 (4.2)
9 (5.5)
10 (6.1)
15 (9.1)
41 (6.2)
8 (1.9)
M. catarrhalis+S. aureus
1 (0.6)
2 (1.2)
4 (2.4)
2 (1.2)
9 (1.4)
1 (0.2)
H. influenzae+S. aureus
3 (1.8)
1 (0.6)
0 (0.0)
3 (1.8)
7 (1.1)
4 (1.0)
Three pathogens
12 (7.3)
16 (9.7)
11 (6.7)
18 (10.9) 57 (8.7)
11 (2.6)
S. pneumoniae+H. influenzae+
12 (7.3)
12 (7.3)
9 (5.5)
17 (10.3) 50 (7.6)
9 (2.2)
M. catarrhalis
S. pneumoniae+M. catarrhalis+S. aureus
0 (0.0)
2 (1.2)
0 (0.0)
0 (0.0)
2 (0.3)
0 (0.0)
S. pneumoniae+H.influenzae+S. aureus
0 (0.0)
1 (0.6)
0 (0.0)
1 (0.6)
2 (0.3)
1 (0.2)
H. influenzae+M. catarrhalis+S. aureus
0 (0.0)
1 (0.6)
2 (1.2)
0 (0.0)
3 (0.5)
1 (0.2)
Sep
P value
S. Bae and others
catarrhalis and Staph. aureus in healthy children. An odds
ratio (OR) of 1.0 indicates that the presence of one
bacterium is unaffected by the other. A positive correlation
between pairs of bacteria is indicated by an OR .1 and a
negative correlation is indicated by an OR ,1. There was a
significant positive association of co-occurrence between
Strep. pneumoniae, H. influenzae and M. catarrhalis. However, a negative association was identified between Staph.
aureus and the three other bacteria. Staph. aureus colonization resulted in a reduction in the odds of colonization of all
three bacteria in both kindergarten and elementary-school
children.
Colonization of potential respiratory pathogens in the
URT is very common in healthy children (Farjo et al.,
2004). Our longitudinal carriage study indicated that
the carriage of Strep. pneumoniae, H. influenzae and M.
catarrhalis was more prevalent in younger children, but
Staph. aureus carriage was more frequent in older children. Positive associations of co-occurrence were evident
between Strep. pneumoniae, H. influenzae and M.
catarrhalis, but a significant negative association was
evident between Staph. aureus and the other three
bacteria. However, the results of carriage studies vary
considerably from study to study. It is difficult simply to
compare the carriage rates of potential respiratory
pathogens because of the influence of numerous factors
such as age, geographical area, sampling site, sampling
technique, immunization programme and socio-economic conditions (Auranen et al., 2010; Gunnarsson
et al., 1998).
One of the drawbacks of this study was that we did not
undertake an accurate investigation of H. influenzae type
b (Hib) vaccine and 7-valent pneumococcal conjugate
vaccine (PCV7) immunization in the recruited children.
Moreover, these are not currently included in the National Immunization Programme and would have been
administrated to infants through private clinics in Korea.
Thus, we could not determine how far the immunization of these two vaccines influenced the results of this
study.
In contrast to many studies for young children aged ¡2
years, who have the highest prevalence of carriage, we
focused on two age groups that have been exposed to the
crowded environment of urban life: pre-school children
(3–7 years) and children in grades 1 and 2 of elementary
school (7–9 years). The mean rates of nasal carriage of
Strep. pneumoniae, H. influenzae, M. catarrhalis and
Staph. aureus were 16.8, 18.9, 20.2 and 18.2 %, respectively, of all the children studied. The younger age group
showed a higher carriage rate than the older children.
Colonization of Strep. pneumoniae, H. influenzae and M.
catarrhalis was higher in pre-school children (28.6, 32.4
and 35.0 %, respectively) than in elementary-school
children (12.2, 13.6 and 14.3 %, respectively). These
carriage patterns are consistent with previous studies
682
(Bogaert et al., 2004a; Gunnarsson et al., 1998; RegevYochay et al., 2004).
A study conducted in Sweden reported that the overall
isolation frequencies of Strep. pneumoniae in pre-school
children (,7 years), school children (7–15 years) and
adults were 19.0, 6.0 and 0.8 %, respectively; isolation
frequencies of H. influenzae were 13.0, 6.0 and 3.0 %
and isolation frequencies of M. catarrhalis were 27.0,
4.0 and 2.0 % (Gunnarsson et al., 1998). Another study
reported that colonization of these three bacteria
peaked at 2–3 years of age and decreased gradually
up to 15–16 years (Garcı́a-Rodrı́guez & Fresnadillo
Martı́nez, 2002). In contrast, the colonization patterns
of Staph. aureus differed from those of the other three
bacteria. We also found a higher carriage of Staph. aureus in older children (20.6 %) than in younger children
(12.2 %), resembling the peak incidence of Staph.
aureus carriage at 10 years of age among children in
other studies (Bogaert et al., 2004b; Regev-Yochay et al.,
2004). Collectively, these epidemiological data support
the view that the significant increase in Staph. aureus
carriage in these children may be explained by the interference competition between Staph. aureus and Strep.
pneumoniae and by different host responses to these
bacterial species.
The nasal cavity in the upper airway is the primary
colonization site of many potential respiratory pathogens and commensal species in humans. Interspecies
interactions may influence nasal colonization by potential pathogens in a microbial community that is both
complex and dynamic. To understand the comprehensive associations between Strep. pneumoniae, H. influenzae, M. catarrhalis and Staph. aureus, we analysed the
co-colonization patterns among these four potential
respiratory pathogens in healthy children through a
modelling approach identical to one used previously
(Jacoby et al., 2007). We identified separate positive
associations between Strep. pneumoniae, H. influenzae
and M. catarrhalis. In contrast, co-colonization of Staph.
aureus and the other bacteria was rarer than expected,
with negative associations evident. As a whole, our
findings are consistent with those of an earlier study
conducted in healthy children, except for the relationship between Strep. pneumoniae and Staph. aureus
(Jacoby et al., 2007).
Recent epidemiological studies and in vivo animal studies
have shown subtle but conflicting views of the associations between potential respiratory pathogens in the URT
(Garcı́a-Rodrı́guez & Fresnadillo Martı́nez, 2002; Murphy
et al., 2009). Interbacterial competition between Strep.
pneumoniae and H. influenzae showed contradictory
results (Murphy et al., 2009). Like our results, Jacoby
et al. (2007) reported a positive association between Strep.
pneumoniae and H. influenzae colonization in Aboriginal and non-Aboriginal healthy children in Australia,
whereas Pettigrew et al. (2008) showed that Strep.
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Nasal colonization by potential respiratory bacteria
Table 3. Associations between co-colonization of Strep. pneumoniae, H. influenzae, M. catarrhalis and Staph. aureus
Analysis of 2328 nasal aspirate samples from 582 children. OR, Odds ratio; CI, confidence interval.
Parameter
Associations between S. pneumoniae, H. influenzae and M. catarrhalis
S. pneumoniae
Neither (reference)
H. influenzae
M. catarrhalis
H. influenzae+M. catarrhalis
H. influenzae
Neither (reference)
S. pneumoniae
M. catarrhalis
S. pneumoniae+M. catarrhalis
M. catarrhalis
Neither (reference)
H. influenzae
S. pneumoniae
S. pneumoniae+H. influenzae
Associations between S. aureus and other bacteria
S. pneumoniae
Neither (reference)
S. aureus
H. influenzae
Neither (reference)
S. aureus
M. catarrhalis
Neither (reference)
S. aureus
pneumoniae colonization was negatively associated with
colonization by H. influenzae in American children with
symptoms of an upper respiratory infection. The
present epidemiological data indicated an antagonistic
association between Staph. aureus and the other three
bacteria with regard to colonization. This probably
involves direct killing of one species by another,
mediated by inhibiting effectors such as neuraminidase,
hydrogen peroxide and bacteriocin (Pettigrew et al.,
2008). In particular, a previous in vitro experiment
suggested that hydrogen peroxide produced by Strep.
pneumoniae could inhibit Staph. aureus colonization
(Regev-Yochay et al., 2006). However, a recent study in
neonatal rats (Margolis, 2009) showed a contradictory
result where hydrogen peroxide produced by Strep.
pneumoniae had no significant effect on the colonization of Staph. aureus. One can speculate that the
ecological interaction of bacteria may depend on
nutrients and receptor-binding sites or immune
responses in the same local niche of the host. The
implication of the host immunological response has
been emphasized by a study showing a negative
association between Strep. pneumoniae and Staph.
aureus in children who were immunocompetent but
http://jmm.sgmjournals.org
OR
95 % CI
1.0
6.04
2.88
11.27
4.38–8.34
2.07–4.01
7.67–16.58
1.0
6.11
2.31
8.34
4.45–8.40
1.68–3.18
5.64–12.32
1.0
2.68
2.17
4.11
1.93–3.73
1.57–3.00
2.91–5.82
1.0
0.25
0.17–0.39
1.0
0.35
0.24–0.50
1.0
0.26
0.17–0.38
not infected with human immunodeficiency virus
(McNally et al., 2006).
In addition, antimicrobial drugs or vaccines that target
specific bacterial species may alter microbial communities in the URT, with unanticipated consequences. There
is debate about the effects of pneumococcal vaccination
on the colonization and infection by other respiratory
bacteria. van Gils et al. (2011) showed a temporary
increase in Staph. aureus colonization in children at
around 12 months of age after the PCV7 vaccination. In
addition, it has been reported that the use of PCV7
increased Staph. aureus-related acute otitis media
(Veenhoven et al., 2003). However, some studies have
found no increase in Staph. aureus acute otitis media
associated with the PCV7 vaccine (Casey et al., 2010;
Cohen et al., 2007). This trend was observed for the
proportion of bacteraemia caused by Staph. aureus in
young children after vaccination (Herz et al., 2006).
Considering our results, these previous results support
the suggestion that nasopharynx flora modification such
as the elimination of Strep. pneumoniae, H. influenzae
and M. catarrhalis may increase the likelihood of Staph.
aureus colonization and the risk of Staph. aureus
infection.
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683
S. Bae and others
Recent approaches in the development and use of vaccines
to reduce the carriage of potential respiratory pathogens
may have an influence on the prevalence of URT colonization by target bacteria and the incidence of subsequent respiratory infection. Thus, an understanding of
the interaction between bacteria may be important for
predicting changes in the ecology of URTs and for
designing control strategies that target bacterial colonization in the URT.
Herz, A. M., Greenhow, T. L., Alcantara, J., Hansen, J., Baxter, R. P.,
Black, S. B. & Shinefield, H. R. (2006). Changing epidemiology of
outpatient bacteremia in 3- to 36-month-old children after the
introduction of the heptavalent-conjugated pneumococcal vaccine.
Pediatr Infect Dis J 25, 293–300.
Jacobs, M. R., Felmingham, D., Appelbaum, P. C., Grüneberg, R. N. &
Alexander Project Group (2003). The Alexander Project 1998–2000:
susceptibility of pathogens isolated from community-acquired
respiratory tract infection to commonly used antimicrobial agents.
J Antimicrob Chemother 52, 229–246.
Jacoby, P., Watson, K., Bowman, J., Taylor, A., Riley, T. V.,
Smith, D. W. & Lehmann, D. on behalf of the Kalgoorlie Otitis
Media Research Project Team (2007). Modelling the co-
ACKNOWLEDGEMENTS
We are grateful to all those who collaborated in this study: the
directors, staff, children and their parents of the three kindergartens
and the elementary school in Seoul, Korea. This work was supported
by a grant from the National Institute of Health, Korea Centers for
Disease Control and Prevention.
occurrence of Streptococcus pneumoniae with other bacterial and
viral pathogens in the upper respiratory tract. Vaccine 25, 2458–
2464.
Korean Ministry of Health & Welfare (2010). 2010 Yearbook of Health
and Welfare Statistics, vol. 56. Korea: Korean Ministry of Health &
Welfare.
Marchisio, P., Gironi, S., Esposito, S., Schito, G. C., Mannelli, S.,
Principi, N. & Ascanius Project Collaborative Group (2001).
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