Journal of Medical Microbiology Papers in Press. Published January 22, 2015 as doi:10.1099/jmm.0.000029
Journal of Medical Microbiology STREPTOCOCCUS PNEUMONIAE AND STAPHYLOCOCCUS AUREUS CARRIAGE IN HEALTHY SCHOOL-AGE CHILDREN AND ADOLESCENTS --Manuscript Draft-Manuscript Number:
JMM-D-14-00271R1
Full Title:
STREPTOCOCCUS PNEUMONIAE AND STAPHYLOCOCCUS AUREUS CARRIAGE IN HEALTHY SCHOOL-AGE CHILDREN AND ADOLESCENTS
Short Title:
Streptococcus pneumoniae and Staphylococcus aureus
Article Type:
Standard
Section/Category:
Epidemiology
Corresponding Author:
Susanna Esposito Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan Milan, ITALY
First Author:
Susanna Esposito
Order of Authors:
Susanna Esposito Leonardo Terranova Luca Ruggiero Beatrice Ascolese Valentina Montinaro Walter Peves Rios Carlotta Galeone Nicola Principi
Abstract:
Streptococcus pneumoniae and Staphylococcus aureus are common commensals of the upper respiratory tract in children and adolescents. Understanding the relationship between these two pathogens, including their potential for mutual interference, is needed to evaluate their epidemiological status as well as the impact of related preventative measures. We obtained oropharyngeal and nasal swabs from 497 healthy subjects aged 6 to 17 years. S. pneumoniae detection and serotyping were performed using a real-time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE MRSA system. We found that 136 (27.3%) of the children were carriers of both pathogens, 121 (24.3%) of the children carried S. pneumoniae alone, and 128 (25.7%) of the children carried S. aureus alone. S. aureus carriage was similar between children who did vs. did not carry S. pneumoniae and was independent of age and vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) also did not affect S. aureus carriage. Pneumococcal serotype also did not appear to affect S. aureus carriage. These findings suggest that the carriage of S. pneumoniae does not affect that of S. aureus in older children and adolescents, regardless of age, PCV7 vaccination, and pneumococcal serotype.
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Manuscript Including References (Word document) Click here to download Manuscript Including References (Word document): Esposito manuscript.docx
1
STREPTOCOCCUS PNEUMONIAE AND STAPHYLOCOCCUS AUREUS CARRIAGE IN
2
HEALTHY SCHOOL-AGE CHILDREN AND ADOLESCENTS
3
Susanna Esposito1, Leonardo Terranova1, Luca Ruggiero1, Beatrice Ascolese1, Valentina
4
Montinaro1, Walter Peves Rios1, Carlotta Galeone2, Nicola Principi1
5 6
1
7
Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
8
Milan, Italy; 2Department of Clinical Sciences and Community Health, Università degli Studi di
9
Milano, Milan, Italy
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation,
10 11
Running title: Streptococcus pneumoniae and Staphylococcus aureus.
12
Contents category: Epidemiology.
13 14
Correspondence and requests for reprints should be addressed to:
15
Susanna Esposito
16
Pediatric Highly Intensive Care Unit
17
Department of Pathophysiology and Transplantation
18
Università degli Studi di Milano
19
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
20
Via Commenda 9
21
20122 Milano, Italy.
22
Tel.: +39-02-55032498; Fax: +39-02-50320206.
23
E-mail: [email protected]
24
1
25
ABSTRACT
26
Streptococcus pneumoniae and Staphylococcus aureus are common commensals of the upper
27
respiratory tract in children and adolescents. Understanding the relationship between these two
28
pathogens, including their potential for mutual interference, is needed to evaluate the epidemiology
29
of the diseases they cause, the factors that condition acquisition and carriage, and the impact of
30
related preventative measures. We obtained oropharyngeal and nasal swabs from 497 healthy
31
subjects aged 6 to 17 years. S. pneumoniae detection and serotyping were performed using a real-
32
time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE
33
MRSA system. We found that 136 (27.3 %) of the children were carriers of both species, 121 (24.3
34
%) of the children carried S. pneumoniae alone, and 128 (25.7 %) of the children carried S. aureus
35
alone. S. aureus carriage was similar between children who carried S. pneumoniae (136/257, 52.9
36
%, 95 % confidence interval [CI]: 46.8 % - 58.9 %) vs. those who did not (128/240, 53.3 %, 95 %
37
CI: 47.0 % - 59.5 % ) and was independent of age and vaccination with 7-valent pneumococcal
38
conjugate vaccine (PCV7). Vaccination with PCV7 did not affect S. aureus carriage (S.
39
pneumoniae: 84/143 (58.7 %, 95 % CI: 50.5 % - 66.5 %) vaccinated children vs 171/351 (48.7 %,
40
95 % CI: 43.5 % - 53.9 %) unvaccinated children; S. aureus: 67/143 (46.9 %, 95 % CI: 38.9 % -
41
55.0 %) vaccinated children vs 195/351 (55.6 %, 95 % CI: 50.3 % - 60.7 %) unvaccinated children).
42
Pneumococcal serotype also did not appear to affect S. aureus carriage. These findings suggest that
43
the carriage of S. pneumoniae does not affect that of S. aureus in older children and adolescents,
44
regardless of age, PCV7 vaccination, and pneumococcal serotype.
45 46
Key words: carrier status; nasopharyngeal carriage; Staphylococcus aureus; Streptococcus
47
pneumoniae; 7-valent pneumococcal conjugate vaccine; 13-valent pneumococcal conjugate
48
vaccine.
49 2
50
INTRODUCTION
51
Streptococcus pneumoniae and Staphylococcus aureus are common commensals of the upper
52
respiratory tract in children (Simell et al., 2012; Wertheim et al., 2005). Understanding the
53
relationship between these two pathogens, including their potential for mutual interference, is
54
needed to evaluate the epidemiology of the diseases they cause, the factors that condition
55
acquisition and carriage as well as the impact of related preventative measures, such as
56
pneumococcal conjugate vaccines. Several studies have investigated the co-colonization of both
57
healthy and ill children by S. pneumoniae and S. aureus but have reported conflicting results
58
(Cohen et al., 2007; McNally et al., 2006; Quintero et al., 2011; Regev-Yochay et al., 2004). In
59
general, in healthy subjects pneumococcal colonization seems to negatively influence S. aureus
60
carriage, whereas in children with disease, particularly when associated with severe
61
immunodeficiency, this relationship is no more evident. However, several factors other than host
62
immune characteristics can influence carriage and relationships among bacteria that colonize the
63
pharynx. It has been demonstrated that S. pneumoniae carriage is higher in younger patients and
64
declines with age (Le Polain de Waroux et al., 2014; Kluytmans et al., 1997), while S. aureus
65
carriage has two major peaks, one in early infancy and one in older children (Kwambana et al.
66
2011). Moreover, number of siblings, passive smoking, school attendance and socioeconomic
67
characteristics of the family play a role at this regard (Simell et al., 2012). Finally, administration
68
of pneumococcal conjugate vaccines (PCVs) to infants significantly modifies pneumococcal
69
carriage of vaccinated and unvaccinated infants and toddlers and in some even if not in all of the
70
studies has been demonstrated able to influence S. aureus carriage of these subjects. (Dukers-
71
Muijrers et al., 2013; Bogaert et al., 2004; Xu et al., 2012).
72
However, most of the studies that evaluated bacteria flora pharyngeal carriage and relationships
73
between S. pneumoniae and S. aureus were carried out in younger children and little is known on
74
the characteristics of carriage of these pathogens in school-age children and adolescents. Moreover, 3
75
no data are available on the impact of PCVs, given several years before, on S. pneumoniae and S.
76
aureus colonization of these subjects. Finally, it is not known whether the pharyngeal site where
77
respiratory secretions used to evaluate carriage are collected can influence final results. Usually, S.
78
pneumoniae colonization is identified with nasopharyngeal swab (i.e., the swab is obtained gently
79
passing through a nostril and collecting the specimen into the nasopharynx that is the part of the
80
pharynx covering the roof of the mouth), whereas anterior nares sample collecting the specimen
81
from the nostrils is used for S. aureus evaluation. However, recent studies seem to suggest that
82
oropharyngeal sample is better for determining S. pneumoniae carrier status in school-age children
83
and adolescents (Principi et al., 2014) and may increase S. aureus identification when coupled with
84
traditional anterior nares samples (Mertz et al., 2009). In order to increase our knowledge to these
85
unsolved problems, a study to evaluate S. pneumoniae and S. aureus naso- and oropharyngeal
86
colonization in a group of school-age children and adolescents partly vaccinated during infancy
87
with the heptavalent pneumococcal conjugate vaccine (PCV7) was planned.
88 89
METHODS
90
Swab collection
91
The study enrolled healthy children and adolescents (ages 6 to 17 years) attending mandatory
92
school in Milan (Italy) during the second and third week of December 2013. Subjects who received
93
antibiotics 3 weeks prior to sampling were excluded from the study. Data regarding medical history
94
of each subject including vaccination were collected by means of a questionnaire that was
95
completed by parents/guardians for children
Journal of Medical Microbiology STREPTOCOCCUS PNEUMONIAE AND STAPHYLOCOCCUS AUREUS CARRIAGE IN HEALTHY SCHOOL-AGE CHILDREN AND ADOLESCENTS --Manuscript Draft-Manuscript Number:
JMM-D-14-00271R1
Full Title:
STREPTOCOCCUS PNEUMONIAE AND STAPHYLOCOCCUS AUREUS CARRIAGE IN HEALTHY SCHOOL-AGE CHILDREN AND ADOLESCENTS
Short Title:
Streptococcus pneumoniae and Staphylococcus aureus
Article Type:
Standard
Section/Category:
Epidemiology
Corresponding Author:
Susanna Esposito Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan Milan, ITALY
First Author:
Susanna Esposito
Order of Authors:
Susanna Esposito Leonardo Terranova Luca Ruggiero Beatrice Ascolese Valentina Montinaro Walter Peves Rios Carlotta Galeone Nicola Principi
Abstract:
Streptococcus pneumoniae and Staphylococcus aureus are common commensals of the upper respiratory tract in children and adolescents. Understanding the relationship between these two pathogens, including their potential for mutual interference, is needed to evaluate their epidemiological status as well as the impact of related preventative measures. We obtained oropharyngeal and nasal swabs from 497 healthy subjects aged 6 to 17 years. S. pneumoniae detection and serotyping were performed using a real-time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE MRSA system. We found that 136 (27.3%) of the children were carriers of both pathogens, 121 (24.3%) of the children carried S. pneumoniae alone, and 128 (25.7%) of the children carried S. aureus alone. S. aureus carriage was similar between children who did vs. did not carry S. pneumoniae and was independent of age and vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) also did not affect S. aureus carriage. Pneumococcal serotype also did not appear to affect S. aureus carriage. These findings suggest that the carriage of S. pneumoniae does not affect that of S. aureus in older children and adolescents, regardless of age, PCV7 vaccination, and pneumococcal serotype.
Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation
Manuscript Including References (Word document) Click here to download Manuscript Including References (Word document): Esposito manuscript.docx
1
STREPTOCOCCUS PNEUMONIAE AND STAPHYLOCOCCUS AUREUS CARRIAGE IN
2
HEALTHY SCHOOL-AGE CHILDREN AND ADOLESCENTS
3
Susanna Esposito1, Leonardo Terranova1, Luca Ruggiero1, Beatrice Ascolese1, Valentina
4
Montinaro1, Walter Peves Rios1, Carlotta Galeone2, Nicola Principi1
5 6
1
7
Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
8
Milan, Italy; 2Department of Clinical Sciences and Community Health, Università degli Studi di
9
Milano, Milan, Italy
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation,
10 11
Running title: Streptococcus pneumoniae and Staphylococcus aureus.
12
Contents category: Epidemiology.
13 14
Correspondence and requests for reprints should be addressed to:
15
Susanna Esposito
16
Pediatric Highly Intensive Care Unit
17
Department of Pathophysiology and Transplantation
18
Università degli Studi di Milano
19
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
20
Via Commenda 9
21
20122 Milano, Italy.
22
Tel.: +39-02-55032498; Fax: +39-02-50320206.
23
E-mail: [email protected]
24
1
25
ABSTRACT
26
Streptococcus pneumoniae and Staphylococcus aureus are common commensals of the upper
27
respiratory tract in children and adolescents. Understanding the relationship between these two
28
pathogens, including their potential for mutual interference, is needed to evaluate the epidemiology
29
of the diseases they cause, the factors that condition acquisition and carriage, and the impact of
30
related preventative measures. We obtained oropharyngeal and nasal swabs from 497 healthy
31
subjects aged 6 to 17 years. S. pneumoniae detection and serotyping were performed using a real-
32
time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE
33
MRSA system. We found that 136 (27.3 %) of the children were carriers of both species, 121 (24.3
34
%) of the children carried S. pneumoniae alone, and 128 (25.7 %) of the children carried S. aureus
35
alone. S. aureus carriage was similar between children who carried S. pneumoniae (136/257, 52.9
36
%, 95 % confidence interval [CI]: 46.8 % - 58.9 %) vs. those who did not (128/240, 53.3 %, 95 %
37
CI: 47.0 % - 59.5 % ) and was independent of age and vaccination with 7-valent pneumococcal
38
conjugate vaccine (PCV7). Vaccination with PCV7 did not affect S. aureus carriage (S.
39
pneumoniae: 84/143 (58.7 %, 95 % CI: 50.5 % - 66.5 %) vaccinated children vs 171/351 (48.7 %,
40
95 % CI: 43.5 % - 53.9 %) unvaccinated children; S. aureus: 67/143 (46.9 %, 95 % CI: 38.9 % -
41
55.0 %) vaccinated children vs 195/351 (55.6 %, 95 % CI: 50.3 % - 60.7 %) unvaccinated children).
42
Pneumococcal serotype also did not appear to affect S. aureus carriage. These findings suggest that
43
the carriage of S. pneumoniae does not affect that of S. aureus in older children and adolescents,
44
regardless of age, PCV7 vaccination, and pneumococcal serotype.
45 46
Key words: carrier status; nasopharyngeal carriage; Staphylococcus aureus; Streptococcus
47
pneumoniae; 7-valent pneumococcal conjugate vaccine; 13-valent pneumococcal conjugate
48
vaccine.
49 2
50
INTRODUCTION
51
Streptococcus pneumoniae and Staphylococcus aureus are common commensals of the upper
52
respiratory tract in children (Simell et al., 2012; Wertheim et al., 2005). Understanding the
53
relationship between these two pathogens, including their potential for mutual interference, is
54
needed to evaluate the epidemiology of the diseases they cause, the factors that condition
55
acquisition and carriage as well as the impact of related preventative measures, such as
56
pneumococcal conjugate vaccines. Several studies have investigated the co-colonization of both
57
healthy and ill children by S. pneumoniae and S. aureus but have reported conflicting results
58
(Cohen et al., 2007; McNally et al., 2006; Quintero et al., 2011; Regev-Yochay et al., 2004). In
59
general, in healthy subjects pneumococcal colonization seems to negatively influence S. aureus
60
carriage, whereas in children with disease, particularly when associated with severe
61
immunodeficiency, this relationship is no more evident. However, several factors other than host
62
immune characteristics can influence carriage and relationships among bacteria that colonize the
63
pharynx. It has been demonstrated that S. pneumoniae carriage is higher in younger patients and
64
declines with age (Le Polain de Waroux et al., 2014; Kluytmans et al., 1997), while S. aureus
65
carriage has two major peaks, one in early infancy and one in older children (Kwambana et al.
66
2011). Moreover, number of siblings, passive smoking, school attendance and socioeconomic
67
characteristics of the family play a role at this regard (Simell et al., 2012). Finally, administration
68
of pneumococcal conjugate vaccines (PCVs) to infants significantly modifies pneumococcal
69
carriage of vaccinated and unvaccinated infants and toddlers and in some even if not in all of the
70
studies has been demonstrated able to influence S. aureus carriage of these subjects. (Dukers-
71
Muijrers et al., 2013; Bogaert et al., 2004; Xu et al., 2012).
72
However, most of the studies that evaluated bacteria flora pharyngeal carriage and relationships
73
between S. pneumoniae and S. aureus were carried out in younger children and little is known on
74
the characteristics of carriage of these pathogens in school-age children and adolescents. Moreover, 3
75
no data are available on the impact of PCVs, given several years before, on S. pneumoniae and S.
76
aureus colonization of these subjects. Finally, it is not known whether the pharyngeal site where
77
respiratory secretions used to evaluate carriage are collected can influence final results. Usually, S.
78
pneumoniae colonization is identified with nasopharyngeal swab (i.e., the swab is obtained gently
79
passing through a nostril and collecting the specimen into the nasopharynx that is the part of the
80
pharynx covering the roof of the mouth), whereas anterior nares sample collecting the specimen
81
from the nostrils is used for S. aureus evaluation. However, recent studies seem to suggest that
82
oropharyngeal sample is better for determining S. pneumoniae carrier status in school-age children
83
and adolescents (Principi et al., 2014) and may increase S. aureus identification when coupled with
84
traditional anterior nares samples (Mertz et al., 2009). In order to increase our knowledge to these
85
unsolved problems, a study to evaluate S. pneumoniae and S. aureus naso- and oropharyngeal
86
colonization in a group of school-age children and adolescents partly vaccinated during infancy
87
with the heptavalent pneumococcal conjugate vaccine (PCV7) was planned.
88 89
METHODS
90
Swab collection
91
The study enrolled healthy children and adolescents (ages 6 to 17 years) attending mandatory
92
school in Milan (Italy) during the second and third week of December 2013. Subjects who received
93
antibiotics 3 weeks prior to sampling were excluded from the study. Data regarding medical history
94
of each subject including vaccination were collected by means of a questionnaire that was
95
completed by parents/guardians for children
