Predictors of pneumococcal carriage and the effect of the 13-valent pneumococcal conjugate vaccination in the Western Australian Aboriginal population
Collins et al. Pneumonia
Predictors of pneumococcal carriage and the effect of the 13-valent pneumococcal conjugate vaccination in the Western Australian Aboriginal population
Deirdre A. Collins 0 1
Anke Hoskins 0
Thomas Snelling 0
Kalpani Senasinghe 0
Jacinta Bowman 2
Natalie A. Stemberger 2
Amanda J. Leach 3
Deborah Lehmann 0
0 Wesfarmers Centre of Vaccines & Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, WA , Australia
1 School of Medical and Health Sciences, Edith Cowan University , Perth, WA , Australia
2 Division of Microbiology & Infectious Diseases, PathWest Laboratory Medicine WA , Perth, WA , Australia
3 Menzies School of Health Research, Charles Darwin University , Darwin, Northern Territory , Australia
Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to prevent invasive pneumococcal disease (IPD) in Western Australian (WA) Aboriginal people in 2001. PCV13 replaced PCV7 in July 2011, covering six additional pneumococcal serotypes; however, IPD rates remained high in Aboriginal people in WA. Upper respiratory tract pneumococcal carriage can precede IPD, and PCVs alter serotype distribution. Methods: To assess the impact of PCV13 introduction, identify emerging serotypes, and assess risk factors for carriage, nasopharyngeal swabs and information on demographic characteristics, health, medication and living conditions from Aboriginal children and adults across WA from August 2008 to November 2014 were collected. Bacteria were cultured using selective media and pneumococcal isolates were serotyped by Quellung reaction. Risk factors were analysed by multivariable logistic regression. Results: One thousand five hundred swabs pre- and 1385 swabs post-PCV13 introduction were collected. Pneumococcal carriage was detected in 66.8% of children <5 years old and 53.2% of 5-14 year-olds post-PCV13, compared with prePCV13 prevalence of 72.2% and 49.4%, respectively. The prevalence of PCV13-non-PCV7 serotypes decreased in children <5 years old from 13.5% pre-PCV13 to 5.8% post-PCV13 (p < 0.01), and from 8.4% to 6.1% in children 5-14 years old (p > 0.05). The most common serotypes post-PCV13 were 11A (prevalence 4.0%), 15B (3.5%), 16F (3.5%), and 19F (3.2%). Risk of detection of pneumococcal carriage increased until age 12 months (odds ratio [OR] 4.19, 95% confidence interval [CI] 2.39-7.33), with nasal discharge (OR 2.49 [95% CI 2.00-3.09]), residence in a remote community (OR 2.21 [95% CI 1.672.92]) and household crowding (OR 1.36 [95% CI 1.11-1.67]). Recent antibiotic use was negatively associated with pneumococcal carriage (OR 0.48 [95% CI 0.33-0.69]). Complete resistance to penicillin was present among isolates of serotypes 19A (6.0%), 19F (2.3%) and non-serotypeable isolates (1.9%). Serotype 23F and newly emerged serotype 7B isolates showed high rates of resistance to cotrimoxazole, erythromycin and tetracycline (86.9%, 86.9%, 82.0%, respectively for 23F, 100.0%, 100.0% and 93.3% for 7B). Conclusion: Since PCV13 replaced PCV7, carriage of PCV13-non-PCV7 serotypes decreased significantly among children <5 years old, those most likely to have received PCV13, and to a lesser extent in older people. Known risk factors for carriage including crowding and young age remain in the Aboriginal population.
Streptococcus pneumoniae; Colonization; Pneumococcal disease; Aboriginal; Vaccination; Australia; PCV13
Streptococcus pneumoniae is estimated to cause up to a
million deaths from invasive pneumococcal disease
(IPD) per year, worldwide [
]. While the greatest burden
of IPD is concentrated in resource-poor countries,
Australian Aboriginal people in central and western
regions of Australia experience an almost five-fold greater
incidence of IPD than non-Aboriginal Australians [
addition to high rates of IPD, Aboriginal children also
experience a high burden of other manifestations of
pneumococcal disease, including pneumonia and otitis
media (OM) [
Vaccination to prevent IPD is effective against targeted
serotypes, but limited by the existence of at least 93
serotypes of S. pneumoniae, each differentiated by its
polysaccharide capsule. The 7-valent pneumococcal
conjugate vaccine (PCV7, covering serotypes 4, 6B, 9V, 14,
18C, 19F and 23F) was introduced for Australian
Aboriginal children at 2, 4 and 6 months old in 2001 with a
booster dose of 23-valent pneumococcal polysaccharide
vaccine (23vPPV, covering PCV7 serotypes and 1, 2, 3, 5,
7F, 8, 9 N, 10A, 11A, 12F, 15B, 17F, 19A, 20, 22F, and
23F) scheduled at 18 months old. A catch-up schedule
was in place for children <2 years old and for children
<5 years old with predisposing medical conditions. All
Australian children became eligible in 2005 for 3
primary doses of PCV7 with no scheduled booster.
Following the introduction of PCV7, IPD rates initially fell in
the Aboriginal population in Western Australia (WA)
but subsequently increased in adults [
]. The observed
increase was accompanied by a rise in IPD caused by
non-PCV7 serotypes [
On 1 July 2011, PCV7 was recalled and immediately
replaced with PCV13 (covering the six additional
serotypes 1, 3, 5, 6A, 7F and 19A). For Aboriginal children, a
fourth dose of PCV13 at 18 months old replaced the
23vPPV booster over a transition period from September
2011 to October 2012 [
]. Following PCV13
introduction in Australia, IPD rates appeared to decrease;
however, rates in IPD caused by non-PCV13 serotypes
Nasopharyngeal carriage of S. pneumoniae is generally
asymptomatic but is an important precursor to
pneumococcal disease. Pneumococcal carriage studies have been
used to monitor the prevalence and distribution of S.
pneumoniae serotypes in WA, and for surveillance of
antibiotic resistant strains. Despite introduction of the
PCV program, pneumococcal carriage rates remain high
among Aboriginal people [
], and have been observed
to be higher in Aboriginal children than in
nonAboriginal children . In WA, carriage rates were
71.9% and 34.6% among Aboriginal children <5 years
old and people ≥5 years old, respectively, after
introduction of PCV7 [
]. Most pneumococcal carriage serotypes
in WA in the PCV7 era were non-PCV7 serotypes, the
most common being 19A, 16F and 6C [
Given that the PCV vaccination program does not
appear to have reduced overall IPD rates in the Aboriginal
population in age groups other than children <5 years
], it is important to identify risk factors for carriage of
S. pneumoniae to help identify further opportunities for
prevention of pneumococcal disease. Previously,
household crowding and exposure to environmental tobacco
smoke (ETS) have been identified as risk factors [
The authors have monitored pneumococcal carriage in
Aboriginal people living in WA since 2008. This study
describes the prevalence of overall carriage and that of
individual serotypes in the WA Aboriginal population
before and after the introduction of PCV13, along with
epidemiological risk factors for carriage.
Aboriginal people make up about 3% of the total WA
population (total 2.2 million people); 39% live in the
Perth metropolitan area, the remainder in regional
towns or scattered sparsely across remote areas of
WA. The WA climate varies, from tropical in the
north to inland deserts and warm temperate
southwest coastal regions.
Sample and data collection and laboratory analysis
The surveillance study has been described previously [
In brief, nasopharyngeal swabs or nose blown samples
] were collected opportunistically from Aboriginal
people of all ages in communities across WA from
August 2008 to November 2014. Participants were
defined as having participated “pre-PCV13” introduction
(from study start until 30 June 2011) or “post-PCV13”
(from 1 July 2011 onwards). Demographic,
environmental and health data including details on smoking
behaviour and exposure, numbers of co-resident household
members, recent medication and illness were collected by
completing a questionnaire during face-to-face interviews.
Swabs were cultured on selective media. S. pneumoniae
isolates were confirmed by optochin susceptibility. Two
pneumococcal isolates (or more, if morphologically
distinct) per positive culture were subcultured and serotyped
by the Quellung reaction using antisera from the Statens
Serum Institut, Denmark [
]. Isolates that could not be
serotyped by Quellung reaction were referred to as
“nonserotypeable”. Antimicrobial susceptibilities were tested by
disc diffusion. E-test (bioMérieux Diagnostics, France)
was performed where reduced antimicrobial
susceptibility was determined by disc diffusion. Resistance to
antimicrobials was classified according to the Clinical
and Laboratory Standards Institute guidelines [
Breakpoints for intermediate and complete resistance
to penicillin (collectively termed “non-susceptibility”)
were 4 μg/mL and 8 μg/mL, respectively.
The remoteness (metropolitan, regional or remote) of
communities was classified using the Australian
Statistical Geography Standard Remoteness Structure [
Household crowding was defined as ≥5 people sharing
accommodation on the night prior to sample collection.
Co-residence with a child was defined as sharing with at
least one child <5 years old on the previous night.
Respiratory symptoms were defined as any cough, sore
throat, or blocked or runny nose as reported by the
participant or guardian. Environmental tobacco smoke
(ETS) exposure was considered present if it was reported
that any co-resident was a smoker. The immunization
status of children was determined from the Australian
Childhood Immunization Register (ACIR), accessed
using the participant’s name and date of birth. Children
were classified as vaccinated with PCV7 or PCV13 if
they had received at least two doses of the relevant
vaccine at least 2 weeks prior to specimen collection.
All descriptive and statistical analyses were performed
using SPSS v22.0 (IBM Corp., Armonk, New York,
United States of America [USA]) and Stata 11 (Stata
Corporation, College Station, Texas, USA). Results of
culture and serotyping were aggregated according to
serotype to calculate the prevalence of individual
serotypes among all study participants. Differences in crude
proportions were compared using χ2 test; statistical
significance was considered if p < 0.05. A multivariable
logistic regression model was used to identify
independent risk factors for carriage of serotypeable
pneumococci. Variables were included, if identified previously in
the literature as risk factors for carriage, in a backwards
stepwise model, eliminating variables using a cut-off
value of p > 0.05. Vaccination status was excluded from
the risk factor analysis due to poor recovery of
vaccination records and low number of PCV13-vaccinated
children (see Results section). The influence of age on
carriage risk was modelled using a spline function with
knots at age 1 year and at 20 years, based on previous
findings of a peak in carriage at 12 months of age in this
particular population [
]. The influence of calendar time
was modelled as a linear continuous variable, with
the influence of the PCV13 program on carriage
explored using a simple marginal spline function with a
single knot corresponding to 1 July 2011, the date of
Approval was granted by the Princess Margaret Hospital
for Children Ethics Committee, the Western Australian
Country Health Service Board Research Ethics Committee
and the Western Australian Aboriginal Health Ethics
Committee. Approval to approach communities in the
Kimberley region was granted by the Kimberley Aboriginal
Health Planning Forum. Consent was sought from
adult participants and from the parents or guardians
of child participants.
In total 2885 nasopharyngeal samples (2824
nasopharyngeal swabs; 60 nose blown samples; 1 unknown) were
collected: 1500 before the introduction of PCV13 on 1
July 2011, and 1385 afterwards. Most participants
reported being healthy on the day of participation, while
31.5% had visible nasal discharge and 8.4% reported
respiratory symptoms (Table 1). Most samples were
collected among remote residents (78.2%). Crowding
(61.7%) and co-residence with children (73.5%) were
common across all age groups. Any ETS exposure was
reported by 65.3% of participants; 22.9% reported
exposure to indoor ETS, and 55.6% of adult respondents
reported smoking themselves. Recent antibiotic use was
reported by 7.6% of participants. Immunization status
could be determined for only 628 (59.1%) participants
<5 years old and 488 (51.5%) participants 5–14 years old.
Among PCV7 age-eligible children whose immunization
status was available, 504 (89.4%) of those <5 years old and
302 (74.6%) of those aged 5–14 years were vaccinated with
PCV7 (Table 1). Among children eligible for PCV13
whose immunization status was known, 37 (59.7%) were
vaccinated with at least two doses of PCV13 and 64
(98.5%) had received at least one dose. A combination of
PCV7 and PCV13 (at least one dose of each) was received
by 66 (6.8%) children.
Compared to the pre-PCV13 period, carriage of any
pneumococcal serotype was less common in the
post-PCV13 period among adults (19.5% versus 9.9%,
p < 0.01) and to a lesser extent among children <5 years
old (72.2% versus 66.8%, p = 0.054) but not in children
5–14 years old (49.4% versus 53.2%, p = 0.24). Carriage
of PCV13-non-PCV7 serotypes was less common
postPCV13 introduction among children <5 years old (13.5%
versus 5.8%, p < 0.01; Table 1, Fig. 1). There was also a
numerical reduction in carriage of vaccine serotypes in
older age groups (Table 1). S. pneumoniae was recovered
from 46.8% of nasopharyngeal swabs and 56.7% of
Culture identified 1357 pneumococcus-positive
specimens (47.0%) giving 1590 distinct pneumococcal
isolates, 1374 (86.4%) of which were serotypeable (Table 2).
The most common of the 48 serotypes detected were
16F (prevalence 3.8%), 6C (3.6%), 11A (3.3%), 19F (3.0%),
Denominators for proportions varied due to missing data. Proportions were compared using χ2
*p < 0.05, **p < 0.01
aTwo participants carried a PCV7 and PCV13-non-PCV7 serotype simultaneously
bOne participant carried a PCV7 and PCV13-non-PCV7 serotype simultaneously
cDenominator is number of participants at time of enrolment pre/post PCV13. Includes participants vaccinated with PCV7 prior to introduction of PCV13
19A (2.9%) and 15B (2.6%). Several PCV13 serotypes
decreased in frequency post-PCV13 introduction in
children <5 years old: PCV7 type 23F (4.8% versus
1.8%, p < 0.05), PCV13-non-PCV7 types 6A (3.6%
versus 1.4%, p < 0.05) and 19A (7.7% versus 3.2%,
p < 0.05) (Fig. 2). Reductions in PCV13 types were
also observed in participants ≥5 years old, to a lesser
extent than that seen in children <5 years (15.5% to
12.1% in 5–14 years, p = 0.12; 4.1% to 2.2% in ≥15
years group, p = 0.10, Table 1).
Carriage of more than one serotype was identified in
131 (4.5%) specimens. Non-serotypeable isolates were
detected in addition to a serotypeable isolate in 81
(2.8%) specimens. The prevalence of a non-serotypeable
pneumococcus in the absence of serotypeable strains
was lower post-PCV13 (4.7% versus 3.9%, p = 0.06).
Among 36 non-PCV13 serotypes identified, the
prevalence of 11A (4.8% versus 8.4%, p < 0.05), 15B (2.1%
versus 7.0%, p < 0.01) and 21 (0.9% versus 2.6%, p < 0.05)
increased significantly among children <5 years old while
7B and 29 were only detected post-PCV13 (2.0% and
1.8% respectively, both p < 0.05). Serotypes 6C and 23B
were detected less frequently post-PCV13 introduction
in children <5 years old (8.0% versus 3.4%, p < 0.05 and
5.0% versus 1.8%, p < 0.05; Fig. 2).
Non-susceptibility to penicillin was present in 25.2% of
isolates, including in 84.9% of serotype 19F isolates. Complete
resistance to penicillin was uncommon, found among
isolates of serotypes 19A (6.0%), 19F (2.3%) and
nonserotypeable isolates (1.9%) only (Table 2). Serotype 23F
isolates showed high rates of resistance to cotrimoxazole,
erythromycin and tetracycline (86.9%, 86.9% and 82.0%,
respectively). Multi-resistance to three or more antibiotics
was recorded in 102 serotypeable isolates (7.4%) overall;
mainly serotype 15A isolates (68.0%) and serotype 23F
isolates (88.5%). Isolates of serotype 7B (n = 15), which were
only detected post-PCV13, were all resistant to
cotrimoxazole and erythromycin, non-susceptible to penicillin and
93.3% were resistant to tetracycline (Table 2). Overall,
susceptibility of strains to antimicrobials did not change
significantly after introduction of PCV13, apart from a
decrease in cotrimoxazole resistance (26.1% to 21.3%,
p < 0.05, Table 2). Multi-resistance was present in 17.6% of
48 serotypes were identified among 1374 serotypeable isolates, 216 isolates were non-serotypeable (NT)
Cotr cotrimoxazole, ery erythromycin, tet tetracycline, pen penicillin; R resistant, I intermediate resistance
*p < 0.05
Risk factors for pneumococcal carriage
Carriage of any serotypeable pneumococcus was more
common among males (OR 1.56 [95% CI 1.35–1.81])
and those who were carriers of Haemophilus influenzae
(OR 10.29 [95% CI 8.60–12.30]) and Moraxella
catarrhalis (OR 7.10 [95% CI 6.01–8.39]) compared with
those who were not (Table 3). Pneumococcal carriage
was detected more commonly among those reporting
respiratory symptoms (OR 1.48 [95% CI 1.14–1.94]), in
the presence of nasal discharge (OR 4.84 [95% CI 4.01–
5.74]), among those living in a remote community (OR
1.86 [95% CI 1.41–2.35]) and those living in crowded
households (OR 1.35 [95% CI 1.15–1.58]). Pneumococcal
carriage was detected less commonly among those who
reported recent antibiotic use (OR 0.73 [95% CI
0.55–0.98]) and in Staphylococcus aureus carriers (OR
0.56 [95% CI 0.44–0.72]) than among those who were
not (Table 3).
In the multivariable analysis, significant independent
predictors of carriage of any serotypeable pneumococcus
included the presence of nasal discharge (OR 2.49 [95%
CI 2.00–3.09]), crowding (OR 1.36 [95% CI 1.11–1.67])
and remote versus urban residence (OR 2.21 [95% CI
1.67–2.92]). Recent receipt of antibiotics was associated
with lower odds of detection of pneumococcal carriage
(OR 0.48 [95% CI 0.33–0.69]). After modelling for the
influence of age using the spline function, there was a
significant risk of carriage of pneumococcus up to age
1 year (OR 4.19 [95% CI 2.39–7.33]), which then
decreased from 1 year to 19 years (14.7% decline per
year; OR 0.85 [95% CI 12.9–16.4], Table 3). Adjusting
for other factors, there was no evidence that
introduction of PCV13 was associated with an overall reduction
in all pneumococcal serotypes (Fig. 1).
The overall prevalence of carriage of pneumococci
among WA Aboriginal children and adults remains high
following the introduction of PCV13. For children,
pneumococcal carriage has remained relatively stable
over time, with carriage increasing in infants until
around their first birthday and then slowly declining
with increasing age to adulthood (Table 3).
IPD rates caused by non-PCV serotypes have increased
since the introduction of PCV13 nationwide [
WA, the continuing high rates of carriage despite
vaccination indicate an ongoing contribution of
environmental factors to acquisition of pneumococcus.
The main factors associated with detection of
pneumococcal carriage in our analysis were young age, presence of
nasal discharge and household crowding. The age
distribution of pneumococcal carriage—increasing each month
of the first year and declining slowly thereafter—has been
observed previously in Aboriginal children in WA [
correlates with the observed age distribution of OM which
is hyper-endemic in this population [
discharge was strongly associated with detection of
pneumococcal carriage (Table 3). The authors speculate that
pneumococcus plays a causative role in nasal discharge;
however, it is also possible that nasal discharge merely
improves detection of carriage. In either case, reinforcement
of hygiene practices would be important for limiting
transmission of pneumococcal strains.
The relationship between household crowding and
pneumococcal carriage has been reaffirmed in this study.
Previously crowding was linked with high carriage in a
study conducted in communities surrounding Kalgoorlie
in WA [
] and in other indigenous communities
including Alaska Native people [
]. While not shown to
be an independent risk factor in this analysis, ETS
exposure was reported more frequently among those with
pneumococcal carriage (univariable OR 1.24 [95% CI
1.06–1.46]) and this has previously been associated with
both pneumococcal carriage [
] and OM in Aboriginal
8, 19, 20
]. These associations reinforce the
need to promote healthy living conditions for Aboriginal
people and the importance of smoking prevention
Recent antibiotic use was strongly negatively associated
with detection of pneumococcal carriage (Table 3). There
was no appreciable change in rates of antibiotic resistance
among carriage isolates over the study, apart from a
decrease in resistance to cotrimoxazole in the post-PCV13
period (Table 2). Crude χ2 tests of carriage of
nonsusceptible strains of pneumococcus or multi-resistant
strains versus recent antibiotic use identified no significant
differences between the groups (data not shown). Taken
together, these findings suggest that recent antibiotic use
may be protective against pneumococcal carriage.
After adjusting for age, date, gender, remoteness, and
other factors, there was no evidence that the prevalence
of carriage of all serotypeable pneumococci across all
age groups decreased after introduction of PCV13
(Table 3). Among children <5 years old, those most
likely to have been vaccinated with PCV13, the
prevalence of carriage across all serotypes did not change
significantly (Table 1) but there was evidence of a
significant decrease in carriage of both PCV7 and
PCV13 serotypes (Table 1, Fig. 2). A similar reduction
in vaccine serotypes was previously reported in Alaska
Native children [
]. It appears that non-vaccine strains
are replacing vaccine-type strains after PCV13
introduction, rather than PCV13 reducing carriage overall.
This study was unable to investigate possible herd
immunity in more detail, particularly in infants <6 months
old, due to low enrolment numbers in this age group.
Carriage of PCV13 serotypes was also numerically
reduced in the older age groups studied (Table 1), albeit
to a lesser extent than in children <5 years old.
PostPCV13 vaccination coverage was estimated at ≥82%
among 5–14 year olds (Table 1), and the Australian
National Centre for Immunisation Research and
Surveillance estimates PCV vaccination coverage in Aboriginal
children in WA at >88% [
]. The numerical reduction
in PCV serotypes in older study participants is
consistent with an indirect effect of PCV13.
There were a number of strengths to this study, chiefly
the large sample size, spread over a broad geographic
region over several years. However there were also several
limitations. The opportunistic nature of sampling meant
the study did not achieve similar coverage of inhabitants
in all communities, and certain seasons were favoured
for visiting certain areas due to easier access by road/air
compared to rainy seasons. This meant some regions/
seasons may have been comparatively under-represented
in some analyses. Immunization status for all children in
this study could not be ascertained, due to an inability
to identify ACIR records for some participants. This was
primarily due to the method used to access immunization
data: participants were identified by name and date of
birth, as documented on records during interviews. It is
common among Aboriginal communities for individuals
to be identified by several different names and spellings
can vary for the same person; thus the data could not
always be matched to a record on the ACIR database.
Because most children <5 years old post-PCV13
appeared to have received at least one dose of PCV13, the
reduction in PCV13-non-PCV7 serotypes may have been
directly influenced by PCV13 vaccination. However,
greater decreases in PCV13 serotype carriage were noted
in Alaskan [
] and Massachusetts children [
following PCV13 introduction. Due to the uncertainty in
vaccination status for a large proportion of participants, and
the small number of children confirmed as PCV13
vaccinated (n = 37, Table 2), vaccination status was not
included as a variable in the risk factor analysis. Another
limitation of the study was the lack of detailed
information to allow accurate assessment of indirect effects
within households. It would be highly informative to
analyse carriage and possible transmission between
household members, and to assess the impact of
vaccination status of children on other household members.
However, in the communities studied, movement of
family members between houses and communities is
often dynamic rather than static, so such an analysis is
likely to be imprecise.
Despite observing reduced carriage of 6C and 19A in
children, these serotypes remained among the most
common serotypes carried following PCV13 introduction. The
reduction in carriage of serotypes 6A, 23F and 19A is
plausibly attributable to PCV13 as they are vaccine serotypes.
The reduction in 6C in children <5 years old may be
attributable to cross-protection from 6A which is covered by
]. The increase in non-vaccine types, most
notably 11A, 7B and 15B warrants further monitoring.
Increases in 11A and serogroup 15 have been reported
from other regions and countries. IPD caused by serogroup
15 increased in Norway after PCV13 introduction [
Serotype 11A was identified as an emerging serotype in the
Northern Territory Aboriginal population following PCV7
], and carriage of 11A also increased in
Sweden and Japan following PCV13 introduction [
Moreover, high rates of antimicrobial resistance among
serotypes 23F, 7B and 9 V are particularly concerning and
warrant close surveillance (Table 2).
While PCV13 appears to have influenced the
distribution of carriage serotypes among Aboriginal children in
WA, the overall rate of pneumococcal carriage remains
high across all age groups, with replacement of vaccine
serotypes with emerging non-vaccine serotypes. The
relevance of emerging carriage serotypes to IPD and
more common pneumococcal manifestations of OM and
pneumonia needs to be carefully assessed to properly
understand the impact of conjugate vaccination.
23vPPV: 23-valent pneumococcal polysaccharide vaccine; ACIR: Australian
Childhood Immunisation Register; CI: Confidence interval; ETS: Environmental
tobacco smoke; IPD: Invasive pneumococcal disease; OM: Otitis media;
OR: Odds ratio; PCV13: 13-valent pneumococcal conjugate vaccine; PCV7: 7-valent
pneumococcal conjugate vaccine; WA: Western Australia
We thank the communities and the staff of Aboriginal Medical Services and
Community Health Services who facilitated our study visits. We are grateful
to all the study participants.
Funding for this study was provided by WA Department of Health through
the Collaboration for Applied Research and Evaluation (CARE) and NHMRC
Project Grant #545232. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
Availability of data and materials
The datasets from the current study can be shared by the corresponding
author on reasonable request.
Conception, generation and design of the research plan: DL, AJL, AH. Data
collection: AH, DC, JB, KS, NAS. Data analysis: DC, TS. Drafting of manuscript:
DC, TS, DL. All authors performed critical review of the manuscript. All authors
read and approved the final manuscript.
Ethics approval and consent to participate
Ethical approval was granted by the Princess Margaret Hospital for Children
Ethics Committee, the Western Australian Country Health Service Board Research
Ethics Committee and the Western Australian Aboriginal Health Ethics Committee.
Local approval to approach communities in the Kimberley region was granted by
the Kimberley Aboriginal Health Planning Forum. Consent was sought from
parents or guardians of children included in the study.
Consent for publication
DL has previously been a member of the GSK Australia
PneumococcalHaemophilus influenzae-Protein D conjugate vaccine (“PhiD-CV”) Advisory
Panel, has received support from Pfizer Australia and GSK Australia to
attend conferences, has received an honorarium from Merck Vaccines to
give a seminar at their offices in Pennsylvania and support to attend a
conference, and is an investigator on an investigator-initiated research
grant funded by Pfizer Australia. AJL has received research funding and
support to attend conferences from GlaxoSmithKline and Pfizer Australia. A
Hoskins has received support to attend conferences from Pfizer Australia. All
other authors have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
1. World Health Organization. Pneumococcal vaccines WHO position paper - 2012 . Wkly Epidemiol Rec. 2012 ; 87 : 129 - 44 .
2. Lehmann D , Willis J , Moore HC , Giele C , Murphy D , Keil AD , et al. The changing epidemiology of invasive pneumococcal disease in Aboriginal and non-Aboriginal Western Australians from 1997 through 2007 and emergence of non-vaccine serotypes . Clin Infect Dis . 2010 ; 50 : 1477 - 86 .
3. Lehmann D , Weeks S , Jacoby P , Elsbury D , Finucane J , Stokes A , et al. Absent otoacoustic emissions predict otitis media in young Aboriginal children: a birth cohort study in Aboriginal and non-Aboriginal children in an arid zone of Western Australia . BMC Pediatr . 2008 ; 8 : 32 .
4. de Kluyver R , Enhanced Invasive Pneumococcal Disease Surveillance Working Group. Invasive pneumococcal disease surveillance Australia , 1 January to 31 March 2015. Commun Dis Intell Q Rep . 2015 ; 39 : E308 - 11 .
5. Giele CM , Keil AD , Lehmann D , Van Buynder PG. Invasive pneumococcal disease in Western Australia: emergence of serotype 19A . Med J Aust. 2009 ; 190 : 166 .
6. The Australian Immunisation Handbook . Canberra: Australian Government Department of Health; 2013 .
7. Jayasinghe S , Menzies R , Chiu C , Toms C , Blyth CC , Krause V , et al. Long-term impact of a "3 + 0" schedule for 7- and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in Australia, 2002 - 2014 . Clin Infect Dis . 2017 ; 64 : 175 - 83 .
8. Mackenzie GA , Leach AJ , Carapetis JR , Fisher J , Morris PS . Epidemiology of nasopharyngeal carriage of respiratory bacterial pathogens in children and adults: cross-sectional surveys in a population with high rates of pneumococcal disease . BMC Infect Dis . 2010 ; 10 : 304 .
9. Collins DA , Hoskins A , Bowman J , Jones J , Stemberger NA , Richmond PC , et al. High nasopharyngeal carriage of non-vaccine serotypes in Western Australian Aboriginal people following 10 years of pneumococcal conjugate vaccination . PLoS One . 2013 ; 8 : e82280 .
10. Dunne EM , Carville K , Riley TV , Bowman J , Leach AJ , Cripps AW , et al. Aboriginal and non-Aboriginal children in Western Australia carry different serotypes of pneumococci with different antimicrobial susceptibility profiles . Pneumonia . 2016 ; 8 : 1 - 9 .
11. Jacoby P , Carville KS , Hall G , Riley TV , Bowman J , Leach AJ , et al. Crowding and other strong predictors of upper respiratory tract carriage of otitis media-related bacteria in Australian Aboriginal and non-Aboriginal children . Pediatr Infect Dis J . 2011 ; 30 : 480 - 5 .
12. Leach AJ , Stubbs E , Hare K , Beissbarth J , Morris PS . Comparison of nasal swabs with nose blowing for community-based pneumococcal surveillance of healthy children . J Clin Microbiol . 2008 ; 46 : 2081 - 2 .
13. Watson K , Carville K , Bowman J , Jacoby P , Riley TV , Leach AJ , et al. Upper respiratory tract bacterial carriage in Aboriginal and non-Aboriginal children in a semi-arid area of Western Australia . Pediatr Infect Dis J . 2006 ; 25 : 782 - 90 .
14. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: seventh informational supplement M100- S17 . Wayne, Pennsylvania, USA: CLSI; 2007 .
15. Australian Bureau of Statistics. The Australian Statistical Geography Standard Remoteness Structure . Canberra: Australian Bureau of Statistics; 2011 .
16. Leach AJ , Wigger C , Andrews R , Chatfield M , Smith-Vaughan H , Morris PS . Otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules . BMC Pediatr . 2014 ; 14 : 200 .
17. Leach AJ , Wigger C , Beissbarth J , Woltring D , Andrews R , Chatfield MD , et al. General health, otitis media, nasopharyngeal carriage and middle ear microbiology in Northern Territory Aboriginal children vaccinated during consecutive periods of 10-valent or 13-valent pneumococcal conjugate vaccines . Int J Pediatr Otorhinolaryngol . 2016 ; 86 : 224 - 32 .
18. Reisman J , Rudolph K , Bruden D , Hurlburt D , Bruce MG , Hennessy T . Risk factors for pneumococcal colonization of the nasopharynx in Alaska Native adults and children . J Pediatric Infect Dis Soc . 2014 ; 3 : 104 - 11 .
19. Greenberg D , Givon-Lavi N , Broides A , Blancovich I , Peled N , Dagan R. The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers . Clin Infect Dis . 2006 ; 42 : 897 - 903 .
20. Jacoby PA , Coates HL , Arumugaswamy A , Elsbury D , Stokes A , Monck R , et al. The effect of passive smoking on the risk of otitis media in Aboriginal and non-Aboriginal children in the Kalgoorlie-Boulder region of Western Australia . Med J Aust. 2008 ; 188 : 599 - 603 .
21. Bruce MG , Singleton R , Bulkow L , Rudolph K , Zulz T , Gounder P , et al. Impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on invasive pneumococcal disease and carriage in Alaska . Vaccine. 2015 ; 33 : 4813 - 9 .
22. National Centre for Immunisation Research and Surveillance . Coverage estimates - Aboriginal and Torres Strait Islander children NSW: NCIRS; 2017 [updated 20 Apr 2017 ]. Available from: http://www.ncirs.edu.au/providerresources/coverage-information/ coverage-estimates-indigenous-children/.
23. Gounder PP , Bruce MG , Bruden DJ , Singleton RJ , Rudolph K , Hurlburt DA , et al. Effect of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae- Alaska , 2008 - 2012 . J Infect Dis . 2014 ; 209 : 1251 - 8 .
24. Loughlin AM , Hsu K , Silverio AL , Marchant CD , Pelton SI . Direct and indirect effects of PCV13 on nasopharyngeal carriage of PCV13 unique pneumococcal serotypes in Massachusetts' children . Pediatr Infect Dis J . 2014 ; 33 : 504 - 10 .
25. Cooper D , Yu X , Sidhu M , Nahm MH , Fernsten P , Jansen KU . The 13-valent pneumococcal conjugate vaccine (PCV13) elicits cross-functional opsonophagocytic killing responses in humans to Streptococcus pneumoniae serotypes 6C and 7A . Vaccine . 2011 ; 29 : 7207 - 11 .
26. Steens A , Bergsaker MAR , Aaberge IS , Rønning K , Vestrheim DF . Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway . Vaccine. 2013 ; 31 : 6232 - 8 .
27. Leach AJ , Morris PS , McCallum GB , Wilson CA , Stubbs L , Beissbarth J , et al. Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001 . BMC Infect Dis . 2009 ; 9 : 121 .
28. Galanis I , Lindstrand A , Darenberg J , Browall S , Nannapaneni P , Sjöström K , et al. Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm. Sweden Eur Respir J . 2016 ; 47 : 1208 - 18 .
29. Kawaguchiya M , Urushibara N , Aung M , Morimoto S , Ito M , Kudo K , et al. Emerging non-PCV13 serotypes of noninvasive Streptococcus pneumoniae with macrolide resistance genes in northern Japan . New Microbes New Infect. 2016 ; 9 : 66 - 72 .