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Pneumococcal vaccination and otitis media in Australian Aboriginal infants: comparison of two birth cohorts before and after introduction of vaccination
© Mackenzie et al; licensee BioMed Central Ltd. 2009
Received: 26 October 2008
Accepted: 19 February 2009
Published: 19 February 2009
Aboriginal children in remote Australia have high rates of complicated middle ear disease associated with Streptococcus pneumoniae and other pathogens. We assessed the effectiveness of pneumococcal vaccination for prevention of otitis media in this setting.
We compared two birth cohorts, one enrolled before (1996–2001), and the second enrolled after introduction of 7-valent pneumococcal conjugate and booster 23-valent polysaccharide vaccine (2001–2004). Source populations were the same for both cohorts. Detailed examinations including tympanometry, video-recorded pneumatic otoscopy and collection of discharge from tympanic membrane perforations, were performed as soon as possible after birth and then at regular intervals until 24 months of life. Analyses (survival, point prevalence and incidence) were adjusted for confounding factors and repeated measures with sensitivity analyses of differential follow-up.
Ninety-seven vaccinees and 51 comparison participants were enrolled. By age 6 months, 96% (81/84) of vaccinees and 100% (41/41) of comparison subjects experienced otitis media with effusion (OME), and by 12 months 89% and 88% experienced acute otitis media (AOM), 34% and 35% experienced tympanic membrane perforation (TMP) and 14% and 23% experienced chronic suppurative otitis media (CSOM). Age at the first episode of OME, AOM, TMP and CSOM was not significantly different between the two groups. Adjusted incidence of AOM (incidence rate ratio: 0.88 [95% confidence interval (CI): 0.69–1.13]) and TMP (incidence rate ratio: 0.63 [0.36–1.11]) was not significantly reduced in vaccinees. Vaccinees experienced less recurrent TMP, 9% (8/95) versus 22% (11/51), (odds ratio: 0.33 [0.11–1.00]).
Results of this study should be interpreted with caution due to potential bias and confounding. It appears that introduction of pneumococcal vaccination among Aboriginal infants was not associated with significant changes in prevalence or age of onset of different OM outcomes or the incidence of AOM or TMP. Vaccinees appeared to experience reduced recurrence of TMP. Ongoing high rates of complicated OM necessitate additional strategies to prevent ear disease in this population.
Young Aboriginal children in remote Australia have a 24% prevalence of tympanic membrane perforation (TMP) and 15% to 24% prevalence of chronic suppurative otitis media (CSOM). The World Health Organization states that CSOM prevalence greater than 4% indicates a massive public health problem.
Among Aboriginal infants, Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis have been isolated from 57%, 34% and 4% of TMPs respectively, with H. influenzae and S. pneumoniae co-infection in 28% of cases. Pneumococcal serotypes associated with TMP are 19A, 19F, 23F, 14 and 1. The 7-valent pneumococcal conjugate vaccine (7PCV) includes three of these: 19F, 23F and 14 as well as serotypes 4, 6B, 9V and 18C. Trials of 7PCV suggest efficacy of 6% against acute otitis media (AOM) in American and Finnish children[6, 7] with greater efficacy against more severe outcomes (9% to 10% against recurrent AOM and 23% to 39% against tympanostomy procedures). Two studies have reported 100% efficacy against TMP due to vaccine serotypes, excluding 19F[8, 10]. Efficacy against any TMP or CSOM is unknown. We thought that 7PCV might be even more effective in populations with a high burden of severe otitis (Australian Aboriginal children and others with substantial prevalence of CSOM [11–14]). Pneumococcal vaccination for Aboriginal children in Australia began in late 2001. We compared: 1) time to develop otitis media with effusion (OME) and other OM outcomes, 2) OM prevalence outcomes and 3) OM incidence outcomes in two birth cohorts of Aboriginal infants, before and after introduction of pneumococcal vaccination.
Two cohorts were enrolled from three Aboriginal communities on the Tiwi islands north of Darwin (population 2,029). We compared a cohort that received pneumococcal vaccination (2001–2004) with a comparison cohort from the same communities prior to vaccine availability (1996–2001).
The comparison, or before vaccine group, was enrolled in a randomised controlled trial of long-term amoxicillin versus placebo between 1996 and 2001 (OM-RCT). As subjects enrolled in the OM-RCT began randomised therapy after detection of the first OME episode, the comparison group for the time to first OME outcome included all subjects enrolled in the OM-RCT. For all other outcomes, the comparison group comprised only those participants assigned to placebo. The vaccinated group was enrolled between 2001 and 2004, after catch-up vaccination for those less than 2 years of age, and introduction of routine pneumococcal vaccination in July 2001.
Comparison group exclusion criteria were: age >12 months, gestation <34 weeks, penicillin sensitivity, long-term antibiotic therapy, craniofacial abnormality, CSOM and immunodeficiency. Exclusion criteria for the vaccinated group were: age >4 months, gestation <34 weeks and congenital abnormality.
Consent and Ethical Considerations
The mother or carer gave written informed consent for each study. The Institutional Ethics Committee of Territory Health Services and Menzies School of Health Research, and the Tiwi Health Board approved the studies.
Comparison participants were enrolled as soon as possible after birth and examined every two weeks until OME was detected. They were then randomised to amoxicillin or placebo until middle ear status was normal. Children received randomised therapy and monthly examinations for an average of 5.2 months. Vaccinees were also enrolled as soon as possible after birth and examined every two weeks until OME was detected, and then monthly until 12 months of age. Both groups were examined at 12, 18 and 24 months of age or until study completion.
All participants received standard care, including vaccinations, from community clinics. Vaccinees were scheduled to receive 7PCV at 2, 4 and 6 months of age and 23-valent polysaccharide vaccine (23PPV) at 18 months. The research team provided additional clinical care if new problems were identified during assessment. Medications provided by the study and community clinic were supervised for the comparison group but not for vaccinees. Standard antibiotic therapy for AOM among the vaccinated cohort was amoxicillin 50 mg/kg/day for 7 days (research team) and 300 mg twice daily for 5 days (community clinic), and for the comparison group, amoxicillin 50 mg/kg/day for 5 days (research team) and 125 mg thrice daily for 5 days (community clinic).
Assessment involved direct and video-recorded pneumatic otoscopy, tympanometry (GSI 38 Auto-Tymp Grayson-Stadler) and review of clinic records. Two independent, unblinded assessors standardised video diagnoses in the two cohorts. Consensus between assessors' video diagnoses was required in both studies and if a diagnosis in the 1996–2001 cohort was changed. If assessors disagreed a third assessor resolved the decision. Data were recorded using standard forms.
• OME: Type B tympanogram with neutral or mild bulging of the TM.
• AOM: Moderate or marked bulging of the TM. New episodes were defined when the preceding examination was OME or normal.
• TMP: Discharge through a perforation for <6 weeks or pus in the auditory canal. New episodes were defined when the preceding examination was AOM, OME or normal.
• CSOM: TMP with discharge for 6 weeks or greater.
Microbiology of Tympanic Membrane Perforations
Microbiological techniques were the same for both groups. Aluminium-shafted, cotton-tipped swabs (Disposable Products, Australia) of perforation discharge were collected through, or from as close as possible to, the site of perforation. Specimens were transported and stored frozen as recommended for pneumococcal carriage studies. Aliquots (10 μl) were cultured on selective media and incubated overnight at 37°C in 5% CO2. S. pneumoniae was confirmed with serotyping by the Quellung reaction, H. influenzae by dependence on X and V factors, and M. catarrhalis by colony morphology, Gram stain and oxidase production.
Vaccinee and placebo recipient data were compared, apart from the time to first OME outcome, for which comparison group data were included from all randomised subjects in the OM-RCT; i.e. before detection of OME and subsequent randomisation.
For time to first OME and AOM, data were included if the first examination was before 4 months of age. For time to first TMP and CSOM, data were included if the first examination was before 6 and 9 months of age respectively. Participant data were censored if the duration between consecutive examinations was greater than 2 months. Examinations after 24 months of age were excluded. To explore potential effects of unobserved clinical events because of differential follow-up, sensitivity analyses were performed including different ages at first examination (range less than 4 months to any age) and examination intervals (less than 2 to 6 months).
Analyses of pathogens associated with new perforation (specimen collected <28 days following new perforation) were performed per ear rather than per child. Recurrent (>1 episode in one ear) or bilateral perforation during follow-up were examined by log-linear modelling.
Time to first event outcomes used Kaplan-Meier curves and Cox proportional hazards models. Incidence outcomes used Poisson regression with estimates adjusted for repeated measures using generalised estimating equations. A priori analysis included adjustment for 'rate of non-respiratory illness' (incidence of presentations for diarrhoea, anaemia, failure to thrive, skin sores, scabies and fungal infection) as a measure of general ill health between studies. Other potentially confounding variables (gender, age at first examination, rate of well and sick clinic visits, rate of prior antibiotic prescription, birth weight, delayed immunisation (>1 month after due date) were included in forward stepwise modeling if p-values were less than 0.10. Statistical significance was the 5% confidence level. Assuming a baseline median time to OME of 60 days, an alpha level of 0.05 with 100 vaccinated and 80 comparison participants, the comparison had power of 0.77 to detect a clinically important difference of 20 days. Assuming a baseline cumulative proportion experiencing TMP of 50%, alpha of 0.05 with 100 vaccinated and 50 comparison participants, the comparison had power of 0.82 to detect an expected reduction of 50% to a cumulative proportion of 25%.
Role of the Funding Source
The National Health & Medical Research Council of Australia funded the RCT. Wyeth Australia funded the vaccine study. Neither was involved in study design, collection, analysis, interpretation of data, writing or submission of the report.
Enrolment and Comparability of Groups
Vaccinated and comparison group characteristics
N = 97
N = 51
Mean Difference or Odds Ratio (95% CI)
Sex (% Male)
0.61 (0.29, 1.27)
Birth weight (g)
2956 (n = 87)
3159 (n = 49)
-203 (-409, 3)
Maternal age (years)
24.2 (n = 95)
23.0 (n = 49)
1.2 (-0.8, 3.1)
Clinical characteristics of vaccinated and comparison groups in the first 6 months of life
N = 94
N = 41
Mean Difference or Odds Ratio (95% CI)
Age at first examination (in days)
-18 (-31 – -5)
Well clinic visits
-5.48 (-7.21 – -3.75)
Sick clinic visits
-1.96 (-4.46 – 0.55)
Upper respiratory illnesses*
0.33 (-0.21 – 0.87)
Lower respiratory illnesses
-2.24 (-2.89 – -1.59)
0.09 (-1.06 – 1.24)
-0.24 (-0.76 – 0.28)
-0.97 (-2.30 – 0.37)
Failure to thrive
2.25 (0.24 – 109)
External nasal discharge
1.02 (0.45 – 2.31)
Admitted to hospital
0.84 (0.32 – 2.37)
0.22 (0.09 – 0.56)
Tests positive for anaemia‡
-12 (-40 – 15)
Comparing census data from 2001 and 1996, there were similar income levels, proportions of residents aged 0–4, and rates of unemployment (data not shown). Average household occupancy was lower in 2001 than 1996, 4.5 versus 5.1 occupants per house.[15, 19]
Prevalence of Otitis Media Outcomes in the First Year of Life
Cumulative proportions of participants over time with different otitis outcomes
Time to First Otitis Media Outcomes
Univariate and multivariate survival analyses of time to first event for different otitis outcomes, hazard ratios and 95% confidence intervals
Variable/s included in analyses
Vaccinated versus comparison group
1.17 (0.85 – 1.62)
0.80 (0.51 – 1.26)
0.84 (0.42 – 1.67)
0.57 (0.20 – 1.62)
Age at first examination (days)
0.98 (0.98 – 0.99)
1.00 (0.99 – 1.01)
0.79 (0.57 – 1.10)
1.06 (0.70 – 1.60)
0.99 (0.53 – 1.88)
0.36 (0.11 – 1.13)
Rate of non-respiratory illness*
1.09 (0.79 – 1.52)
1.08 (0.73 – 1.60)
1.07 (0.57 – 2.01)
0.98 (0.39 – 2.46)
Rate of prior antibiotic prescription*
0.71 (0.48 – 1.03)
0.91 (0.62 – 1.35)
0.95 (0.53 – 1.72)
1.63 (0.75 – 3.58)
Birth weight (kg)
0.99 (0.74 – 1.33)
1.04 (0.71 – 1.54)
0.90 (0.49 – 1.66)
0.94 (0.35 – 2.54)
Rate of well clinic visits*
1.10 (0.99 – 1.23)
1.32 (1.07 – 1.62)
1.09 (0.74 – 1.62)
1.10 (0.57 – 2.12)
0.64 (0.36 – 1.17)
0.69 (0.39 – 1.22)
0.66 (0.31 – 1.40)
1.19 (0.40 – 3.54)
Vaccinated versus comparison group
0.90 (0.64 – 1.25)
1.01 (0.61 – 1.67)
0.83 (0.41 – 1.66)
0.56 (0.19 – 1.62)
Age at first examination (days)
0.98 (0.97 – 0.99)
Rate of non-respiratory illness*
1.14 (0.83 – 1.56)
1.04 (0.71 – 1.52)
1.09 (0.58 – 2.07)
1.04 (0.42 – 2.60)
Rate of well clinic visits*
1.32 (1.05 – 1.65)
Unadjusted, Multivariate, and Sensitivity Analyses of the Incidence of Acute Otitis Media and Tympanic Membrane Perforation
Incidence of AOM and TMP in vaccinated and comparison groups, including sensitivity analyses
No. of participants
Examinations per year
No. of episodes
No. with 0 episodes (%)
No. with 1 episode (%)
No. with >1 episodes (%)
Absolute rate reduction†
Analysis of the incidence of new perforation included 94 vaccinees and 41 comparison participants. Unadjusted analysis showed vaccination associated with an ARR of new perforation of 0.27 episodes per person-year (0.82 in comparison and 0.55 in vaccinated participants; IRR: 0.68 [95% CI 0.40–1.14]). Increased incidence of new perforation was associated with increased antibiotic prescription and non-respiratory illness rate (data not shown). Multivariate modelling showed vaccination associated with an adjusted ARR of 0.28 episodes per person-year (0.75 in comparison and 0.47 in vaccinated participants; IRR: 0.65 [95% CI: 0.38–1.10]). Sensitivity analysis including any age at first examination and less than 4 month examination intervals (97 vaccinees, 51 comparison participants) resulted in a different adjusted ARR of 0.36 episodes per person-year (0.75 in comparison and 0.39 in vaccinated participants; IRR: 0.51 [95% CI: 0.31–0.84]). Recurrent perforation (>1 episode) occurred in 8% (8/97) of vaccinees and 22% (11/51) of comparison participants (odds ratio: 0.33 [95% CI: 0.11–1.00]) (Table 5).
Bilateral and Recurrent Tympanic Membrane Perforation
The number of participants experiencing unilateral or bilateral perforation and single or multiple episodes of perforation were analysed by log-linear modelling. Odds of both left and right TMP during follow-up in vaccinees were 0.41 [95% CI: 0.18–0.94) compared to comparison participants. Similarly, vaccinees had lower odds of multiple perforations 0.40 [95% CI: 0.18–0.87).
Pathogens isolated from new tympanic membrane perforations
Perforation pathogen category
N = 97 (194 ears)
N = 51 (102 ears)
73 (38% of ears)
72 (71% of ears)
New perforation discharge specimen collected
59/73 (81% new perforations)
44/72 (61% new perforations)
Positive discharge specimens*
32/59 (54% specimens)
25/44 (57% specimens)
19/32 (59% positive specimens)
16/25 (64% positive specimens)
All vaccine-related types
All non-vaccine types
S. pneumoniae & H. influenzae †
This is the first report of the impact of pneumococcal vaccination on any TMP and the natural history of OM in a high risk population. Introduction of vaccination was not associated with large effects on the outcomes of primary interest, delayed onset of OME and proportions of participants experiencing TMP. We also found that infant pneumococcal vaccination in remote Aboriginal communities was associated with, albeit with marginal significance:
a) Little effect on cumulative proportions of participants experiencing, or time to first episode of OME, AOM, TMP, or CSOM.
b) A reduced proportion developing CSOM at 9 months of age.
c) Trends towards reduced incidence of AOM and TMP in the first 2 years of life.
d) Reduced recurrence of TMP.
In addition, the consistent relationship of cumulative hazards for TMP between the groups, suggested that any effect of three doses of 7PCV did not wane before 12 months of age.
The lack of substantial benefit of pneumococcal vaccination for OM in this population is likely due to a combination of factors. Vaccination had little effect on the high prevalence of H. influenzae infection or co-infections of H. influenzae and S. pneumoniae. As with studies in Finland and the US, vaccination did not prevent otitis associated with serotypes 19F[7, 8] and 19A which were common in our study. Unlike Finnish and Czech Republic studies of AOM, our data indicate a trend towards increased risk of TMP associated with vaccine-related serotypes. The US also reports increased proportions of AOM associated with vaccine-related and non-vaccine serotypes in the post-7PCV era[21, 22]. Increased invasive 19A disease has been noted in post-7PCV surveillance among Alaska native and Massachusetts children. Although our findings do not support substantial replacement OM disease due to H. influenzae, they are consistent with US reports documenting potential H. influenzae replacement disease following 7PCV[22, 25, 26]. Limited serotype coverage of 7PCV (50% of comparison group perforations) also contributed to poor vaccine effectiveness. Finally, early age of onset (90% experienced OME and 50% experienced AOM by age 4 months; before the second dose of 7PCV) largely precludes an immunological response to vaccination affecting development of OM. Nonetheless, our finding that vaccinated children had fewer recurrent episodes of TMP suggests that a schedule stimulating an immune response before ear disease is established, e.g. maternal, neonatal or young infant dosing, may be more effective than a 2, 4, 6 month schedule. Although our study did not follow children for a sufficient duration to examine the effect of the 23PPV booster, immunogenicity has been demonstrated with the potential to widen the serotype coverage beyond the 7 serotypes included in the 7PCV. Earlier administration of the booster may be more effective than the 18 month dose although it remains unknown whether boosting with the 7PCV or 23PPV is more effective.
Our study was designed to detect expected large effects. Our results, are however, consistent with more modest effects which would still be important in this population. A further limitation is the use of historic comparisons, which raises the possibility of bias or confounding. Universal vaccination precluded the use of concurrent controls. Although there are limitations, the study setting and measures we have taken, minimise the limitations. Bias due to temporal changes is limited as historic data (1996–2001) are continuous with data collected after vaccine introduction (2001–2004). Ecological data suggested reduced household crowding over time but no change in levels of income, unemployment or the proportion of young children in the population. Bias towards a positive vaccine effect due to temporal improvements in child care practices, health services (e.g. more intensive antibiotic schedules) and environmental conditions is possible, however this was not evident from clinical characteristics before 6 months of age (Tables 1 &2), nor from the essentially non-significant effect that was observed. Potential confounding is reduced as otitis risk factors are universal in this population: breast feeding, absence of pacifiers, family history of otitis and extremely high rates of smoking. Study procedures were objective and held constant throughout the study period. We partially adjusted for potential bias of historic comparisons by adjusting for rates of non-respiratory illness as a surrogate measure of general ill health. Enrolment of 80% of the population in the vaccinated group and 54% in the comparison group, who were also involved in OM-RCT with more restrictive inclusion criteria and supervised therapy, introduced selection bias against a positive vaccine effect.
Due to potential confounding and bias, the results of this study should be interpreted with caution. Despite the association of infant pneumococcal vaccination with possible reductions in incidence of AOM and TMP, the cumulative proportion of Aboriginal children experiencing OME, AOM, TMP and CSOM was unchanged as was the time to development of different OM outcomes. Of note, the lack of vaccine effectiveness to substantially reduce proportions of participants experiencing different OM outcomes and delayed onset of OM does not imply evidence of no effect. This vaccination is unlikely to reduce the prevalence of ear disease in this population in the first years of life. Our findings have important implications for the generalisability of research conducted in affluent populations for high-risk disadvantaged populations. This assertion is supported by data from Navajo and White Mountain Apache infants, where 7PCV efficacy against clinically-diagnosed and severe OM was somewhat lower than in Californian and Finnish children. Results of post-7PCV licensure studies among affluent populations regarding OM[26, 28, 29], pneumonia and invasive disease have been very positive. However, 7PCV may have little effect against simple and suppurative ear disease and pneumonia in populations at very high risk of pneumococcal infection and those living in disadvantaged conditions which attribute such risk. Further study of infant cohorts is necessary to document longer term vaccine effectiveness which incorporates potentially increasing indirect effects over time. Thus, the results of efficacy studies and licensing and use of a 10-valent pneumococcal-Haemophilus protein D conjugate vaccine, similar to a product shown effective against OM in Europe, and a 13-valent PCV are much anticipated. Post-introduction studies of sufficient size, will be needed to better define the impact of these vaccines against complicated OM in the Aboriginal population. Apart from wider serotype coverage (particularly serotypes 19A, 6A and 16F), other potential avenues to improve the effectiveness of pneumococcal vaccines in this population include: maternal, neonatal or young infant vaccination and development of common pneumococcal antigen vaccines. Vaccines with efficacy against OM due to multiple pathogens are also needed. In the meantime, there should be ongoing focus on early detection and treatment of ear disease and hearing impairment, and the underlying, predominantly social and economic, determinants of ear infections in Aboriginal Australians.
Priscilla Tipakalippa, Chris Wigger and Grant Mackenzie were the primary field workers with assistance from Una Pilakui, Edna Gadil, J R Gadil, Gabrielle Mellon and Kate Wilson. Elizabeth Stubbs, Kim Hare, Brooke Hanson and Amanda Kennedy performed the laboratory work. Jemima Beissbarth was involved in laboratory work and assisted Robyn Liddle with data management. Al Yonovitz gave technical assistance with the video otoscopy equipment.
We acknowledge the children, families and Tiwi communities who were involved in the studies. We thank the community leaders, the Tiwi health board and the staff of local health clinics for their support. The study was funded by the National Health and Medical Research Council of Australia and Wyeth Australia. Menzies School of Health Research staff and facilities were essential to the success of the study. We thank the Cooperative Research Centre for Aboriginal and Tropical Health for valuable support.
Dr Mackenzie received a scholarship from the National Health & Medical Research Council of Australia.
This work is attributed to the Child Health Division, Menzies School of Health Research.
- Morris PS, Leach AJ, Silberberg P, Mellon G, Wilson C, Hamilton E, Beissbarth J: Otitis media in young Aboriginal children from remote communities in Northern and Central Australia: a cross sectional survey. BMC Pediatrics. 2005, 5: 27-10.1186/1471-2431-5-27.View ArticlePubMedPubMed CentralGoogle Scholar
- Rothstein J, Heazlewood R, Fraser M: Health of Aboriginal and Torres Strait Islander children in remote Far North Queensland: findings of the Paediatric Outreach Service. MJA. 2007, 186: 519-521.PubMedGoogle Scholar
- WHO/CIBA Foundation: Prevention of hearing impairment from chronic otitis media. Presented at a WHO/CIBA Foundation Workshop. 1996, 19-21. [http://www.noiseandhealth.org/article.asp?issn=1463-1741;year=1998;volume=1;issue=1;spage=6;epage=12;aulast=Smith]Google Scholar
- Leach AJ, Mackenzie GA, Hare K, Stubbs E, Beissbarth J, Kennedy M, Wigger C, Gadil JR, Morris P: Microbiology of acute otitis media with perforation (AOMwiP) in Aboriginal children living in remote communities – monitoring the impact of 7-valent pneumococcal conjugate vaccine (7vPCV). Streptococci: New Insights into an Old Enemy: 25–29 September 2005; Palm Cove. Edited by: Sriprakash KS. 2006, Elsevier Science: Philadelphia, 89-92.Google Scholar
- Leach AJ: Prospective studies of respiratory pathogens, particularly Streptococcus pneumoniae, in Aboriginal and non-Aboriginal infants: impact of antibiotic use and implications for otitis media. PhD thesis. 1996, University of SydneyGoogle Scholar
- Fireman B, Black SB, Shinefield HR, Lee J, Lewis E, Ray P: Impact of the pneumococcal conjugate vaccine on otitis media. Pediatr Infect Dis J. 2003, 22: 10-16. 10.1097/00006454-200301000-00006.View ArticlePubMedGoogle Scholar
- Eskola J, Kilpi T, Palmu A, Jokinen J, Haapakoski J, Herva E, Takala A, Kayhty H, Karma P, Kohberger R, Siber G, Makela PH: Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med. 2001, 344: 403-409. 10.1056/NEJM200102083440602.View ArticlePubMedGoogle Scholar
- Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen JR, Elvin L, Ensor KM, Hackell J, Siber G, Malinoski F, Madore D, Chang I, Kohberger R, Watson W, Austrian R, Edwards K: Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J. 2000, 19: 187-195. 10.1097/00006454-200003000-00003.View ArticlePubMedGoogle Scholar
- Palmu AA, Verho J, Jokinen J, Karma P, Kilpi TM: The seven-valent pneumococcal conjugate vaccine reduces tympanostomy tube placement in children. Pediatr Infect Dis J. 2004, 23: 732-738. 10.1097/01.inf.0000133049.30299.5d.View ArticlePubMedGoogle Scholar
- O'Brien KL, David AB, Chandran A, Moulton LH, Reid R, Weatherholtz R, Santosham M: Randomized, controlled trial efficacy of pneumococcal conjugate vaccine against otitis media among Navajo and White Mountain Apache infants. Pediatr Infect Dis J. 2008, 27: 71-73. 10.1097/INF.0b013e3181684d7c.View ArticlePubMedGoogle Scholar
- Minja BM, Moshi NH, Ingvarsson L, Bastos I, Grenner J: Chronic suppurative otitis media in Tanzanian school children and its effects on hearing. East Afr Med J. 2006, 83: 322-325.View ArticlePubMedGoogle Scholar
- Kamal N, Joarder AH, Chowdhury AA, Khan AW: Prevalence of chronic suppurative otitis media among the children living in two selected slums in Dhaka City. Bangladesh Med Res Counc Bull. 2004, 30: 95-104.PubMedGoogle Scholar
- Amusa YB, Ijadunola IK, Onayade OO: Epidemiology of otitis media in a local tropical African population. West Afr J Med. 2005, 24: 227-230.PubMedGoogle Scholar
- Matanda RN, Muyunga KC, Sabue MJ, Creten W, Heyning Van de P: Chronic suppurative otitis media and related complications at the University Clinic of Kinshasa. B-ENT. 2005, 1: 57-62.PubMedGoogle Scholar
- Australian Bureau of Statistics: ABS Website. 2001 Census doc. no. 71010 Bathurst-Melville (Statistical Local Area). 2002, ABS; Canberra, [http://www.censusdata.abs.gov.au/ABSNavigation/prenav/PopularAreas&collection=Census&period=2001&&navmapdisplayed=true&textversion=false]Google Scholar
- Leach AJ, Morris PS, Mathews JD: Compared to placebo, long-term antibiotics resolve otitis media with effusion and prevent acute otitis media with perforation in a high-risk population: a randomized double-blind placebo controlled trial. BMC Pediatrics. 2008, 8: 23-10.1186/1471-2431-8-23. [http://www.biomedcentral.com/1471-2431/8/23]View ArticlePubMedPubMed CentralGoogle Scholar
- O'Brien KL, Nohynek H, The WHO Pneumococcal Vaccine Trials Carriage Working Group: Report from a WHO Working Group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae. Pediatr Infect Dis J. 2003, 22: 133-140.View ArticlePubMedGoogle Scholar
- Leach AJ, Boswell JB, Asche V, Nienhuys TG, Mathews JD: Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian Aboriginal infants. Pediatr Infect Dis J. 1994, 13: 983-989.View ArticlePubMedGoogle Scholar
- Australian Bureau of Statistics: ABS Website. 1996 Census doc. no. 710100609 Bathurst-Melville (Statistical Local Area). 1997, ABS; Canberra, [http://www.abs.gov.au/AUSSTATS/abs@.nsf/96cdbygeogtype?openview&restricttocategory=Main%2020Areas&Expand=1&]Google Scholar
- Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, Kohl I, Lommel P, Poolman J, Prieels JP, Schuerman L: Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet. 2006, 367: 740-748. 10.1016/S0140-6736(06)68304-9.View ArticlePubMedGoogle Scholar
- McEllistrem MC, Adams JM, Patel K, Mendelsohn AB, Kaplan SL, Bradley JS, Schutze GE, Kim KS, Mason EO, Wald ER: Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis. 2005, 40: 1738-1744. 10.1086/429908.View ArticlePubMedGoogle Scholar
- Pichichero ME, Casey JR: Emergence of a multiresistant serotype 19A pneumococcal strain not included in the 7-valent conjugate vaccine as an otopathogen in children. JAMA. 2007, 298: 1772-1778. 10.1001/jama.298.15.1772.View ArticlePubMedGoogle Scholar
- Singleton RJ, Hennessy TW, Bulkow L, Hammitt LL, Zulz T, Hurlburt DA, Butler JC, Rudolph K, Parkinson A: Invasive pneumococcal disease caused by nonvaccine serotypes among Alaska Native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA. 2007, 297: 1784-1792. 10.1001/jama.297.16.1784.View ArticlePubMedGoogle Scholar
- Pelton SI, Huot H, Finkelstein JA, Bishop CJ, Hsu KK, Kellenburg J, Huang SS, Goldstein R, Hanage WP: Emergence of 19A as a virulent and multidrug resistant pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2007, 26: 468-472. 10.1097/INF.0b013e31803df9ca.View ArticlePubMedGoogle Scholar
- Block SL, Hedrick J, Harrison CJ, Tyler R, Smith A, Findlay R, Keegan E: Community-wide vaccination with heptavalent pneumococcal conjugate significantly alters the microbiology of acute otitis media. Pediatr Infect Dis J. 2004, 23: 829-833. 10.1097/01.inf.0000136868.91756.80.View ArticlePubMedGoogle Scholar
- Casey JR, Pichichero ME: Changes in frequency and pathogens causing acute otitis media in 1995–2003. Pediatr Infect Dis J. 2004, 23: 824-828. 10.1097/01.inf.0000136871.51792.19.View ArticlePubMedGoogle Scholar
- Leach AJ, Morris PS, Mackenzie G, McDonnell J, Balloch A, Carapetis J, Tang M: Immunogenicity for 16 serotypes of a unique schedule of pneumococal vaccines in a high-risk population. Vaccine. 2008, 26: 3885-3890. 10.1016/j.vaccine.2008.05.012.View ArticlePubMedGoogle Scholar
- Poehling KA, Szilagyi PG, Grijalva CG, Martin SW, Lafleur B, Mitchel E, Barth RD, Nuorti JP, Griffin MR: Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics. 2007, 119: 707-715. 10.1542/peds.2006-2138.View ArticlePubMedGoogle Scholar
- Fletcher MA, Fritzell B: Brief review of the clinical effectiveness of PREVENAR(R) against otitis media. Vaccine. 2006, 25: 2507-2512. 10.1016/j.vaccine.2006.09.027.View ArticlePubMedGoogle Scholar
- Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR: Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet. 2007, 369: 1179-1186. 10.1016/S0140-6736(07)60564-9.View ArticlePubMedGoogle Scholar
- Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, Reingold A, Cieslak PR, Pilishvili T, Jackson D, Facklam RR, Jorgensen JH, Schuchat A: Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003, 348: 1737-1746. 10.1056/NEJMoa022823.View ArticlePubMedGoogle Scholar
- O'Grady KA, Taylor-Thomson D, Chang A, Torzillo P, Morris P, Mackenzie G, Wheaton G, Bauert P, De Campo M, De Campo J, Ruben A: The burden of hospitalised, radiologically diagnosed pneumonia in Northern Terriotory Indigenous children in Australia. ISPPD-6 6th International Symposium on Pneumococci and Pneumococcal Diseases: 8–12 June 2008; Reykjavik. 2008, S01-03.Google Scholar
- Wyeth product pipeline: Wyeth website . [http://www.wyeth.com/research/projects]
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/9/14/prepub
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