Skip to main content
PMC home page
Bulletin of the World Health Organization logoLink to Bulletin of the World Health Organization
. 2012 Dec 11;91(3):167–173. doi: 10.2471/BLT.12.109231

Increased paediatric hospitalizations for empyema in Australia after introduction of the 7-valent pneumococcal conjugate vaccine

Augmentation des hospitalisations pédiatriques dues à un empyème en Australie, après l'introduction du vaccin pneumococcique heptavalent conjugué

Aumento de las hospitalizaciones pediátricas por empiema en Australia tras la introducción de la vacuna conjugada antineumocócica heptavalente

زيادة عدد الأطفال الذين يتم إدخالهم إلى المستشفيات إثر إصابتهم بالدبيلة في أستراليا بعد إدخال اللقاح المتقارن المضاد لالتهاب المكورات الرئوية السباعي

澳大利亚引进7 价肺炎球菌结合疫苗后更高的儿童脓胸症住院率

Участившиеся случаи госпитализации детей с эмпиемой в Австралии после введения семивалентной пневмококковой конъюгированной вакцины

Roxanne E Strachan a,✉, Thomas L Snelling b, Adam Jaffé c
PMCID: PMC3590619  PMID: 23476089

Abstract

Objective

To examine rates of paediatric hospitalization for empyema and pneumonia in Australia before and after the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7).

Methods

Rates of paediatric hospitalization for empyema and pneumonia (bacterial, viral and all types) were calculated following the codes of the International Classification of Diseases, tenth revision (ICD-10) as a principal diagnosis. The expected number of hospitalizations after the PCV7 was introduced was estimated on the basis of the observed number of hospitalizations before the introduction of the PCV7. Incidence rate differences (IRDs) and incidence rate ratios (IRRs) were calculated. Hospitalization incidence in each study period was expressed as the number of hospitalizations per million (106) person–years. The population of children aged 0–19 years in Australia from 1998 to 2004 and from 2005 to 2010, as reported by the Australian Bureau of Statistics, was used to calculate the number of person–years in each period.

Findings

In the 5 years following the introduction of the PCV7, hospitalizations for pneumonia were fewer than expected (15 304 fewer; 95% confidence interval, CI: 14 646–15 960; IRD: −552 per 106 person–years; 95% CI: −576 to −529 per 106 person–years; IRR: 0.78; 95% CI: 0.77–0.78). Hospitalizations for empyema, on the other hand, were more than expected (83 more; 95% CI: 37–128; IRD: 3 per 106 person–years; 95% CI: 1–5 per 106 person–years; IRR: 1.35; 95% CI: 1.14–1.59). Reductions in hospitalizations were observed for all ICD-10 pneumonia codes across all age groups. The increase in empyema hospitalizations was only significant among children aged 1 to 4 years.

Conclusion

The introduction of the PCV7 in Australia was associated with a substantial decrease in hospitalizations for childhood pneumonia and a small increase in hospitalizations for empyema.

Introduction

Streptococcus pneumoniae is the leading cause of bacterial infection in children worldwide and the most common cause of bacterial pneumonia in Australia, where it accounts for approximately one third of all cases.1 In Australia, about 0.7% of all cases of pneumonia in children are complicated by empyema, which requires hospitalization for treatment and possible drainage.2 S. pneumoniae is also the most common pathogen causing empyema.3 The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Australia's national immunization programme in two phases: in 2001 for indigenous and immunocompromised children less than 2 years of age, and in January 2005 for all children in this age group. In July 2011 the PCV7 was replaced by a 13-valent conjugate vaccine. The PCV7 was administered as a three-dose series at ages 2, 4 and 6 months, without a booster.

Although pneumococcal conjugate vaccines have reduced invasive pneumococcal disease rates in children and adults throughout the world, 4–9 several studies have reported a concomitant increase in empyema cases, both in the vaccinated and the non-vaccinated population.10–17 Because up to 90% of these cases have been caused by bacterial serotypes not included in the PCV7,10–12 some fear that empyema may have emerged as a “replacement disease”, i.e. disease produced by non-vaccine-related serotypes that have become predominant. Although we have reported the rates of childhood empyema in Australia elsewhere,2 no previous studies have examined how the introduction of PCV7 has affected childhood empyema rates in this country. The objective of this study is to examine the incidence of paediatric hospitalizations for pneumonia and empyema in Australia before and after the introduction of the PCV7.

Methods

We reviewed the annual incidence in Australia of paediatric hospitalizations for empyema and pneumonia (viral and bacterial) before and after the introduction of PCV7 among children in the following age groups: < 1 year, 1–4 years, 5–9 years, 10–14 years and 15–19 years. The pre-vaccine period extended from July 1998 to June 2004; the post-vaccine period, from July 2005 to June 2010. We excluded all hospitalizations from July 2004 to June 2005 because the PCV7 was introduced midway through this period. In Australia, hospital discharges are coded for the principal diagnosis (primary cause) in accordance with the coding system of the International Classification of Diseases, tenth revision. The Australian Institute of Health and Welfare collated the national hospital discharge codes supplied by state and territory authorities per financial year, from July to June, and introduced them into the National Hospital Morbidity Database, which is publicly available. From this database we obtained data on the hospitalizations in the age groups already indicated. Although a “child” is generally defined as a person under the age of 18 years, data cubes were only available for these age groups. We included codes for bacterial pneumonia (J13–J15.9, J16.8, J18.0, J18.1, J18.8–J20.0) and viral pneumonia (J10.0, J11.0, J12.0–J12.2, J12.8, J12.9), as well as codes for empyema (J86–J86.9). We expressed hospitalization incidence as hospitalizations per 106 person–years and used census data for the population less than 20 years of age from the Australian Bureau of Statistics to calculate the number of person–years in each study period. There were 31 846 901 and 27 713 068 person–years in the pre- and post-vaccine periods, respectively.

We compared the incidence of hospitalization for all pneumonias, as well as for bacterial and viral pneumonia separately and for empyema, in the pre- and post-vaccine periods. We estimated the expected number of hospitalizations in the post-vaccine period by multiplying the hospitalization incidence rate in the pre-vaccine period by the number of person–years in the post-vaccine period. We also calculated incidence rate differences (IRD = incidence rate in pre-vaccine period minus incidence rate in post-vaccine period) and incidence rate ratios (IRR = incidence rate in post-vaccine period divided by incidence rate in pre-vaccine period) with their exact 95% confidence intervals (CIs), assuming a Poisson distribution.

Results

Overall, 78 552 and 53 052 pneumonia-coded hospitalizations took place in the periods before and after the introduction of the PCV7, respectively. The incidence of hospitalizations was 22% lower in the post-vaccine period than in the pre-vaccine period (IRR: 0.78; 95% CI: 0.77–0.78) (Fig. 1, Table 1). This reduction in hospitalization incidence was greatest among children whose age made them eligible for vaccination (i.e. < 1 year and 1 to 4 years in age) but was observed in all age groups. Most of the decrease in the incidence of hospitalizations was noted among children hospitalized for pneumonia with a bacteria-specific code (Table 1). In contrast, the incidence of hospitalizations coded as being for empyema was 35% higher (IRR: 1.35; 95% CI: 1.14–1.59) in the post-vaccine period than in the pre-vaccine period (Fig. 2, Table 1); the incidence of hospitalizations coded for viral pneumonia was 31% higher (IRR: 1.31; 95% CI: 1.27–1.35) (Table 1). However, the absolute increase in the incidence of hospitalizations for empyema and for viral pneumonia (3 and 70 hospitalizations more per 106 person–years, respectively) was much smaller than the absolute decrease in the incidence of hospitalization for bacterial pneumonia (623 hospitalizations fewer per 106 person–years). On subgroup analysis, the increase in empyema was only significant among children aged 1 to 4 years, which was the age group with the largest number of hospitalizations. There was little evidence of an increase in empyema among children born before the PCV7 became routinely available in Australia (i.e. those aged 5–9, 10–14 and 15–19 years).

Fig. 1.

Incidencea of hospital admissions for pneumonia, Australia, 1998–2004 and 2005–2010

a Number of hospitalizations per million (106) person­–years. There were 31 846 901 person–years in the period from July 1998 to June 2004 and 27 713 068 person–years in the period from July 2005 to June 2010.

Fig. 1

Open in a new tab

Table 1. Incidence rate differences (IRDs) and incidence rate ratios (IRRs) for paediatric hospitalizations for pneumonia and empyema before and after the introduction of the 7-valent pneumococcal conjugate vaccine, Australia.

Age group (years), by disease category July 1998 to June 2004
 July 2005 to June 2010
 IRDc (95% CI) IRRd (95% CI)
PY Hospitalizations Incidencea PY Hospitalizations (no.)
 Incidencea
Expectedb Observed
All pneumonias
0–19 31 846 901 78 552 2467 27 713 068 68 356 53 052 1914 −552 (−576 to −529) 0.78 (0.77 to 0.78)
< 1  1 499 975 10 894 7263 1 388 287 10 083 5938 4277 −2986 (−3160 to −2811) 0.59 (0.57 to 0.61)
1–4  6 186 032 42 258 6831 5 346 009 36 520 27 534 5150 −1681 (−1770 to −1592) 0.75 (0.74 to 0.78)
5–9  8 064 185 14 333 1777 6 726 493 11 955 10 667 1586 −192 (−233 to −150) 0.89 (0.87 to 0.91)
10–14 8 084 575 5785 716 7 011 457 5017 4510 643 −72 (−99 to −46) 0.90 (0.86 to 0.93)
15–19 8 012 134 5291 660 7 240 822 4782 4403 608 −52 (−78 to −27) 0.92 (0.88 to 0.96)
Bacterial pneumonia
0–19 31 846 901 71 338 2240 27 713 068 62 078 44 822 1617 −623 (−645 to −600) 0.72 (0.71 to 0.73)
< 1  1 499 975 9364 6243 1 388 287 8667 4761 3429 −2813 (−2973 to −2654) 0.55 (0.53 to 0.57)
1–4  6 186 032 37 493 6061 5 346 009 32 402 21 716 4062 −1999 (−2081 to −1917) 0.67 (0.66 to 0.68)
5–9  8 064 185 13 707 1700 6 726 493 11 433 9819 1460 −240 (−281 to −199) 0.86 (0.84 to 0.88)
10–14 8 084 575 5614 694 7 011 457 4869 4279 610 −84 (−110 to −58) 0.88 (0.84 to 0.91)
15–19 8 012 134 5160 644 7 240 822 4663 4247 587 −58 (−82 to −33) 0.91 (0.87 to 0.95)
Viral pneumonia
0–19 31 846 901 7223 227 27 713 068 6285 8230 297 70 (62 to 78) 1.31 (1.27 to 1.35)
< 1 1 499 975 1530 1020 1 388 287 1416 1177 848 −172 (−243 to −102) 0.83 (0.77 to 0.90)
1–4 6 186 032 4765 591 5 346 009 3159 5818 1088 318 (283 to 354) 1.41 (1.36 to 1.47)
5–9 8 064 185 626 78 6 726 493 522 848 126 48 (38 to 59) 1.62 (1.46 to 1.80)
10–14 8 084 575 171 21 7 011 457 150 231 33 12 (6 to 17) 1.56 (1.27 to 1.91)
15–19 8 012 134 131 16 7 240 822 118 156 22 5 (1 to 10) 1.32 (1.04 to 1.68)
Empyema
0–19 31 846 901 274 9 27 713 068 238 321 12 3 (1 to 5) 1.35 (1.14 to 1.59)
< 1 1 499 975 35 23 1 388 287 32 48 35 11 (−1 to 24) 1.48 (0.94 to 2.36)
1–4 6 186 032 96 16 5 346 009 83 146 27 12 (6 to 17) 1.76 (1.35 to 2.30)
5–9 8 064 185 39 5 6 726 493 33 31 5 0 (−2 to 2) 0.95 (0.57 to 1.57)
10–14 8 084 575 29 4 7 011 457 25 35 5 1 (−1 to 4) 1.39 (0.83 to 2.36)
15–19 8 012 134 71 9 7 240 822 64 61 8 0 (−3 to 3) 0.95 (0.66 to 1.36)
Open in a new tab

CI, confidence interval; PY, person–years.

a Hospitalizations per million (106) person–years.

b The number of hospitalizations expected in the post-vaccine period was derived by multiplying the hospitalization incidence rate in the pre-vaccine period by the number of person–years in the post-vaccine period.

c IRD is the incidence rate in pre-vaccine period minus incidence rate in post-vaccine period

d IRR is the incidence rate in post-vaccine period divided by incidence rate in pre-vaccine period

Fig. 2.

Incidencea of hospital admissions for empyema, Australia, 1998–2004 and 2005–2010

a Number of hospitalizations per million (106) person–years. There were 31 846 901 person–years in the period from July 1998 to June 2004 and 27 713 068 person–years in the period from July 2005 to June 2010.

Fig. 2

Open in a new tab

Discussion

Hospitalizations for childhood empyema in Australia appear to have increased after the introduction of the PCV7, despite a significant decrease in hospitalizations for pneumonia as a whole over the same period. The reduction in the incidence of hospitalizations for pneumonia was greatest among children whose age made them eligible for vaccination (i.e. < 1 year and 1–4 years in age), but more modest reductions were also observed among older children. Although the increase in the incidence of hospitalizations for empyema (which is present in fewer than 1% of pneumonia hospitalizations) was greatly outweighed by the reduction in the incidence of hospitalizations for pneumonia, empyema accounts for an important fraction of the cases of severe, complicated pneumonia. We assume that the IRDs we report here are primarily the result of vaccine-attributable changes in the epidemiology of childhood pneumonia in Australia, although they could also be reflecting other factors, including underlying secular trends. Our method is analogous to the method used in studies in England and Scotland on trends in childhood pneumonia and empyema.18,19

We based this analysis on publicly available hospitalization and population data. A limitation of the study is that we used hospital discharge data coded for the primary diagnosis. Bacterial pneumonias in children are difficult to distinguish from viral pneumonias because bacterial culture has a low positive yield. Furthermore, as many as 33% of the children with pneumonia are infected by mixed pathogens.20 Hence, the coding data may be inaccurate. To avoid this problem, we chose to compare the hospitalization rates for pneumonia as a whole rather than for bacteria-specific pneumonias. The reduction in hospitalizations for bacterial pneumonia was accompanied by a smaller absolute increase in pneumonias coded as viral (Table 1). This might reflect changes in coding practices or perhaps improvements in molecular diagnostics and a greater availability of viral antigens over time. Pneumonias coded as viral decreased among infants. This was also seen in a field trial of conjugate vaccine that demonstrated a reduction in viral pneumonia, presumably because viral pneumonia in young children is often complicated by co-infection with pneumococcus.21

Another limitation of our study is that we only included hospitalizations for which pneumonia and empyema were the primary diagnosis. Hence, our findings probably represent minimum estimates of disease incidence. Furthermore, we were unable to perform subgroup analysis by ethnic group and place of residence because these data are not publicly available.

For convenience, we examined the period preceding and the period following the introduction of the PCV7. Since the vaccine was introduced in January 2005, we excluded from the analysis all data for the period from July 2004 to June 2005 (Table 1). Nonetheless, the post-vaccine period included some children whose age would not have made them eligible for vaccination, and this could have resulted in an underestimation of the vaccine’s effect except in the youngest age group (< 1 year). In addition, targeted vaccination of indigenous children occurred during part of the pre-vaccine period. However, this probably affected our estimates only minimally since indigenous people account for only 3% of the Australian population.22

Although the PCV7 has substantially reduced the rates of invasive pneumococcal disease, reports from around the world suggest that the incidence of empyema in children has increased following the introduction of the PCV7.10,11 The reasons for this are not entirely clear, but virulent serotypes not covered by the PCV7 may have emerged as a result of the selective pressure applied by the vaccine. Most cases of empyema among Australian children are caused by serotypes 1, 3 and 19A,23 which are believed to be particularly virulent and more likely to invade the pleural cavity.24,25 The reported increase in serotypes 1, 3 and 19A among invasive isolates might explain the increase in empyema but not in pneumonia per se.10–12 On the other hand, an increase in the incidence of empyema was observed in some studies before the introduction of the PCV7.2,26–28 This suggests that the observed association between the introduction of the PCV7 and the rise in empyema incidence may be coincidental.

Irrespective of its cause, the observed increase in empyema adds to health system costs. In a clinical study in the United Kingdom of Great Britain and Northern Ireland, we calculated that the cost per admission for a child with empyema was between 7600 and 11 700 United States dollars (US$).29 A study in the United States yielded similar estimates.30 Thus, the 35% increase in empyema admissions observed in Australia following the introduction of the PCV7 has brought an additional expenditure of US$ 126 160–194 220 per year to the Australian health-care system. On the other hand, the reduction in pneumonia admissions has saved the health system US$ 3.8 million–6.1 million annually (based on United Kingdom cost-analysis data for pneumonia admissions).31 Although modest, the additional costs owing to the increase in cases of empyema among children would be reduced by the use of a vaccine with broader pneumococcal serotype coverage.3

In July 2011 (October 2011 in Australia’s Northern Territory), Australia’s 13-valent pneumococcal conjugate vaccine was introduced into the national immunization programme. This vaccine includes six serotypes that the PCV7 does not contain, including serotypes 1, 3 and 19A. Despite this, the large number of pneumococcal serotypes that have been identified makes it likely that other virulent pneumococcal strains will emerge. This underscores the need for on-going, enhanced molecular surveillance of invasive pneumococcal strains, including those that cause empyema in children. The results of such surveillance, which is already being practised in the United Kingdom, will directly affect future policy decisions regarding the adoption of newer vaccines as part of the national immunization schedule in Australia.

Competing interests:

AJ previously received an unrestricted grant from GlaxoSmithKline, Belgium.

References

  • 1.Burgner D, Richmond P. The burden of pneumonia in children: an Australian perspective. Paediatr Respir Rev. 2005;6:94–100. doi: 10.1016/j.prrv.2005.03.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Strachan R, Jaffé A, Australian Research Network in Empyema Assessment of the burden of paediatric empyema in Australia. J Paediatr Child Health. 2009;45:431–6. doi: 10.1111/j.1440-1754.2009.01533.x. [DOI] [PubMed] [Google Scholar]
  • 3.Strachan RE, Cornelius A, Gilbert GL, Gulliver T, Martin A, McDonald T, et al. Australian Research Network in Empyema Bacterial causes of empyema in children, Australia, 2007–2009. Emerg Infect Dis. 2011;17:1839–45. doi: 10.3201/eid1710.101825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Whitney CG, Farley MM, Hadler JL, Harrison LH, Bennett NM, Lynfield R, et al. Active Bacterial Core Surveillance of the Emerging Infections Program Network Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003;348:1737–46. doi: 10.1056/NEJMoa022823. [DOI] [PubMed] [Google Scholar]
  • 5.Centers for Disease Control and Prevention Invasive pneumococcal disease in children 5 years after conjugate vaccine introduction – eight states, 1998–2005. MMWR Morb Mortal Wkly Rep. 2008;57:144–8. [PubMed] [Google Scholar]
  • 6.Chapman KE, Wilson D, Gorton R. Serotype dynamics of invasive pneumococcal disease post-PCV7 and pre-PCV13 introduction in North East England. Epidemiol Infect. 2012;5:1–9. doi: 10.1017/S0950268812000763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Johnson DR, D’Onise K, Holland RA, Raupach JC, Koehler AP. Pneumococcal disease in South Australia: vaccine success but no time for complacency. Vaccine. 2012;30:2206–11. doi: 10.1016/j.vaccine.2011.12.119. [DOI] [PubMed] [Google Scholar]
  • 8.Kellner JD, Vanderkooi OG, MacDonald J, Church DL, Tyrrell GJ, Scheifele DW. Changing epidemiology of invasive pneumococcal disease in Canada, 1998–2007: update from the Calgary-area Streptococcus pneumoniae research (CASPER) study. Clin Infect Dis. 2009;49:205–12. doi: 10.1086/599827. [DOI] [PubMed] [Google Scholar]
  • 9.Lacapa R, Bliss SJ, Larzelere-Hinton F, Eagle KJ, McGinty DJ, Parkinson AJ, et al. Changing epidemiology of invasive pneumococcal disease among White Mountain Apache persons in the era of the pneumococcal conjugate vaccine. Clin Infect Dis. 2008;47:476–84. doi: 10.1086/590001. [DOI] [PubMed] [Google Scholar]
  • 10.Calbo E, Díaz A, Cañadell E, Fábrega J, Uriz S, Xercavins M, et al. Spanish Pneumococcal Infection Study Network Invasive pneumococcal disease among children in a health district of Barcelona: early impact of pneumococcal conjugate vaccine. Clin Microbiol Infect. 2006;12:867–72. doi: 10.1111/j.1469-0691.2006.1502_1.x. [DOI] [PubMed] [Google Scholar]
  • 11.Hendrickson DJ, Blumberg DA, Joad JP, Jhawar S, McDonald RJ. Five-fold increase in pediatric parapneumonic empyema since introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2008;27:1030–2. doi: 10.1097/INF.0b013e31817e5188. [DOI] [PubMed] [Google Scholar]
  • 12.Byington CL, Korgenski K, Daly J, Ampofo K, Pavia A, Mason EO. Impact of the pneumococcal conjugate vaccine on pneumococcal parapneumonic empyema. Pediatr Infect Dis J. 2006;25:250–4. doi: 10.1097/01.inf.0000202137.37642.ab. [DOI] [PubMed] [Google Scholar]
  • 13.Bekri H, Cohen R, Varon E, Madhi F, Gire R, Guillot F, et al. Streptococcus pneumoniae serotypes involved in children with pleural empyemas in France. Arch Pediatr. 2007;14:239–43. doi: 10.1016/j.arcped.2006.12.010. [DOI] [PubMed] [Google Scholar]
  • 14.Byington CL, Spencer LY, Johnson TA, Pavia AT, Allen D, Mason EO, et al. An epidemiological investigation of a sustained high rate of pediatric parapneumonic empyema: Risk factors and microbiological associations. Clin Infect Dis. 2002;34:434–40. doi: 10.1086/338460. [DOI] [PubMed] [Google Scholar]
  • 15.Calbo E, Garau J. Invasive pneumococcal disease in children: changing serotypes and clinical expression of disease. Clin Infect Dis. 2005;41:1821–2. doi: 10.1086/498316. [DOI] [PubMed] [Google Scholar]
  • 16.Obando I, Arroyo LA, Sanchez-Tatay D, Moreno D, Hausdorff WP, Brueggemann AB. Molecular typing of pneumococci causing parapneumonic empyema in Spanish children using multilocus sequence typing directly on pleural fluid samples. Pediatr Infect Dis J. 2006;25:962–3. doi: 10.1097/01.inf.0000235684.89728.38. [DOI] [PubMed] [Google Scholar]
  • 17.Obando I, Arroyo LA, Sanchez-Tatay D, Tarrago D, Moreno D, Hausdorff WP, et al. Molecular epidemiology of paediatric invasive pneumococcal disease in southern Spain after the introduction of heptavalent pneumococcal conjugate vaccine. Clin Microbiol Infect. 2007;13:347–8. doi: 10.1111/j.1469-0691.2006.01646.x. [DOI] [PubMed] [Google Scholar]
  • 18.Roxburgh CS, Youngson GG, Townend JA, Turner SW. Trends in pneumonia and empyema in Scottish children in the past 25 years. Arch Dis Child. 2008;93:316–8. doi: 10.1136/adc.2007.126540. [DOI] [PubMed] [Google Scholar]
  • 19.Koshy E, Murray J, Bottle A, Sharland M, Saxena S. Impact of the seven-valent pneumococcal conjugate vaccination (PCV7) programme on childhood hospital admissions for bacterial pneumonia and empyema in England: national time-trends study, 1997–2008. Thorax. 2010;65:770–4. doi: 10.1136/thx.2010.137802. [DOI] [PubMed] [Google Scholar]
  • 20.Harris M, Clark J, Coote N, Fletcher P, Harnden A, McKean M, et al. British Thoracic Society Standards of Care Committee British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011. Thorax. 2011;66(Suppl 2):ii1–23. doi: 10.1136/thoraxjnl-2011-200598. [DOI] [PubMed] [Google Scholar]
  • 21.Madhi SA, Klugman KP, Vaccine Trialist Group A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med. 2004;10:811–3. doi: 10.1038/nm1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Australian Bureau of Statistics [Internet]. Aboriginal and Torres Strait Islander population estimates, 2011 – preliminary. Camberra: ABS; 2012. Available from: http://www.abs.gov.au/ausstats/abs@.nsf/Latestproducts/3101.0Feature%20Article1Mar%202012?opendocument&tabname=Summary&prodno=3101.0&issue=Mar%202012&num=&view= [accessed 10 December 2012].
  • 23.Strachan RE, Cornelius A, Gilbert GL, Gulliver T, Martin A, McDonald T, et al. Pleural fluid nucleic acid testing enhances pneumococcal surveillance in children. Respirology. 2012;17:114–9. doi: 10.1111/j.1440-1843.2011.02035.x. [DOI] [PubMed] [Google Scholar]
  • 24.Hausdorff WP, Feikin DR, Klugman KP. Epidemiological differences among pneumococcal serotypes. Lancet Infect Dis. 2005;5:83–93. doi: 10.1016/S1473-3099(05)01280-6. [DOI] [PubMed] [Google Scholar]
  • 25.Luján M, Gallego M, Belmonte Y, Fontanals D, Vallès J, Lisboa T, et al. Influence of pneumococcal serotype group on outcome in adults with bacteraemic pneumonia. Eur Respir J. 2010;36:1073–9. doi: 10.1183/09031936.00176309. [DOI] [PubMed] [Google Scholar]
  • 26.Eastham KM, Freeman R, Kearns AM, Eltringham G, Clark J, Leeming J, et al. Clinical features, aetiology and outcome of empyema in children in the north east of England. Thorax. 2004;59:522–5. doi: 10.1136/thx.2003.016105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Playfor SD, Smyth AR, Stewart RJ. Increase in incidence of childhood empyema. Thorax. 1997;52:932. [PubMed] [Google Scholar]
  • 28.Singleton RJ, Hennessy TW, Bulkow LR, Hammitt LL, Zulz T, Hurlburt DA, et al. Invasive pneumococcal disease caused by nonvaccine serotypes among Alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA. 2007;297:1784–92. doi: 10.1001/jama.297.16.1784. [DOI] [PubMed] [Google Scholar]
  • 29.Sonnappa S, Cohen G, Owens CM, van Doorn C, Cairns J, Stanojevic S, et al. Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema. Am J Respir Crit Care Med. 2006;174:221–7. doi: 10.1164/rccm.200601-027OC. [DOI] [PubMed] [Google Scholar]
  • 30.St Peter SD, Tsao K, Harrison C, Jackson MA, Spilde TL, Keckler SJ, et al. Thoracoscopic decortication vs tube thoracostomy with fibrinolysis for empyema in children: a prospective, randomized trial. J Pediatr Surg. 2009;44:106–11. doi: 10.1016/j.jpedsurg.2008.10.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Lorgelly PK, Atkinson M, Lakhanpaul M, Smyth AR, Vyas H, Weston V, et al. Oral versus i.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis. Eur Respir J. 2010;35:858–64. doi: 10.1183/09031936.00087209. [DOI] [PubMed] [Google Scholar]

Articles from Bulletin of the World Health Organization are provided here courtesy of World Health Organization

RESOURCES