International Journal of Clinical Practice

Int J Clin Pract. 68(1): 8-19

The burden of invasive pneumococcal disease in children with underlying risk factors in North America and Europe

M A Rose¹, D Christopoulou², T T H Myint³, I de Schutter⁴

1. Children's Hospital, Goethe UniversityFrankfurt, Germany

2. Pfizer LtdTadworth, Surrey

3. Pfizer PharmaceuticalsParis, France

4. Department of Pediatric Pulmonology, CF-Clinic and Pediatric Infectious Diseases, Universitair Ziekenhuis Brussel (UZ Brussel)Brussels, Belgium

Correspondence to:, Markus A. Rose,, Pneumologie / Allergologie / Infektiologie, Zentrum der Kinder- und Jugendmedizin, J.W. Goethe Universität,, Theodor Stern Kai 7, 60590 Frankfurt, Tel.: + 069 6301 5754, Fax: + 069 6301 6061, Email: Markus.Rose@kgu.de

Disclosures Markus A. Rose has received research funding and speaker's fees from Wyeth/Pfizer, Germany.

Dina Christopoulou is an employee of Pfizer Ltd, UK.

Tin Tin Htar Myint is an employee of Pfizer Pharmaceuticals, France.

Iris de Schutter has been an invited speaker for Pfizer and has participated in advisory boards for GlaxoSmithKline Biologicals and Pfizer in the past 3 years.

Linked Comment: Stein. Int J Clin Pract 2014; 68: 2–3.

© 2013 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.

DOI: 10.1111/ijcp.12234

Published in print: January 2014

Published online: 19 July 2013

Abstract

Summary

Background

Characterisation of risk groups who may benefit from pneumococcal vaccination is essential for the generation of recommendations and policy.

Methods

We reviewed the literature to provide information on the incidence and risk of invasive pneumococcal disease (IPD) in at-risk children in Europe and North America. The PubMed database was searched using predefined search terms and inclusion/exclusion criteria for papers reporting European or North American data on the incidence or risk of IPD in children with underlying medical conditions.

Results

Eighteen references were identified, 11 from North America and 7 from Europe, with heterogeneous study methods, periods and populations. The highest incidence was seen in US children positive for human immunodeficiency virus infection, peaking at 4167 per 100,000 patient-years in 2000. Studies investigating changes in incidence over time reported decreases in the incidence of IPD between the late 1990s and early 2000s. The highest risk of IPD was observed in children with haematological cancers or immunosuppression. Overall, data on IPD in at-risk children were limited, lacking incidence data for a wide range of predisposing conditions. There was, however, a clear decrease in the incidence of IPD in at-risk children after the introduction of 7-valent pneumococcal conjugate vaccine into immunisation programmes, as previously demonstrated in the general population.

Conclusion

Despite the heterogeneity of the studies identified, the available data show a substantial incidence of IPD in at-risk children, particularly those who are immunocompromised. Further research is needed to determine the true risk of IPD in at-risk children, particularly in the post-PCV period, and to understand the benefits of vaccination and optimal vaccination schedules.

Review criteria

The PubMed database was searched using predefined search terms, with predefined inclusion and exclusion criteria applied to the search results. Information from papers identified relevant to the research questions was tabulated in full, and summarised in the body of the manuscript.

Message for the clinic

Data on the incidence of IPD in children with underlying medical conditions are limited, and more research is needed to determine the true risk of disease. The available data show a substantial incidence of IPD in at-risk children, particularly those who are immunocompromised, with a corresponding increase in risk compared with healthy children.

Introduction

Invasive pneumococcal disease (IPD), which includes potentially fatal conditions such as meningitis, septicaemia and pneumonia, is responsible for an estimated 11% of all deaths worldwide in children aged < 5 years ¹. Before 2000, the only pneumococcal vaccine available was a 23-valent purified capsular polysaccharide vaccine (PPV-23), which is associated with poor or absent immunogenicity in children < 2 years of age and immunodeficient patients, and failure at any age to induce immunological memory following revaccination ².

A seven-valent pneumococcal conjugate vaccine (PCV-7) against key Streptococcus pneumoniae serotypes was licenced in the USA in February 2000 and subsequently in the European Union and Canada ³,⁴. Since then, many countries have introduced universal PCV immunisation programmes (between 2006 and 2008 in Europe, for example). In the USA and Canada, pneumococcal vaccination is recommended for universal childhood vaccination in children under 59 months of age, and in older children (60–71 months and >60 months of age, respectively) in individuals at high risk of IPD ⁵,⁶. In some European countries, such as the UK, France and Germany, PCV-7 was first recommended only for children at high risk of pneumococcal infection before being introduced into national immunisation programmes ³. These universal vaccination programmes with PCV-7 have led to major improvements in public health, with significant decreases in the incidence of vaccine-type IPD and, to a lesser extent, a decrease in overall IPD in most countries ⁴,⁷–¹⁰. As the introduction of PCV-7, however, the epidemiology of S. pneumoniae has evolved, with changes in serotype distribution ¹¹. Higher valent PCVs – PCV-10 and PCV-13 – have subsequently been introduced to adapt to these changes and have gradually superseded PCV-7 ².

In children, PCV-10 is licenced for those aged 6 weeks to 5 years, and PCV-13 is licenced for those aged 6 weeks to 17 years ¹²–¹⁴ – these vaccines are currently used in general childhood immunisation programmes – whereas PPV-23 is recommended for children ≥2 years of age in whom there is an increased risk of morbidity and mortality from pneumococcal disease ¹⁵. Some health authorities and scientific societies, however, also recommend the use of PCV-13 in a broader range of individuals at increased risk of IPD, particularly, those with underlying medical conditions such as innate or acquired immunodeficiency, deficient splenic function, cochlear implants or cerebrospinal fluid leak ¹⁶–¹⁹. Characterisation of those risk groups who may benefit from PCV-13 is essential for the generation of recommendations and for helping policy makers to produce policy for vaccination programmes based on the best available evidence ²⁰,²¹. We conducted, therefore, a literature review to provide up-to-date information on the incidence and risk of invasive IPD in Europe and North America in children with underlying conditions that place them at increased risk of IPD.

Methods

A search of the PubMed database was conducted using the following search string: ‘pneumococc* AND (pneumonia OR sinusitis OR meningitis OR bacteremia OR bacteraemia OR sepsis OR osteomyelitis OR septic arthritis OR endocarditis OR peritonitis OR pericarditis OR cellulitis OR soft tissue infection OR brain abscess OR mastoiditis OR empyema OR septicaemia OR “invasive pneumococcal disease” OR “invasive pneumococcal infection”)’. A built-in PubMed filter was used to limit the search to studies in children (0–18 years of age), and search results were limited to papers published in English between 1 January 2005 and 31 July 2012.

Papers were included in the review if they reported data from Europe or North America on the incidence or risk of IPD in ‘at-risk’ children, defined as those with underlying medical conditions placing them at increased risk of IPD (Table1).

See full tableTable 1. Risk categories for invasive pneumococcal disease included in the review*

Results

In total, 1640 references were identified by the literature search, of which 1435 were excluded on the basis of the title or abstract; the remaining 18 references met the inclusion and exclusion criteria (Figure1) ²²–³⁹. A further 10 papers were identified that reported incidence of IPD in indigenous populations and specific ethnic populations considered to be at increased risk of IPD ⁴⁰–⁴⁹. While these socioeconomic risk groups are outside the scope of this review, the details of these papers are presented in supplementary tables for the reader's interest (Tables S1 and S2).

Figure 1View larger versionFigure 1. Results of literature search and evaluation of identified studies according to Preferred Reporting Terms for Systematic Reviews and Meta-Analyses

Of the 18 included studies, six looked at several different time points within a specific period (1989–2006 ²⁴, 1995–2002 ²⁵,³¹, 1995–2004 ²⁶, 1996–2005 ²⁷ and 2001–2007 ³⁹). The other studies reported overall data in a single period of time: 1963–2003 ²³, 1964–2003 ³⁶, 1977–2005 ³², 1980–2005 ³⁷, 1990–2001 ²⁸, 1995–2000 ²⁹, 1995–2002 ³⁵, 1996–2002 ³⁸, 1997–2003 ³⁴, 1997–2004 ³⁰, 2001–2004 ³³ and 2008–2009 ²². Half of the studies were conducted in the USA ²⁴–²⁷,³⁰,³³,³⁵,³⁸,³⁹, three studies in the UK ²²,²³,²⁹, two each in Canada ²⁸,³¹ and Denmark ³²,³⁷, and one each in Germany ³⁴ and Sweden ³⁶. All 18 studies were conducted in children, although only two included children of any age from 0 to 18 years ²⁴,³¹. The remaining studies limited the age range of the children included (Tables2 and 3).

See full tableTable 2. Incidence of general invasive pneumococcal disease in children

See full tableTable 3. Incidence of specific forms of invasive pneumococcal disease in children

Sixteen of the 18 studies reported on IPD as a whole ²²–²⁹,³²–³⁹, although two of those 16 also looked at specific conditions (meningitis ²⁹ and bacteraemia ²⁴). The remaining two studies focused specifically on meningitis ³⁰,³¹. With regard to outcomes, six of the 18 studies included data only on the incidence of IPD ²⁴–²⁶,²⁹–³¹, eight included data only on risk ³²–³⁹, and the remaining four included both incidence and risk data ²²,²³,²⁷,²⁸.

Incidence of IPD

Data on the incidence of any IPD in at-risk children are shown in Table2. The overall incidence ranged from 1 to 4167 per 100,000 patient-years, with the exception of one study of human immunodeficiency virus [HIV] in US children. This study had no reported cases of IPD in children aged < 5 years after the introduction of highly active antiretroviral therapy in 1996, leading to a stated incidence of 0 in 2000 and 1997–1999 ²⁴. The highest incidence was seen in children aged > 5 years with HIV in the USA, peaking at 4167 per 100,000 patient-years in 2000 ²⁴. The incidence in children with sickle-cell disease in the USA was also high, with a peak of 3630 per 100,000 patient-years in 1995–1999 ²⁶, although two other studies reported lower incidences for a similar time period (170–301 per 100,000 patient-years) ²⁵,²⁷.

Across age groups, higher incidences of IPD were generally seen in younger vs. older children. In a study in children with sickle-cell disease, for example, the incidence in those aged < 2 years was 335–3630 per 100,000 patient-years, compared with 134–2044 for those aged < 5 years ²⁶. Similarly, a study in the UK in a predefined high-risk group (diabetes mellitus, chronic renal, hepatic or pulmonary disease, neoplastic disease, chronic immunosuppression) found an incidence of 38.6–75.3 per 100,000 patient-years in children aged < 1 year, compared with 1–11.6 per 100,000 patient-years in children aged 1–14 years ²⁹.

Three US database studies investigated the changing incidence of IPD over time in children with sickle-cell disease ²⁵–²⁷. All three studies showed large decreases in the incidence of IPD between the late 1990s and early 2000s, from 115–3630 per 100,000 patient-years in 1995–2000 to 26–335 in 2001–2005. Similar trends were observed in a retrospective US study in children with HIV in which the incidence decreased from 1862 in 1989–1995 to 860 in 2001–2006 ²⁴.

The incidence of IPD in different clinical presentations (meningitis and bacteraemia) in at-risk children is shown in Table3. Three studies described the incidence of meningitis (overall range: 0.2–400 per 100,000 patient-years) ²⁹–³¹. One survey described an increased incidence of meningitis in children with cochlear implants between 1995–98 and 1999–2000, after the introduction of cochlear implant positioners ³¹. The time between implantation and meningitis infection varied from 7 months to 7.7 years (median: 11 months). In at-risk children, the reported incidence of meningitis in the UK between 1995 and 2000 was higher in children < 11 months of age than in those aged 1–14 years ²⁹. Regarding other clinical manifestations, the incidence of bacteraemia in HIV-infected children (2008–2009) was 398 per 100,000 patient-years ²⁴.

Risk of IPD

Thirteen studies described the risk of IPD (Table4) in 18 different risk populations. The highest risk was observed in children with haematological cancers (adjusted risk ratio: 52.1 [95% confidence interval (CI): 13.7–198.2] ³²; standardised incidence ratio [age 5–9 years]: 50.6 [16.1–122.1] ³⁴) and immunosuppressed children (odds ratio: 41.0 [95% CI: 35.0–48.0]) ²², specifically those with HIV infection (odds ratio: 100.8 [95% CI: 44.7–227.2]) ²². Lower risk ratios (≤ 1.5) were reported for respiratory conditions ³²,³³, gastrointestinal disease ³² (including coeliac disease ²³), congenital immune deficiency ³², diabetes ³², cerebral palsy ³² and hydrocephalus ³².

See full tableTable 4. Risk of IPD in children

Discussion

This review has revealed the limited data available on the incidence of IPD in children with underlying medical conditions. Very few publications were from European countries, although it should be noted that non-English language publications were excluded from the search. Data on incidence in children were also absent for several conditions known to increase the risk of IPD in children and adults, such as cancer, diabetes mellitus, primary immunodeficiencies and other immune-mediated conditions ⁵⁰–⁵².

Despite the heterogeneity of study methods, periods and populations, the review clearly shows the increased risk of IPD in at-risk children, particularly those who are immunocompromised, compared with the incidence in the general paediatric population (estimated in the USA at 23.6 per 100,000 children aged < 5 years and at 2.4 per 100,000 in children aged 5–17 years) ⁵³. The incidence of IPD was highest in children with HIV, although one study in children with sickle-cell disease showed a similarly high incidence of IPD. When children of different age groups were compared, the youngest children (i.e. infants) generally had a higher incidence of IPD than older children, although there was still a substantial risk of disease in older children.

In studies in which different time points were described there was a clear decrease in the incidence of IPD after the introduction of PCV-7 vaccination into national immunisation programmes, as has also been observed in the general paediatric and adult populations ⁵⁴. Importantly, one of the case–controlled studies of IPD risk in children described a lower vaccination rate in children with IPD compared with non-IPD controls ³⁸. While PCVs have a limited number of serotypes, those included are associated with a marked clinical burden ⁵⁵–⁵⁹. Vaccination of high-risk children, regardless of age, does therefore provide an opportunity to protect them against IPD. It is noteworthy that PPV-23 vaccination of children older than 2 years and at risk of IPD is recommended in some countries. Unfortunately, pneumococcal vaccination coverage in high-risk children is relatively low compared with routine childhood vaccination with PCVs ⁶⁰–⁶². For example, an Italian study in children with HIV infection, cystic fibrosis, liver transplantation or diabetes mellitus found that pneumococcal vaccination rates were below 25% in each group ⁶⁰. Thus, there is a need for education of healthcare professionals, patients and families regarding the importance of vaccination in at-risk children. The increased risk of IPD with tobacco exposure also highlights the importance of broader educational programmes covering environmental factors that may affect disease risk, particularly in children with other risk factors.

Studies of risk described an increased risk of IPD in children with underlying conditions compared with controls. The highest risk of IPD was seen in immunocompromised children, particularly in patients with HIV infection or haematological cancer. Other chronic conditions (including, among others, congenital forms of immune deficiency, renal disease and heart disease), however, showed non-significant increases in risk compared with controls. This led the authors of one study to suggest that frailty and susceptibility to disease in general, leading to frequent hospital contacts, may be as strong a predictor of IPD as a stabilised specific underlying condition ³².

The main strength of this review is the use of broad inclusion criteria relating to clinical outcomes. Limitations of the review include the predefined risk conditions, which might lead to exclusion of some risk conditions such as hydrocephalus. The studies included were very different in terms of study periods and study methods (survey, surveillance database and cohort studies), providing a very wide range of results. Precaution should be taken when interpreting and comparing these results. Definitions of conditions implying an increased risk for pneumococcal infections and some of the individual risk categories vary between publications. Thus, physicians should refer to their local guidelines and national immunisation recommendations.

In conclusion, data on the incidence of IPD in children with underlying medical conditions are limited, and much research is needed in this area to determine the risk of disease, particularly in the post-PCV period. The data available, however, clearly show a substantial incidence of IPD in at-risk children, particularly those who are immunocompromised; there is also a corresponding significant increase in risk compared with healthy children.

Recently, PCV-13 became available for the prevention of IPD, pneumonia and acute otitis media in children 6 weeks to 17 years of age, and for the prevention of IPD in adults > 50 years of age ¹³. Furthermore, a number of European countries are recommending the use of PCVs in individuals with underlying diseases or conditions. Current vaccination recommendations aim to protect against the maximum number of serotypes by combining PCV-13 with PPV-23 ⁵,¹⁹. Further research is needed, however, to understand the benefits of PCVs and the optimal vaccination schedule in this population. After implementation of vaccination programmes, surveillance remains of the utmost importance to our understanding of how the risk of disease and the causative serotypes evolve.

Acknowledgments

The authors take full responsibility for the content of this article and thank Neostar Communications Limited, Oxford, UK (supported by Pfizer, France), for their assistance in preparing the manuscript, including preparing the first draft in close collaboration with the authors and the collation of author comments. Medical writing support was funded by Pfizer Pharmaceuticals, France. Employees of Pfizer Ltd, UK, and Pfizer Pharmaceuticals, France, were involved in the design, drafting, review and approval of the manuscript, and are listed as full authors.

Author contributions

All authors were involved in the concept/design of the review, analysis of the data, and drafting, critical review and approval of the manuscript.

Supplementary Material

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References

O'Brien KL, Wolfson LJ, Watt JP, et al., authors. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009;374:893–902. [PubMed]

World Health Organisation. Pneumococcal vaccines. WHO position paper - 2012. Wkly Epidemiol Rec. 2012;87:129–44. [PubMed]

De Carvalho Gomes H, Muscat M, Monnet DL, Giesecke J, Lopalco PL, authors. Use of seven-valent pneumococcal conjugate vaccine (PCV7) in Europe, 2001-2007. Euro Surveill. 2009;14:. . pii: 19159.

McClure CA, Ford MW, Wilson JB, Aramini JJ, authors. Pneumococcal conjugate vaccination in Canadian infants and children younger than five years of age: recommendations and expected benefits. Can J Infect Dis Med Microbiol. 2006;17:19–26. [PubMed]

Nuorti JP, Whitney CG, authors. Prevention of pneumococcal disease among infants and children - use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine - recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59:1–18. [PubMed]

Desai S, McGeer A, Quach-Thanh C, Elliott D, authors. . An advisory committee statement, National Advisory Committee on Immunization (NACI): update on the use of conjugate pneumococcal vaccines in childhood. Canadian Communicable Disease Report 2010. http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/10vol36/acs-12/acs-12-eng.pdf (accessed April 2013).

Whitney CG, Farley MM, Hadler J, et al., authors. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003;348:1737–46. [PubMed]

Poehling KA, Talbot TR, Griffin MR, et al., authors. Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine. JAMA. 2006;295:1668–74. [PubMed]

Gladstone RA, Jefferies JM, Faust SN, Clarke SC, authors. Continued control of pneumococcal disease in the UK - the impact of vaccination. J Med Microbiol. 2011;60:1–8. [PubMed]

Isaacman DJ, McIntosh ED, Reinert RR, authors. Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: impact of the 7-valent pneumococcal conjugate vaccine and considerations for future conjugate vaccines. Int J Infect Dis. 2010;14:e197–209. [PubMed]

Hanquet G, Lernout T, Vergison A, et al., authors. Impact of conjugate 7-valent vaccination in Belgium: addressing methodological challenges. Vaccine. 2011;29:2856–64. [PubMed]

GlaxoSmithKline UK. Synflorix Suspension for Injection in Pre-filled Syringe. 2012. Uxbridge: GlaxoSmithKline Biologicals SA;

Pfizer Limited. Prevenar 13 Suspension for Injection. 2012. Sandwich: Pfizer Limited;

European Medicines Agency. . Prevenar 13 http://www ema europa eu/ema/index jsp?curl=pages/medicines/human/medicines/001104/smops/Positive/human_smop_000452 jsp&mid=WC0b01ac058001d127 2012 (accessed February 2013).

Sanofi Pasteur MSD Limited. Pneumovax II. 2011. Maidenhead: Sanofi Pasteur MSD Limited;

American Academy of Pediatrics Committee on Infectious Diseases. Recommendations for the prevention of Streptococcus pneumoniae infections in infants and children: use of 13-valent pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23). Pediatrics. 2010;126:186–90. [PubMed]

National Immunisation Advisory Committee. Pneumococcal infection. Immunisation Guidelines for Ireland. 2010. Dublin: Royal College of Physicians Ireland;

Saxon State Ministry for Social Affairs and Consumer Protection. Empfehlungen der Sächsischen Impfkommission zur Durchführung von Schutzimpfungen im Freistaat Sachsen. 2012. Dresden: Saxon State Ministry for Social Affairs and Consumer Protection;

Conseil Supérieur de la Santé. Enfants à risque accru d'infections invasives à pneumocoques. Guide de Vaccination. 2013. Brussels: Conseil Supérieur de la Santé;

Rozenbaum MH, van Hoek AJ, Fleming D, Trotter CL, Miller E, Edmunds WJ, authors. Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine: economic analysis. BMJ. 2012;345:e6879 [PubMed]

Rozenbaum MH, van Hoek AJ, Fleming D, Trotter CL, Miller E, Edmunds WJ, authors. Correction to Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine: economic analysis. BMJ. 2012;345:e7437

van Hoek AJ, Andrews N, Waight PA, et al., authors. The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England. J Infect. 2012;65:17–24. [PubMed]

Thomas HJ, Wotton CJ, Yeates D, Ahmad T, Jewell DP, Goldacre MJ, authors. Pneumococcal infection in patients with coeliac disease. Eur J Gastroenterol Hepatol. 2008;20:624–8. [PubMed]

Steenhoff AP, Wood SM, Rutstein RM, Wahl A, McGowan KL, Shah SS, authors. Invasive pneumococcal disease among human immunodeficiency virus-infected children, 1989-2006. Pediatr Infect Dis J. 2008;27:886–91. [PubMed]

Adamkiewicz TV, Silk BJ, Howgate J, et al., authors. Effectiveness of the 7-valent pneumococcal conjugate vaccine in children with sickle cell disease in the first decade of life. Pediatrics. 2008;121:562–9. [PubMed]

Halasa NB, Shankar SM, Talbot TR, et al., authors. Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis. 2007;44:1428–33. [PubMed]

Poehling KA, Light LS, Rhodes M, et al., authors. Sickle cell trait, hemoglobin C trait, and invasive pneumococcal disease. Epidemiology. 2010;21:340–6. [PubMed]

Tran L, Hebert D, Dipchand A, Fecteau A, Richardson S, Allen U, authors. Invasive pneumococcal disease in pediatric organ transplant recipients: a high-risk population. Pediatr Transplant. 2005;9:183–6. [PubMed]

Melegaro A, Edmunds WJ, Pebody R, Miller E, George R, authors. The current burden of pneumococcal disease in England and Wales. J Infect. 2006;52:37–48. [PubMed]

Biernath KR, Reefhuis J, Whitney CG, et al., authors. Bacterial meningitis among children with cochlear implants beyond 24 months after implantation. Pediatrics. 2006;117:284–9. [PubMed]

Wilson-Clark SD, Squires S, Deeks S, authors. Bacterial meningitis among cochlear implant recipients–Canada, 2002. MMWR Morb Mortal Wkly Rep. 2006;55(Suppl 1):20–4. [PubMed]

Hjuler T, Wohlfahrt J, Staum KM, Koch A, Biggar RJ, Melbye M, authors. Risks of invasive pneumococcal disease in children with underlying chronic diseases. Pediatrics. 2008;122:e26–32. [PubMed]

Pilishvili T, Zell ER, Farley MM, et al., authors. Risk factors for invasive pneumococcal disease in children in the era of conjugate vaccine use. Pediatrics. 2010;126:e9–17. [PubMed]

Meisel R, Toschke AM, Heiligensetzer C, Dilloo D, Laws HJ, von Kries R, authors. Increased risk for invasive pneumococcal diseases in children with acute lymphoblastic leukaemia. Br J Haematol. 2007;137:457–60. [PubMed]

Talbot TR, Hartert TV, Mitchel E, et al., authors. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med. 2005;352:2082–90. [PubMed]

Ludvigsson JF, Olen O, Bell M, Ekbom A, Montgomery SM, authors. Coeliac disease and risk of sepsis. Gut. 2008;57:1074–80. [PubMed]

Hjuler T, Wohlfahrt J, Simonsen J, et al., authors. Perinatal and crowding-related risk factors for invasive pneumococcal disease in infants and young children: a population-based case-control study. Clin Infect Dis. 2007;44:1051–6. [PubMed]

Haddad MB, Porucznik CA, Joyce KE, et al., authors. Risk factors for pediatric invasive pneumococcal disease in the Intermountain West, 1996-2002. Ann Epidemiol. 2008;18:139–46. [PubMed]

Hsu KK, Shea KM, Stevenson AE, Pelton SI, authors. Underlying conditions in children with invasive pneumococcal disease in the conjugate vaccine era. Pediatr Infect Dis J. 2011;30:251–3. [PubMed]

Bruce MG, Deeks SL, Zulz T, et al., authors. International Circumpolar Surveillance System for invasive pneumococcal disease, 1999-2005. Emerg Infect Dis. 2008;14:25–33. [PubMed]

Hennessy TW, Singleton RJ, Bulkow LR, et al., authors. Impact of heptavalent pneumococcal conjugate vaccine on invasive disease, antimicrobial resistance and colonization in Alaska Natives: progress towards elimination of a health disparity. Vaccine. 2005;23:5464–73. [PubMed]

Singleton RJ, Hennessy TW, Bulkow LR, et al., authors. 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. [PubMed]

Singleton RJ, Holman RC, Wenger J, et al., authors. Trends in hospitalization for empyema in Alaska Native children younger than 10 years of age. Pediatr Infect Dis J. 2011;30:528–30. [PubMed]

Wenger JD, Zulz T, Bruden D, et al., authors. Invasive pneumococcal disease in Alaskan children: impact of the seven-valent pneumococcal conjugate vaccine and the role of water supply. Pediatr Infect Dis J. 2010;29:251–6. [PubMed]

Lacapa R, Bliss SJ, Larzelere-Hinton F, et al., authors. 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. [PubMed]

Millar EV, Pimenta FC, Roundtree A, et al., authors. Pre- and post-conjugate vaccine epidemiology of pneumococcal serotype 6C invasive disease and carriage within Navajo and White Mountain Apache communities. Clin Infect Dis. 2010;51:1258–65. [PubMed]

Weatherholtz R, Millar EV, Moulton LH, et al., authors. Invasive pneumococcal disease a decade after pneumococcal conjugate vaccine use in an American Indian population at high risk for disease. Clin Infect Dis. 2010;50:1238–46. [PubMed]

Hsu K, Pelton S, Karumuri S, Heisey-Grove D, Klein J, authors. Population-based surveillance for childhood invasive pneumococcal disease in the era of conjugate vaccine. Pediatr Infect Dis J. 2005;24:17–23. [PubMed]

Hsu KK, Shea KM, Stevenson AE, Pelton SI, authors. Changing serotypes causing childhood invasive pneumococcal disease: Massachusetts, 2001-2007. Pediatr Infect Dis J. 2010;29:289–93. [PubMed]

Garcia-Vidal C, Ardanuy C, Gudiol C, et al., authors. Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteremia in cancer patients. J Infect. 2012;65:621–7

Pessach I, Walter J, Notarangelo LD, authors. Recent advances in primary immunodeficiencies: identification of novel genetic defects and unanticipated phenotypes. Pediatr Res. 2009;65:3R–12

Wotton CJ, Goldacre MJ, authors. Risk of invasive pneumococcal disease in people admitted to hospital with selected immune-mediated diseases: record linkage cohort analyses. J Epidemiol Community Health. 2012;66:1177–81. [PubMed]

Pilishvili T, Lexau C, Farley MM, et al., authors. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 2010;201:32–41. [PubMed]

Tan TQ, author. Pediatric invasive pneumococcal disease in the United States in the era of pneumococcal conjugate vaccines. Clin Microbiol Rev. 2012;25:409–19. [PubMed]

van Hoek AJ, Andrews N, Waight PA, George R, Miller E, authors. Effect of serotype on focus and mortality of invasive pneumococcal disease: coverage of different vaccines and insight into non-vaccine serotypes. PLoS ONE. 2012;7:e39150 [PubMed]

Byington CL, Korgenski K, Daly J, Ampofo K, Pavia A, Mason EO, authors. Impact of the pneumococcal conjugate vaccine on pneumococcal parapneumonic empyema. Pediatr Infect Dis J. 2006;25:250–4. [PubMed]

Shouval DS, Greenberg D, Givon-Lavi N, Porat N, Dagan R, authors. Site-specific disease potential of individual Streptococcus pneumoniae serotypes in pediatric invasive disease, acute otitis media and acute conjunctivitis. Pediatr Infect Dis J. 2006;25:602–7. [PubMed]

Ruckinger S, von KR, Siedler A, van der LM, authors. Association of serotype of Streptococcus pneumoniae with risk of severe and fatal outcome. Pediatr Infect Dis J. 2009;28:118–22. [PubMed]

European Antimicrobial Resistance Surveillance System. EARSS Annual Report. 2008. Bilthoven: EARSS;

Giannattasio A, Squeglia V, Lo Vecchio A, et al., authors. Pneumococcal and influenza vaccination rates and their determinants in children with chronic medical conditions. Ital J Pediatr. 2010;36:28 [PubMed]

Shankar A, Samraj R, Aiyedun V, Janda M, Ramaiah S, authors. General practitioners' perceptions on pneumococcal vaccination for children in United Kingdom. Hum Vaccin. 2009;5:177–80. [PubMed]

Badertscher N, Morell S, Rosemann T, Tandjung R, authors. General practitioners' experiences, attitudes, and opinions regarding the pneumococcal vaccination for adults: a qualitative study. Int J Gen Med. 2012;5:967–74. [PubMed]

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Table 1.

Risk categories for invasive pneumococcal disease included in the review*

Immunocompetent at-risk groups
Immunocompromised at-risk groups

Chronic/cyanotic heart disease

Chronic liver disease

Chronic renal disease

Chronic respiratory disease (e.g. cystic fibrosis)

Chronic lung disease/bronchopulmonary dysplasia

Chronic/severe asthma

Recurrent pulmonary infections

Preorgan-transplant patients

CNS malformations, cerebrospinal leaks, liquor shunts

Cochlear implant recipients

Metabolic disease (e.g. diabetes)

Coeliac disease

Care home residents/permanent institutionalisation because of illness

Smoking/exposure

Prematurity

Congenital or primary immunodeficiency (e.g. agammaglobulinemia, SCID, CVID, complement deficiency [particularly early component deficiencies: C1, C2, C3, C4])

Secondary immunodeficiency (e.g. HIV)

Bone marrow, haematopoietic stem cell and solid organ transplant recipients

Neoplastic diseases (HL, NHL, lymphomas, leukaemias, other diseases of the blood-forming organs)

Asplenia or dysfunction of the spleen, including sickle-cell disease

Iatrogenic immunosuppression

Chromosomal aberration (e.g. Down's syndrome)

Nephrotic disease

*. Definition of some individual risk categories (e.g. chronic/severe asthma) may vary between publications and between guidelines.

CNS, central nervous system; CVID, common variable immunodeficiency; HIV, human immunodeficiency virus; HL, Hodgkin lymphoma; IPD, invasive pneumococcal disease; NHL, non-Hodgkin lymphoma; SCID, severe combined immunodeficiency.

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Figure 1.

Results of literature search and evaluation of identified studies according to Preferred Reporting Terms for Systematic Reviews and Meta-Analyses

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Table 2.

Incidence of general invasive pneumococcal disease in children

Citation (country) | Methodology | Age range (years [median]) | N * | Time period | Incidence (per 100,000 patient-years)
Asplenia/splenic dysfunction
 van Hoek 2012 (UK) 22 | National GP database study | 2–15 [–] | 11 | 08–09 | 19
Chronic heart disease
 van Hoek 2012 (UK) 22 | National GP database study | 2–15 [–] | 48 | 08–09 | 16
Chronic renal disease
 van Hoek 2012 (UK) 22 | National GP database study | 2–15 [–] | 33 | 08–09 | 46
Chronic liver disease
 van Hoek 2012 (UK) 22 | National GP database study | 2–15 [–] | 9 | 08–09 | 117
Chronic respiratory disease
 van Hoek 2012 (UK) 22 | National GP database study | 2–15 [–] | 19 | 08–09 | 50
Coeliac disease
 Thomas 2008 (UK) 23 | Regional hospitalisation database | < 15 [–] | ∽2200 | 63–03 | 113†
Diabetes
 van Hoek 2012 (UK) 22 | National GP database study | 2–15 [–] | 9 | 08–09 | 15
HIV infection
 Steenhoff 2008 (PA, USA) 24 | Retrospective cohort study | 0.2–16.8 [6.3] | 20 | 89–06 | 1200
89–95 | 1862
1996 | 2128
97–99 | 292
2000 | 3101
01–06 | 860
0.2–< 5 [–] | – | 89–95 | 2174
1996 | 2273
97–99 | 0
2000 | 0
01–06 | 1724
5–16.8 [–] | – | 89–95 | 1000
1996 | 2000
97–99 | 444
2000 | 4167
01–06 | 716
 van Hoek 2012 (UK) 22 | National GP database study | 2–15 [–] | 6 | 08–09 | 398
Immunosuppression
 van Hoek 2012 (UK) 22 | National GP database study‡ | 2–15 [–] | 174 | 08–09 | 162
Sickle-cell disease
 Adamkiewicz 2008 (GA, USA) 25 | Surveillance database study | ≤10 [–] | 1247 | 95–99 | 170
2000 | 140
2001 | 70
2002 | 40
 Halasa 2007 (TN, USA) 26 | Database (Medicaid) study | < 5 [–] | 21 | 95–99 | 2044
2000 | 1077
01–04 | 134
< 2 [–] | 16 | 95–99 | 3630
2000 | 3012
01–04 | 335
 Poehling 2010 (TN, USA) 27 | State-managed healthcare database study (Hb S or C trait) | < 5 [–] | 38 | 96–05 | 139.8
21 | 96–00 | 260.8
7 | 01–05 | 46.0
State-managed healthcare database study (Hb S trait) | < 5 [–] | 30 | 96–05 | 142.6
19 | 96–00 | 300.9
3 | 01–05 | 25.6
State-managed healthcare database study (Hb C trait) | < 5 [–] | 8 | 96–05 | 130.1
2 | 96–00 | 115.0
4 | 01–05 | 113.7
Transplant recipients
 Tran 2005 (ON, Canada) 28 | Retrospective single-centre study | < 5 [–] | 522 | 90–01 | 176
General high-risk patients
 Melegaro 2006 (UK) 29 | National hospital database study§ | < 1 month [–] | – | 95–00 | 75.3
1–11 months [–] | 38.6
1–4 [–] | 11.6
5–9 [–] | 2
10–14 [–] | 1
 van Hoek 2012 (UK) 22 | National GP database study¶ | 2–15 [–] | 261 | 08–09 | 46

*. Total number of patients in analysis.

†. Based on 3.4 cases per 1000 patients over median follow-up of 3 years.

‡. Includes those who are immunocompromised by disease, such as HIV or leukaemia, asplenia or splenic dysfunction.

§. ‘High risk’ defined as diabetes mellitus, chronic renal, hepatic or pulmonary disease, neoplastic disease, chronic immunosuppression.

¶. ‘High risk’ defined as asplenia/splenic dysfunction (including sickle-cell disease and coeliac syndrome), chronic renal, hepatic, heart or respiratory disease (including organ transplantation), diabetes mellitus, immunosuppression (including HIV, leukaemia and bone marrow transplantation), cochlear implants and cerebrospinal fluid leaks.

GP, general practitioner; Hb, haemoglobin; HIV, human immunodeficiency virus.

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Table 3.

Incidence of specific forms of invasive pneumococcal disease in children

Citation (country) | Methodology | Risk category | Age range (years [median]) | N * | Time period | Incidence (per 100,000 patient-years)
Meningitis
 Biernath 2006 (USA) 30 | Cohort study | Cochlear implants | < 6 [55 months] | 4265 | 97–04 | 120
 Wilson-Clark 2006 (Canada) 31b | Postal survey | Cochlear implants | <18 [–] | 482 | 95–02 | 290
<6 [–] |  |
< 18 [–] | – | 95–98 | 220
99–02 | 400
< 6 [–] | – | 95–98 | 150
99–02 | 310
 Melegaro 2006 (UK) 29 | National hospital database study † | General high-risk patients | < 1 month [–] | – | 95–00 | 15.6
1–11 months [–] | 15.3
1–4 [–] | 1.7
5–9 [–] | 0.2
10–14 [–] | 0.2
Bacteraemia
 Steenhoff 2008 (PA, USA) 24 | Retrospective cohort study | HIV infection | – | – | 08–09 | 398

*. Total number of patients in analysis.

†. Includes some bacterial meningitis cases related to Neisseria meningitidis or of unknown bacterial type.

HIV, human immunodeficiency virus.

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Table 4.

Risk of IPD in children

Citation (country) | Methodology | Clinical manifestation | Age range (years) | N | Time period | Comparator children | Risk (95% CI)
Chronic organ disease
 Heart disease
  Hjuler 2008 (Denmark) 32 | Surveillance database study (all heart disease) | IPD | 0–17 | – | 1977–2005 | Children with no chronic diseases | aRR = 2.4 (1.6–3.4)
Surveillance database study (chronic heart disease) | 14 | aRR = 3.6 (1.4–9.6)
Surveillance database study (congenital heart disease†) | 67 | aRR = 2.0 (1.4–3.1)
  Pilishvili 2010 (USA) 33 | Surveillance study | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 3.5 (2.1–5.7) ***
  van Hoek 2012 (UK) 22 | National GP database study | IPD | 2–15 | 48 | 2008–2009 | No risk factors for IPD | OR = 4.1 (3.1–5.5)
 Liver disease
  van Hoek 2012 (UK) 22 | National GP database study | IPD | 2–15 | 9 | 2008–2009 | No risk factors for IPD | OR = 29.6 (15.3–57.2)
 Lung disease
  Hjuler 2008 (Denmark) 32 | Surveillance database study (all lung disease) | IPD | 0–17 | – | 1977–2005 | Children with no chronic diseases | aRR = 1.4 (1.0–1.9)
Surveillance database study (chronic airway disease) | 25 | aRR = 4.1 (2.1–7.9)
Surveillance database study (asthma) | 60 | aRR = 1.1 (0.7–1.6)
Surveillance database study (congenital respiratory malformation) | 11 | aRR = 0.9 (0.4–1.9)
  Pilishvili 2010 (USA) 33 | Surveillance study (chronic lung condition) | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 3.5 (1.5–8.0) ***
Surveillance study (asthma) | OR = 1.8 (1.5–2.2) ***
  Talbot 2005 (USA) 35 | Nested case–control study (asthma) | IPD | 2–4 | 26 | 1995–2002 | Children without IPD | aOR = 2.3 (1.4–4.0)
5–17 | 11 | aOR = 4.0 (1.5–10.7)
  van Hoek 2012 (UK) 22 | National GP database study | IPD | 2–15 | 9 | 2008–2009 | No risk factors for IPD | OR = 12.7 (8.1–20.0)
 Renal disease
  Hjuler 2008 (Denmark) 32 | Surveillance database study (all renal disease) | IPD | 0–17 | – | 1977–2005 | Children with no chronic diseases | aRR = 4.1 (1.5–11.1)
Surveillance database study (chronic renal disease) | 6 | aRR = 18.9 (2.8–127.1)
Surveillance database study (congenital renal malformation) | 7 | aRR = 1.6 (0.4–6.3)
  Pilishvili 2010 (USA) 33 | Surveillance study (kidney disease [no dialysis]) | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 3.6 (1.1–11.4) *
Surveillance study (nephrotic syndrome or renal failure) | OR = 14.7 (2.9–76) **
  van Hoek 2012 (UK) 22 | National GP database study | IPD | 2–15 | 33 | 2008–2009 | No risk factors for IPD | OR = 11.7 (8.3–16.6)
Gastrointestinal disease
  Hjuler 2008 (Denmark) 32 | Surveillance database study (all gastrointestinal disease) | IPD | 0–17 | – | 1977–2005 | Children with no chronic diseases | aRR = 1.5 (0.9–2.4)
Surveillance database study (oesophageal disease) | 8 | aRR = 1.1 (0.4–3.5)
Genetic disease/congenital malformation
 Hjuler 2008 (Denmark) 32 | Surveillance database study (all genetic disease) | IPD | 0–17 | – | 1977–2005 | Children with no chronic diseases | aRR = 2.1 (1.1–4.1)
Surveillance database study (chromosomal abnormalities) | 22 | aRR = 2.5 (1.1–5.6)
Surveillance database study (inborn error of metabolism) | 5 | aRR = 1.1 (0.3–4.1)
Surveillance database study (congenital gut malformation‡) | 35 | aRR = 1.7 (1.0–2.9)
Surveillance database study (congenital CNS malformation§) | 23 | aRR = 2.9 (1.4–6.2)
Surveillance database study (cerebral palsy) | 18 | aRR = 1.2 (0.5–3.0)
 Pilishvili 2010 (USA) 33 | Surveillance study (congenital/developmental disorders) | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 4.9 (3.0–8.0) ***
Immunosuppression
 Asplenia/splenic dysfunction/splenectomy
  Hjuler 2008 (Denmark) 32 | Surveillance database study | IPD | 0–17 | 6 | 1977–2005 | Children without invasive surgery | aRR = 14.4 (1.3–154.2)
  Pilishvili 2010 (USA) 33 | Surveillance study | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 3.9 (0.6–23.5)
  van Hoek 2012 (UK) 22 | National GP database study | IPD | 2–15 | 11 | 2008–2009 | No risk factors for IPD | OR = 4.7 (2.6–8.5)
 Coeliac disease
  Ludvigsson 2008 (Sweden) 36 | Cohort study | Sepsis | 0–15 | – | 1964–2003 | General population | HR = 3.4 (1.1–10.6)
 HIV infection
  van Hoek 2012 (UK) 22 | National GP database study | IPD | 2–15 | 6 | 2008–2009 | No risk factors for IPD | OR = 100.8 (44.7–227.2)
 Immunological/metabolic disease
  Hjuler 2008 (Denmark) 32 | Surveillance database study (all immunological/metabolic disease) | IPD | 0–17 | – | 1977–2005 | Children with no chronic diseases | aRR = 2.0 (0.9–4.2)
Surveillance database study (haemolytic anaemia) | 3 | aRR = 2.9 (0.6–13.8)
Surveillance database study (autoimmune disease) | 5 | aRR = 2.6 (0.6–10.7)
Surveillance database study (congenital immune deficiency) | 12 | aRR = 1.4 (0.4–4.8)
Surveillance database study (diabetes) | 1 | aRR = 0.4 (0.0–14.8)
 Immunosuppression
  Pilishvili 2010 (USA) 33 | Surveillance study (any immunocompromising condition) | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 4.9 (3.4–6.9) ***
Surveillance study (HIV or immune system disorder) | OR = 14.5 (5.7–36.8) ***
Surveillance study (systemic steroid use) | OR = 2.2 (1.6–3.0) ***
  van Hoek 2012 (UK)22 | National GP database study | IPD | 2–15 | 174 | 2008–2009 | No risk factors for IPD | OR = 41.0 (35.0–48.0)
 Sickle-cell disease
  Pilishvili 2010 (USA)33 | Surveillance study | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 5.6 (1.6–19.4) **
  Poehling 2010 (TN, USA)27 | State-managed healthcare database study | IPD (Hb S or C trait) | < 5 [–] | 66 | 1996–2005 | White, with normal Hb | RR = 1.77 (1.22–2.55)
IPD (Hb S trait) | 52 | RR = 1.80 (1.20–2.69)
IPD (Hb C trait) | 14 | RR = 1.66 (0.81–3.39)
 Transplant recipients
  Hjuler 2008 (Denmark)32 | Surveillance database study | IPD | 0–17 | 18 | 1977–2005 | Children without invasive surgery | aRR = 14.3 (3.0–68.2)
  Tran 2005 (ON, Canada)28 | Retrospective single-centre study | IPD | < 5 [–] | 522 | 1990–2001 | All < 2 years | p = 0.13 (no RR or OR specified)
All < 5 years | p < 0.001 (no RR or OR specified)
Neoplastic diseases
 Hjuler 2008 (Denmark)32 | Surveillance database study (all cancers) | IPD | 0–17 | – | 1977–2005 | Children with no chronic diseases | aRR = 19.0 (8.7–41.5)
Surveillance database study (haematological cancers) | 44 | aRR = 52.1 (13.7–198.2)
Surveillance database study (non-haematological cancers) | 19 | aRR = 8.9 (3.1–26.1)
 Meisel 2007 (Germany)34 | Surveillance database study (acute lymphoblastic leukaemia) | IPD | 0–4 | 5 | 1997–2003 | General population | SIR = 7.6 (2.8–17.0) ***
5–9 | 4 | SIR = 50.6 (16.1–122.1) ***
0–14 | 9 | SIR = 11.4 (5.6–20.9) ***
 Pilishvili 2010 (USA)33 | Surveillance study (any cancer) | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 78.0 (10.2–593) ***
 Thomas 2008 (UK)23 | Regional hospitalisation database | IPD | 0–15 | – | 1963–2003 | General population | Rate ratio = 1.39 (0.51–3.03)
Neurological disease
 Hjuler 2008 (Denmark)32 | Surveillance database study (all neurological disease) | IPD | 0–17 | – | 1977–2005 | Children with no chronic diseases | aRR = 2.5 (1.7–3.6)
Surveillance database study (epilepsy¶) | 37 | aRR = 2.5 (1.5–4.2)
Surveillance database study (hydrocephalus) | 17 | aRR = 1.0 (0.4–2.4)
Prematurity ††
 Hjuler 2007 (Denmark)37 | Multiple database study‡‡ | IPD | 0–< 0.5 | 22 | 1980–2005 | Gestational age 37–42 weeks | aRR = 2.59 (1.39–4.82)
0.5–< 2 | 81 | aRR = 1.54 (1.18–2.02)
2–5 | 22 | aRR = 1.31 (0.79–2.18)
Tobacco exposure
 Haddad 2008 (USA intermountain west)38 | Telephone survey | IPD | < 1 | 4 | 1996–2002 | Children without IPD | OR = 0.6 (0.2–2.0)
1–< 2 | 6 | OR = 1.8 (0.4–7.7)
2–< 5 | 5 | OR = 2.6 (0.4–15.3)
5–16 | 5 | OR = 1.2 (0.3–4.6)
 Pilishvili 2010 (USA)33 | Surveillance study (household exposure to smoking) | IPD | 3 months–< 5 years | – | 2001–2004 | No tobacco exposure | OR = 1.4 (1.2–1.7) ***
Surveillance study (> 20 cigarettes/day) | OR = 1.7 (1.2–2.4) ***
Surveillance study (11–20 cigarettes/day) | OR = 0.9 (0.6–1.3)
Surveillance study (1–10 cigarettes/day) | OR = 1.7 (1.3–2.2) ***
General high-risk patients
 Haddad 2008 (USA intermountain west)38 | Telephone survey§§ | IPD | 0–16 | 32 | 1996–2002 | Children without IPD | 32 of 120 cases vs. 1 of 156 controls (no RR or OR specified)
 Hjuler 2008 (Denmark)32 | Surveillance database study (all chronic diseases¶¶) | IPD | 0–17 | 744 | 1977–2005 | Children with no chronic diseases | aRR = 2.4 (2.0–2.9)
Surveillance database study (all chronic diseases excluding high-risk groups†††) | – | aRR = 2.1 (1.7–2.6)
 Hsu 2011 (MA, USA)39 | Surveillance database study‡‡‡ | IPD | 0–17 | 14 | 2001–2002 | Children with no known risk conditions | –
0–17 | 23 | 2002–2003 | aOR = 1.5 (0.7–3.3)
0–17 | 11 | 2003–2004 | aOR = 0.9 (0.4–2.1)
0–17 | 20 | 2004–2005 | aOR = 1.6 (0.7–3.5)
0–17 | 14 | 2005–2006 | aOR = 0.8 (0.4–1.9)
0–17 | 13 | 2006–2007 | aOR = 0.6 (0.3–1.5)
5–17 | 39 | 2001–2007 | aOR = 2.8 (1.8–4.5)
 Pilishvili 2010 (USA)33 | Surveillance study§§§ | IPD | 3 months–< 5 years | – | 2001–2004 | Children without IPD | OR = 3.3 (2.4–4.5) ***
 van Hoek 2012 (UK)22 | National GP database study¶¶¶ | IPD | 2–15 | 261 | 08–09 | No risk factors for IPD | OR = 11.7 (10.2–13.3)

*. p < 0.05; **p < 0.01; ***p < 0.001.

†. Septal heart defects contributed to 40%.

‡. Major contributors were biliary atresia (26%) and oesophageal atresia (20%).

§. Major contributors were cerebral cysts (20%), microcephalus (20%) and congenital hydrocephalus (20%).

¶. Concomitant chronic neurological disease in 43%.

††. ‘Prematurity’ defined as gestational age 19–36 weeks.

‡‡. Databases include national Streptococcus, civil registration, childcare, birth, patient and labour market databases.

§§. ‘High risk’ defined as any underlying chronic illness (including cancer, asplenia, lupus, renal failure, liver disease, congenital heart disease, immunosuppressive therapy to prevent transplant rejection, and CNS disorders characterised by severe developmental delay, failure to thrive, or craniofacial structural abnormalities).

¶¶. The total number is lower than the number of specific chronic diseases because patients may have > 1 of the specific chronic diseases.

†††. Excluding children with cancer, chronic renal disease, splenectomy or transplantation; not adjusted for specific chronic diseases.

‡‡‡. ‘High-risk’ defined as sickle-cell disease, congenital or acquired asplenia or splenic dysfunction, HIV infection, cochlear implants, congenital immune deficiency, diseases associated with immunosuppressive therapy or radiation therapy, chronic cardiac disease, chronic pulmonary disease, chronic renal insufficiency, cerebrospinal leaks from congenital malformation, skull fracture or neurological procedure, diabetes mellitus, premature birth (< 38 weeks) or low birth weight (< 2500 g).

§§§. ‘High risk’ defined as any chronic disease.

¶¶¶. ‘High risk’ defined as asplenia/splenic dysfunction (including sickle-cell disease and coeliac syndrome), chronic renal, hepatic, heart or respiratory disease (including organ transplantation), diabetes mellitus, immunosuppression (including HIV, leukaemia and bone marrow transplantation), cochlear implants and cerebrospinal fluid leaks.

aOR, adjusted odds ratio; aRR, adjusted rate ratio; CI, confidence interval; CNS, central nervous system; GP, general practitioner; Hb, haemoglobin; HIV, human immunodeficiency virus; HR, hazard ratio; IPD, invasive pneumococcal disease; OR, odds ratio; RR, relative risk; SIR, standardised incidence ratio.

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