Streptococcus pneumoniae was first identified over 100 years ago, yet today pneumococcal disease continues to challenge clinicians due to the morbidity and mortality associated with it. 

For this reason, it is important for us to update our understanding on pneumococcal disease in Ireland and the issues surrounding vaccination to prevent it.

Continuing burden of pneumococcal disease

Pneumococcal infections can be divided into invasive (IPD) and non-invasive pneumococcal disease. IPD covers the life-threatening conditions of pneumococcal sepsis, meningitis and pneumonia, while non-invasive pneumococcal disease includes the more common pneumococcal infections of otitis media, sinusitis and bronchitis.

In 2000, the WHO estimated that pneumococcal disease resulted in 14.5 million serious infections and 735,000 deaths each year in HIV-negative children under five years of age.¹ In Ireland:

• IPD had an incidence in 2010 of 9.2/100,000 population, with the incidence rising dramatically at the extremes in age to: 18.9/100,000 in children under two years old; 28.2/100,000 in 65-74-year-olds; 48.3/100,000 in 75-84-year-olds; and 106.2/100,000 in over-85-year-olds²
• Pneumococcal pneumonia remains the leading cause of community-acquired pneumonia, affecting one in 1,000 adults a year with a fatality rate of 7%
• Pneumococcal meningitis affects about one in 100,000 people annually and has a mortality rate of 11-16%, with 15-20% of survivors having long-term central nervous system sequelae and a further 10% at least having permanent hearing impairment.³

The immune response: who is at risk?

Virulent S. pneumoniae serotypes have thick polysaccharide capsules which protect against the immune response. There are over 90 serotypes, or strains, of pneumococcus, which all differ in the polysaccharide composition of their capsules, resulting in individuals only being immune to the specific serotypes that they have previously been infected with or vaccinated against. Two key weapons in the immune response to pneumococcus are: firstly, anti-pneumococcal polysaccharide antibodies, which can stick to the capsule; and, secondly, the spleen, which helps to eradicate the pneumococcus bacteria.

Individuals at the extremes of age or who are immunocompromised may not make adequate levels of anti-pneumococcal antibodies and therefore have a higher risk of developing IPD. 

In infancy we acquire the ability to make antibodies to most antigens in the first six months of life, but we are slower to develop the capacity to make antibodies against polysaccharide antigens. 

Children under two years of age are at an increased risk of developing pneumococcal disease and, as is discussed later, children under five years of age have been shown to have poor responses to polysaccharide antigen vaccines.  

Individuals with asplenia and splenic dysfunction are also particularly susceptible to infection with pneumococcus and other encapsulated bacteria.

For structural reasons, individuals with cochlear implants, skull fractures, intracranial shunts and cerebrospinal fluid (CSF) leaks have a higher risk of developing pneumococcal meningitis and sepsis.  

Current Irish guidelines for at-risk groups recommended for pneumococcal vaccination are shown in Table 1.³

Rationale for pneumococcal vaccine choice

There are currently two types of pneumococcal vaccine available: the pneumococcal polysaccharide vaccine (PPV [Pneumovax 23]) and the pneumococcal conjugate vaccine (PCV [Prevenar]).

PPV is against capsular polysaccharide antigens from 23 serotypes of pneumococcus that are responsible for 90% of IPD in Ireland.³ A single dose of PPV is recommended for all individuals at risk for IPD over 17 years of age, and for all individuals over 64 years of age. 

PPV is an effective vaccine for preventing invasive pneumococcal infection that has been available for over 30 years, which raises the question of why an alternative pneumococcal vaccine should ever be considered?  

As discussed previously (because of the slow development of the ability to produce anti-polysaccharide antibodies compared to other antigens such as proteins), infants are at an increased risk of developing IPD, and children under five years of age will not make adequate antibody responses to polysaccharide-based vaccines, including PPV. 

PCV and other conjugated vaccines enhance the child’s ability to make anti-polysaccharide antibodies by conjugating or linking the polysaccharide antigens to proteins. 

Therefore, PCV is recommended to all children under two years of age and at-risk children under 18 years of age.  

PCV was added to the Irish routine primary immunisation schedule in September 2008 and is given as three doses at two, four and 12 months of age. The first PCV (PCV7) recommended was against the seven serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) responsible in 2008 for at least 90% of IPD in Irish children. 

Between 2007 and 2010, the impact of PCV7 in Ireland was a 20.3% drop of IPD in all age groups, with a 59.2% drop of IPD in children under two years of age.⁴

The introduction of PCV7 into the childhood immunisation schemes of the UK (2006) and US (2000) has also resulted in a drop in the IPD rate in the unvaccinated adult population, though this has not been seen in Ireland to date.⁵

Serotype replacement

Introduction of PCV7 into the primary immunisation scheme in 2008 also resulted in a change in prevalence of Irish pneumococcal serotypes. There has been a predictable increase in serotypes not covered by PCV7, such as 19A and 8, and a decrease in serotypes included in the vaccine.⁴

In 2010, PVC7 was replaced in the immunisation schedule by a 13-valent pneumococcal conjugate vaccine (PCV13), or Prevenar 13. 

This new vaccine covers an additional six pneumococcal serotypes (1, 3, 5, 6A, 7F, 19A), including the prevalent 7F and 19A serotypes, and is estimated to cover 90% of the serotypes currently causing IPD in Irish children of less than two years of age.  

Controlling antimicrobial resistance

Penicillins, cephalosporins and macrolides are first-line treatment for pneumococcal disease. Pneumococcal antimicrobial resistance was first reported in 1967 and by 1999 19% of IPD isolates in Ireland were due to penicillin non-susceptible pneumococcus (PNSP).⁶

The introduction of PPV pneumococcal vaccination and increased antibiotic prudence saw penicillin resistance drop to 10.3% of IPD isolates by 2004. 

Unfortunately, by 2008 there was once again an increase in penicillin resistance, with 23.1% of IPD isolates being penicillin-resistant.⁶ The rise in antimicrobial resistance has been most dramatic in serotypes not covered by the PCV7, particularly serotype 19A.  

As PCV13 does protect against serotype 19A it is expected that the introduction of PCV13 will lead to a reduction in the prevalence of antimicrobial-resistant pneumococcus. The Centres for Disease Control and Prevention (CDC) estimate that PCV13 will cover 97% of penicillin-resistant IPD infections in the US.⁷

The most recent published data from 2011 are encouraging, with some reduction in antimicrobial-resistant isolates, as 15.2% of IPD-causing serotypes were resistant to penicillin and 13.3% were erythromycin-resistant in Ireland.²

Summary and key points

Pneumococcal disease continues to be a major cause of morbidity and mortality in Ireland, especially in infants and older individuals. 

Pneumococcal vaccines are very effective for preventing pneumococcal disease and should be administered as per Irish Immunisation guidelines.

Since 2010, the PCV recommended in the primary immunisation scheme has been changed from the 7-valent PCV7 to 13-valent PCV13. 

PCV13 covers an additional six serotypes and protects against the serotypes currently responsible for 90% of serious pneumococcal infection in infants. 

Smokers and alcoholics are now regarded as at risk for IPD and are recommended to receive the PPV23 pneumococcal vaccine.

Pneumococcal vaccination programmes reduce the prevalence of antimicrobial-resistant pneumococcal infections.

References

1. Hib and Pneumococcal morbidity and mortality estimates, WHO 2000. http://www.who.int/immunization_monitoring/burden/en/
2. Streptococcus pneumonia (Invasive), Vaccine Preventable Diseases.  Health Surveillance Protection Centre Annual Report 2010. Published 19 December 2011.  Chapter 1.8, pp 28-30
3. Immunisation Guidelines for Ireland 2008 edition, updated online September 2011.  National Immunisation Advisory Committee of the Royal College of Physicians of Ireland. Chapter 12, pp 125-135 http://www.immunisation.ie/en/Downloads/NIACGuidelines/PDFFile_15486_en.pdf
4. Fitzgerald M, Vickers I, O’Lorcain P et al. Decline in invasive pneumococcal disease in Ireland since introducing the 7 valent pneumococcal conjugate vaccine (PCV7). Heath Protection Surveillance Centre. Poster at Faculty of Public Health, Summer Scientific Meeting 25-25th May 2011
5. Kaye P, Malkani R, Martin S et al. Poster. Health Protection Agency Centre for Infections.  Invasive Pneumococcal Disease (IPD) in England and Wales after 7-valent pneumococcal conjugate vaccine (PCV7): potential impact of 10 and 13-valent vaccine
6. EARS-Net Report for Quarter 3 2011. Irish EARS Steering Group. HSE - HPSC. December 2011
7. Drug-resistant Streptococcus pneumonia Disease. Centre for Disease Control and Prevention. Department of Health and Human Services, USA.  http://www.cdc.gov/ncidod/dbmd/diseaseinfo/drugresisstreppneum_t.htm