Despite good access to antibiotics, Streptococcus pneumoniae is still a significant cause of illness and death worldwide. S. pneumoniae causes several acute, invasive and noninvasive clinical infections; it is one of the leading causative agents in COPD exacerbations; and it is the most frequently detected pathogen responsible for community- acquired pneumonia (CAP). Pneumococcal pneumonia is accompanied by bacteraemia (bacteria in the blood) in 10–30% of cases.
S. pneumoniae is gaining resistance to the in vitro activity of several antimicrobial agents and, even if questions remain regarding the clinical impact of this phenomenon, increasing numbers of reports indicate that antibiotic resistance can lead to more treatment failures, if not higher mortality.
Reported incidence rates of invasive pneumococcal disease in European and US studies indicate an overall incidence of 11–23.2 per 100 000 people, rising to 16.2–59.7 per 100 000 in adults over 65 years of age. The studies in question were conducted between 1995 and 2003, before widespread use of pneumococcal conjugate vaccine in children, which has been associated with a ‘herd immunity’ effect, reducing the incidence of invasive pneumococcal disease in unvaccinated adults.
Figures reported by the European Centre for Disease Prevention and Control (ECDC) in EEA countries indicate a slight decrease in the rate of confirmed and notified cases of invasive pneumococcal disease between 2006 to 2009, from 5.92 per 100 000 to 4.32 per 100 000 (figure 3). It should be noted, however, that there is a wide heterogeneity of the type of surveillance systems in place in different countries, as well as in their coverage and the case definition used, while in some countries there are no surveillance systems at all.
The development of effective pneumococcal vaccines was hampered by the poor immunogenicity of bacterial cell-surface polysaccharides. In the early 1980s, a vaccine containing purified capsular polysaccharides from 23 of the known pneumococcal serotypes (PPV-23) was marketed in the USA, and later in Europe. These 23 serotypes are involved in about 85–90% of invasive pneumococcal disease cases among adults. This polysaccharide vaccine stimulates short-lived B-cell immune responses by causing B-cells to differentiate into plasma cells, producing antibodies without producing memory B-cells. The immunological antibody response is age- and serotype-dependent, and is generally lower in elderly people than in younger adults. There is no memory response to a booster vaccination.
ERS/ESCMID guidelines indicate that the PPV-23 polysaccharide pneumococcal vaccine prevents invasive pneumococcal disease in older people and in other high-risk groups, and should be given to all adults at risk of pneumococcal disease including those over 65 years of age, those resident in institutions and those with dementia, seizure disorders, congestive heart failure, cerebrovascular disease, COPD, history of previous pneumonia, chronic liver disease, diabetes mellitus, functional or anatomical absence of the spleen or chronic cerebrospinal fluid leakage.
To enhance the immunogenicity of pneumococcal vaccines, conjugate vaccines have been developed. Polysaccharide antigens are chemically joined to a highly immunogenic protein carrier (such as tetanus or diphtheria toxoid). This process leads to the induction of both a B- and a T-cell-dependent response and a memory response to a booster dose of the vaccine.
In 2000, a pneumococcal conjugate vaccine containing capsular polysaccharides from seven pneumococcal serotypes (PCV-7), designed for children under 2 years of age, was approved in the USA. As a result of implementation of this vaccine, there was a striking decrease in invasive pneumococcal disease caused by the vaccine serotypes. Since children are the main reservoir of S. pneumoniae (about 60% of children are carriers), a reduction in the carrier rate in this population had beneficial effects on pneumococcal circulation, with a protective herd effect in adults. An additional observed benefit following the introduction of PCV-7 was a reduction in the rates of antimicrobial-resistant S. pneumoniae invasive pneumococcal disease. New conjugate vaccines are now being evaluated for children and adults: a 10-valent (PCV-10) version, which has been licensed in over 30 countries, and a 13-valent (PCV-13) vaccine. The increased serotype coverage of these vaccines, particularly PCV-13, may expand the clinical benefits of conjugate vaccines in adult populations at risk of pneumococcal disease. Vaccination strategies based on the use of more effective vaccines, in particular the PCV-13 vaccine, are expected to have a substantial public health impact on infectious disease and health service costs, reducing the burden of pneumococcal infection. However, there are concerns that, after introduction of the PCV-7 conjugate vaccine, serotypes covered by the vaccine could be replaced by serotypes not covered by it. Consequently, the introduction of the new conjugate vaccines in 2010 (PCV-10 and PCV-13) requires close monitoring.