Review
Streptococcus pneumoniae – a review of carriage, infection, serotype replacement and vaccination

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Summary

Invasive pneumococcal infection remains a leading global cause of morbidity and mortality in young children. In developed nations, a substantial decrease in the incidence of IPD has been achieved with inclusion of the 7 valent protein conjugated pneumococcal vaccines (7vPCV) into paediatric vaccine schedules. In contrast, the incidence of IPD has changed little in developing nations. This is likely due to poor access to medical care and pneumococcal vaccination, the accompanying HIV and malnutrition burden, and the fact that 7vPCV does not contain the most common serotypes (1,5, 6A) responsible for IPD in many developing nations. The battle against IPD in developed nations is not over, with the rise of non-7vPCV serotypes since routine 7vPCV vaccination. This has necessitated the development and distribution of pneumococcal vaccines containing 3 or 6 additional serotypes. This article provides an overview on pneumococcal carriage and risk factors for IPD, the rise of non-7vCPV serotypes in the era of 7vPCV vaccination, and the current and newly available broader valent pneumococcal vaccines.

Introduction

Streptococcus pneumoniae (pneumococcus) remains one of the leading global causes of childhood pneumonia and meningitis.1 Almost all isolates that cause infection are encapsulated, and to date 91 separate capsular serotypes have been identified. Ten years ago pneumococcal pneumonia caused an estimated 1.8 million deaths worldwide in children < 5 years of age.1 The single most important advance in the fight against pneumococcus has been the development of the penta-valent pneumococcal protein conjugated vaccine (7vPCV; Prevenar 7, Wyeth Pharmaceuticals). 7vPCV is now registered in > 70 countries. The pneumococcal disease spectrum encompasses invasive pneumococcal disease (IPD), defined as the isolation of pneumococcus from normally sterile body fluids (e.g. meningitis, sepsis and bacteraemic pneumonia), as well as non-IPD such as non-bacteraemic pneumonia and otitis media. Surveillance systems of pneumococcal disease vary by country and reduction in IPD incidence is often used as a measure of vaccine success. Since its inclusion into many paediatric vaccination schedules, the incidence of and mortality from IPD in children has fallen2, 3, 4, 5, 6, 7, 8 (Figure 1). A concomitant decrease in adult IPD cases has been attributed in part to herd immunity.6 The efficacy of 7vPCV (i.e. disease reduction) is typically greater for IPD (>80%), compared to radiological or hospital admitted pneumonia (usually < 20%) and otitis media (typically < 10%) (reviewed in4). This is not unexpected, since many other potential pathogens can cause pneumonia and otitis media, and definitions for these two diseases are more problematic. Pressures exerted by antibiotic overuse in inducing multi-resistant strains,9 limited access to vaccination and medical care with accompanying HIV burden in developing nations and the rise of IPD by non-7vPCV serotypes10, 11 has meant pneumococcus remains a significant cause of paediatric infection morbidity, mortality and health care cost.12, 13 This review will discuss carriage and risk factors for IPD, the rise of non-7vPCV serotypes causing infection, and the current and more recent pneumococcal vaccines.

Section snippets

Carriage

Pneumococcus is carried in the nasopharynx, and often with other encapsulated bacteria, such as Haemophilus influenza and Moraxella catarrhalis.14, 15, 16 It is spread by respiratory droplet and children are the main source of transmission to adults. Universally, carriage rates are highest in young children (40–60%), compared with older children (12%), adolescents (6–10%) and adults (3–4%).17, 18 Pneumococcal colonisation is a dynamic process. One serotype is usually carried at a time, with the

Infection

Host and pathogen factors that increase the risk of IPD are summarised (Table 1). Carriage is a pre-requisite for infection and infection usually occurs within a month of acquiring of a new serotype.19 IPD is more likely in individuals that have the highest carriage rates, such as in young children and in indigenous populations.10, 27 Increased predisposition to IPD in infants may be due to a combination of poor natural humoral immunity to the polysaccharide capsule25 and increased

Serotype Replacement

The pattern of predominant IPD associated serotypes varies with age, country, and over time.35 In young children and immune-compromised hosts, typically less immunogenic serotypes (e.g. 6, 14, 19 and 23) predominate. More invasive serotypes (e.g. 1, 5, and 7) tend to infect individuals without co-morbidities.36 Globally, seven serotypes account for the bulk of IPD disease (1, 5, 6A, 6B, 14, 19F and 23F).37, 38 Serotypes 1, 5, 6A/6B, and 14 are the predominant strains causing IPD in most

23vPCV vaccination

The polysaccharide 23vPCV vaccine contains more serotypes than any other available pneumococcal vaccines, and potentially could cover > 85% of serotypes causing IPD in many countries.43 However its use in children < 18 months of age is not recommended, the group most risk of IPD, since such children exhibit poor antibody responses to polysaccharide antigens.25 Balloch et al50 demonstrated 23vPCV is potentially more immunogenic than previously thought, examining responses in infants 12 months of

Summary

IPD in children has significantly decreased in countries that have included 7vPCV into paediatric vaccination schedules. However, unless developing nations are offered prompt, affordable access to pneumococcal vaccines, IPD will remain a major global cause of death in young children. Initiatives such as GAVI and PneumoADIP are currently addressing this imbalance. Pneumococcal vaccination, however, may be a two-edge sword. The initial benefits in disease reduction may be followed by a steady

Conflicts of interest

None to declare

Statement of approval

This is the work of Dr Sam Mehr and Dr Nick Wood.

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