Streptococcus pneumoniae (i.e., pneumococcus) was independently isolated in American and French laboratories in the early 1880s.1,2 It was one of the first bacteria to be observed using Gram stain, and advances in microscopic techniques allowed it to become established as a cause of pneumonia, meningitis, and otitis media by the end of the nineteenth century.1 During the 1918 Flu Pandemic, secondary bacterial infections—predominantly pneumococcal, contributed to a high infectious disease-related mortality rate.3
Pneumococcus was one of the earliest pathogens for which attempts were made to develop a vaccine. Clinical trials among mineworkers in South Africa in the 1910s found whole-cell, killed vaccines to have limited and transient efficacy.4 Widespread distribution of vaccines did not begin until after the development of a pneumococcal polysaccharide vaccine (PPSV) targeting 14 serotypes (licensed in 1977) and later 23 serotypes (licensed in 1983).4 In 1981, the U.S. Advisory Committee on Immunization Practices (ACIP) recommended all adults ≥ 65 years to be vaccinated with PPSV14, and this was updated to PPSV23 in 1984.5 Polysaccharide vaccines do not induce a substantial antibody response in infants, however, and they elicit only a short term immunity.6 A more immunogenic pediatric vaccine formulation was licensed in 2000, in the form of the 7-valent pneumococcal conjugate vaccine (PCV), which was expanded to a 13-valent form, licensed in 2010.7,8 PCV is notable for being one of the most expensive vaccines currently available at over $150 per dose, although many studies have shown it cost-effective.9,10 The World Health Organization (WHO) recommended inclusion of PCV in every country’s immunization schedule—the Expanded Program on Immunization, in 2012.11 The widespread introduction of pneumococcal vaccines has led to a rapid decline in pneumococcal pneumonia and invasive pneumococcal disease (i.e., meningitis and bacteremia),12 but there remain theoretical concerns about serotype replacement.
There are 97 known serotypes of pneumococcus, which can be classified according to what is commonly known as the Danish system.13 Pneumococcal serotypes, or strains, are typically differentiated based on the polysaccharide capsule surrounding the bacterium, the role of which is to help the bacteria avoid the immune system and prevent phagocytosis.14,15 However, nonencapsulated strains exist and can also cause disease, particularly in cases of conjunctivitis with 80% of pneumococcal infections involving nonencapsulated strains and in cases of otitis media with 8% nonencapsulated.16 Immunity to pneumococcus is serotype-specific, although related serotypes (termed “serogroups”) may provide some cross protection, particularly for serogroup 6.17 Understanding the serotype distribution within a population has been an important area of research both to identify which serotypes should be targeted by vaccines and to evaluate the cost-effectiveness and success of public immunization programs.
The distribution of pneumococcal serotypes varies by age, geographical location, time, site of infection, and in their propensity to result in asymptomatic colonization versus invasive disease. Seven serotypes (in descending order: ...