Increase in the Prevalence of the Newly Discovered Pneumococcal Serotype 6C in the Nasopharynx after Introduction of Pneumococcal Conjugate Vaccine

Streptococcus pneumoniae is a significant human pathogen responsible for several invasive pneumococcal disease (IPD) syndromes, such as sepsis, meningitis, and pneumonia, as well as more common infections, such as otitis media. Pneumococci are present in the nasopharynges of many healthy children without causing any clinical symptoms [1, 2]. Because pneumococci are only rarely found in animals [3], the human nasopharynx is their dominant natural reservoir and is thus the source of pneumococci in children as well as adults. Consequently, the nasopharyngeal (NP) carriage of pneumococci in humans is central to their transmission. To reduce the burden of pneumococcal infections in children, a 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for clinical use in the United States in February 2000 [4]. PCV7 has significantly reduced the incidence of IPDs in young children as well as in older adults [5, 6]. It has also significantly reduced the frequency of pneumococcal carriage of vaccine serotypes (i.e., the serotypes included in the vaccine) in young children [1, 7]. This reduction in carriage of vaccine serotypes is thought to be responsible for the indirect protection of older adults through herd immunity [8, 9]. Because the conjugate vaccine provides serotype-specific protection, the reduction in IPD, the decrease in carriage, and herd immunity were restricted to vaccine serotypes as well as to some serotypes that are cross-reactive with the vaccine serotypes. However, the prevalence of NP carriage of many nonvaccine serotypes has increased after the introduction of PCV7 [1, 9, 10]. A new pneumococcal serotype, 6C, has recently been identified using monoclonal antibodies [11, 12]. The repeating unit of the 6C polysaccharide (PS) is → 2) glucose (1 → 3) glucose (1 → 3) rhamnose (1 → 3) ribitol (5 → phosphate [12]. In contrast, the 6A PS repeating unit is → 2) galactose (1 → 3) glucose (1 → 3) rhamnose (1 → 3) ribitol (5 → phosphate, and the 6B PS repeating unit is → 2) galactose (1 → 3) glucose (1 → 3) rhamnose (1 → 4) ribitol (5 → phosphate. Genetic studies have found that the galactosyl transferase gene at the capsule gene locus of the 6A serotype is replaced with a glucosyl transferase gene in the 6C serotype [13]. Serologically, serotype 6C is very similar to serotype 6A but is distinct from serotype 6B. Consequently, the 6C serotype has previously been identified by the quellung reaction as the 6A serotype [11]. Postmarketing studies of IPD in children have identified a decline in invasive disease due to serotype 6A [6, 9], suggesting that PCV7, which contains 6B PS, may provide cross-protection against 6A. However, no epidemiologic reports have specifically investigated changes in the prevalence of NP carriage of serotype 6C. If vaccination with PCV7 fails to elicit functional antibody against serotype 6C, it may selectively increase the prevalence of 6C, which was relatively uncommon before the introduction of PCV7 [11, 13]. To investigate this possibility, we examined the prevalence of NP carriage of 6C among 7 cohorts of children in Massachusetts over a 13-year period.