Serotype 3 Remains the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2012–2014) Despite Continued Reductions in Other 13-Valent Conjugate Vaccine Serotypes

Abstract

Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) as the leading pneumococcal vaccine used in children through the private sector. Although, neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD) were expected due to herd protection. We characterized n = 1163 isolates recovered from IPD in adults in 2012–2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%), 8 (11%), 19A (7%), 22F (7%), 14 (6%), and 7F (5%). The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%), but was smaller than in the previous period (19% in 2009–2011, p = 0.003). The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 (p < 0.001), mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012–2014 (0.7% to 3.5%, p = 0.011) and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17 to 13%, p = 0.174) and erythromycin resistance (from 19 to 13%, p = 0.034). Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates.

Genome Evolution to Penicillin Resistance in Serotype 3 Streptococcus pneumoniae by Capsular Switching

“…Similar effects were reported in the United States (4) and the European Union (5). However, serotype 3, included in PCV13, remains the leading cause of IPD in adults (5)(6)(7).…”

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Severe Invasive Disease Caused by Serotype 3 Streptococcus Pneumoniae in Italian Children

“…The effectiveness and impact of the 13-valent pneumococcal conjugate vaccine (PCV13) against serotype 3 Streptococcus pneumoniae (ser3) has been repeatedly questioned [1][2][3][4][5]. Ser3 pneumococcus has established itself as one of the leading causes of invasive pneumococcal disease (IPD), even in the post-PCV13 introduction period (post-PCV13) [6], and has been associated with complicated and severe infections in children [5,[7][8][9]. This aggressive behavior can be firstly attributed to microbiological features of the pathogen-like thick polysaccharide capsule [10].…”

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV-15) compared to PCV-13 in healthy older adults

“…Of interest, both PCV15 formulations elicited higher OPA GMTs and IgG GMCs than PCV13 to serotype 3, a serotype that is still associated with a significant burden of pneumococcal disease in children and older adults despite high uptake of PCV13 in children in many countries for several years. [42][43][44] Although serotype-specific OPA GMTs or IgG GMCs were observed to be numerically higher for a given study vaccine than the 2 other study vaccines, the clinical significance of such differences are unknown as no serotype-specific correlate of protection against pneumococcal disease has been established in adults. No clear underlying biological or chemical reasons were found and such differences could be due to chance alone given the number of comparisons tested between PCV15-A, PCV15-B and PCV13.…”