Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: A systematic review and meta-analysis

Abstract

BackgroundRoutine immunisation with pneumococcal conjugate vaccines (PCV7/10/13) has reduced invasive pneumococcal disease (IPD) due to vaccine serotypes significantly. However, an increase in disease due to non-vaccine types, or serotype replacement, has been observed. Serotypes’ individual contributions to IPD play a critical role in determining the overall effects of PCVs. This study examines the distribution of pneumococcal serotypes in children to identify leading serotypes associated with IPD post-PCV introduction.MethodsA systematic search was performed to identify studies and surveillance reports (published between 2000 and December 2015) of pneumococcal serotypes causing childhood IPD post-PCV introduction. Serotype data were differentiated based on the PCV administered during the study period: PCV7 or higher valent PCVs (PCV10 or PCV13). Meta-analysis was conducted to estimate the proportional contributions of the most frequent serotypes in childhood IPD in each period.ResultsWe identified 68 studies reporting serotype data among IPD cases in children. We analysed data from 38 studies (14 countries) where PCV7 was administered and 20 (24 countries) where PCV10 or PCV13 have been introduced. Studies reported early and late periods of PCV7 administration (range: 2001∓13). In these settings, serotype 19A was the most predominant cause of childhood IPD, accounting for 21.8% (95%CI 18.6∓25.6) of cases. In countries that have introduced higher valent PCVs, study periods were largely representative of the transition and early years of PCV10 or PCV13. In these studies, the overall serotype-specific contribution of 19A was lower (14.2% 95%CI 11.1∓18.3). Overall, non-PCV13 serotypes contributed to 42.2% (95%CI 36.1∓49.5%) of childhood IPD cases. However, regional differences were noted (57.8% in North America, 71.9% in Europe, 45.9% in Western Pacific, 28.5% in Latin America, 42.7% in one African country, and 9.2% in one Eastern Mediterranean country). Predominant non-PCV13 serotypes overall were 22F, 12F, 33F, 24F, 15C, 15B, 23B, 10A, and 38 (descending order), but their rank order varied by region.ConclusionChildhood IPD is associated with a wide number of serotypes. In the early years after introduction of higher valent PCVs, non-PCV13 types caused a considerable proportion of childhood IPD. Serotype data, particularly from resource-limited countries with high burden of IPD, are needed to assess the importance of serotypes in different settings. The geographic diversity of pneumococcal serotypes highlights the importance of continued surveillance to guide vaccine design and recommendations.

Response to: Pneumococcal conjugate vaccines in Latin America: are PCV10 and PCV13 similar in terms of protection against serotype 19A?

“…However, this observation is of relative importance in the context of overall incidence of IPD given that the majority of IPD in this vulnerable age-group is caused by non-vaccine types. As described, despite the vaccine introduction, serotype 19A remains a common serotype in older children and adults in most settings, irrespective of the vaccine used, schedule or geographical area [2,14]. We therefore agree with Avila-Aguero et al [1] that further surveillance of IPD is warranted with special attention to 19A.…”

Public health impact of pneumococcal conjugate vaccine infant immunization programs: assessment of invasive pneumococcal disease burden and serotype distribution

“…Serotype 3 contributed to 1-13% of overall IPD in children <5 years old and 6-18% in adults ≥65 years old. In line with these observations, a recent systematic review and meta-analysis of post-PCV serotype distribution showed that serotypes 19A and 3 accounted for 14.2% (95% CI: 11.1-18.3%) and 5.3% (95% CI: 4.2-6.7%), respectively, of childhood IPD cases globally [80]. Strong regional variations were seen in these proportions.…”

“…Similarly, another recent systematic review and meta-analysis that assessed serotype distribution in childhood IPD in the post-PCV era showed that in countries that had introduced higher valent PCVs, NVTs contributed to 42.2% (95% confidence interval [CI]: 36.1-49.5%) of childhood IPD [80]. However, large regional differences were observed; in European countries, the posthigher-valent PCV proportion of NVT IPD was 71.9% (95% CI: 63.1-82.0%) compared to 57.8% (95% CI: 41.6-80.4%) in North America and 28.5% (95% CI: 23.4-34.7%) in Latin America [80]. Most of the data from Latin American countries included in this meta-analysis represented the transition year or first years after higher valent PCV introduction in contrast to the European datasets which also represented later years.…”

“…An important difference is that the authors of this review considered serotype 3 as a NVT [79]. Similarly, another recent systematic review and meta-analysis that assessed serotype distribution in childhood IPD in the post-PCV era showed that in countries that had introduced higher valent PCVs, NVTs contributed to 42.2% (95% confidence interval [CI]: 36.1-49.5%) of childhood IPD [80]. However, large regional differences were observed; in European countries, the posthigher-valent PCV proportion of NVT IPD was 71.9% (95% CI: 63.1-82.0%) compared to 57.8% (95% CI: 41.6-80.4%) in North America and 28.5% (95% CI: 23.4-34.7%) in Latin America [80].…”

Estimating the impact of pneumococcal conjugate vaccines on childhood pneumonia in sub-Saharan Africa: A systematic review

“…There are 97 serotypes of S. pneumoniae currently known based on their polysaccharide capsule antigen(16). The 97 serotypes differ in carriage potential and propensity to cause invasive disease including pneumonia, otitis media and meningitis (17,18), with the thirteen most common serotypes accounting for 70 – 75% of invasive pneumococcal disease globally(8,18,19).…”