Serotypes 1, 7F and 19A became the leading causes of pediatric invasive pneumococcal infections in Portugal after 7 years of heptavalent conjugate vaccine use
Introduction
The remarkable efficacy of the seven-valent conjugate vaccine (PCV7) against the Streptococcus pneumoniae (pneumococcus) serotypes included in its formulation resulted in a sharp decline in the proportion of invasive infections caused by the serotypes targeted by the vaccine [1], [2], [3], [4]. Since at the time of its introduction, five of the seven serotypes in PCV7 accounted for a large fraction of penicillin non-susceptible isolates, the use of PCV7 has also been implicated in the reduction of the proportion of resistant isolates observed in the last years in the USA [5], [6].
Although a reduction in the number of invasive infections caused by PCV7 serotypes was found in all countries where the vaccine was administered, the large reduction in the overall number of invasive infections documented in the USA and Canada [2], [4] was not replicated in Spain [3], [7]. The effect of PCV7 on antibiotic resistance was also variable. While a decrease in penicillin non-susceptibility was noted in all countries among isolates responsible for pediatric IPD in the post-PCV7 period [1], [3], [6], [7], such a decline was not apparent in adults in Canada, Portugal and Spain [1], [2], [7]. These variations can be due to differences in the impact of PCV7 in colonization since it was shown that in Portugal vaccination with PCV7 was not associated with diminished colonization with antibiotic resistant isolates [8].
In spite of these remarkable initial benefits of PCV7, it was always recognized that the serotypes not included in the vaccine could emerge to replace the decline of the PCV7 serotypes. Such a replacement has indeed been observed, although its magnitude was highly variable – being modest in North America [2], [4] and much more significant in Spain [3], [7]. Although serotype 19A has consistently been identified as a dominant non-vaccine serotype, other emerging non-vaccine serotypes differ among the various geographic locations and also between age groups [1], [2], [4] and even within serotype 19A, different genetic lineages emerge in different geographic locations [9]. Taken together, these data highlight the importance of the characteristics of the local pneumococcal population before PCV7 introduction and of local selective forces in conditioning the outcomes of vaccination.
Recognizing that historically important serotypes were not included in PCV7, some of which increased in importance since PCV7 was introduced, two new conjugate vaccine formulations were developed and have recently become commercially available. A 10-valent formulation (PCV10) including, in addition to the PCV7 serotypes, serotypes 1, 5 and 7F, received approval from the European Medicines Agency (EMA) in March 2009. A 13-valent conjugate vaccine (PCV13), including all PCV10 serotypes plus serotypes 3, 19A and 6A, received EMA approval in December 2009 and from the Food and Drugs Administration in February 2010. The introduction of these vaccines into clinical practice has the potential to once again change the characteristics of IPD, eventually blunting or even reversing the rise of some of the most successful serotypes that have emerged since the introduction of PCV7. However, the potential effects of these novel vaccines will probably also be conditioned by the different characteristics of the pneumococcal population causing IPD in each locale.
In Portugal PCV7 is not included in the National Vaccination Plan but, in spite of the absence of reimbursement, there has been a steady increase in vaccine uptake in the 7 years since it became available [1]. In a previous study, we showed that changes in the serotypes causing invasive infections in children closely followed PCV7 availability [1]. This study aimed at documenting the continued changes on serotype distribution and antimicrobial resistance subsequent to vaccination in different pediatric groups and evaluating the potential impact that the availability of PCV10 and PCV13 may have in pediatric IPD in Portugal.
Section snippets
Bacterial isolates
Since 1999, the Portuguese Surveillance Group for the Study of Respiratory Pathogens has monitored pneumococci causing invasive infections in Portugal. This is a laboratory-based surveillance system, in which 30 microbiology laboratories throughout Portugal are asked to identify all isolates responsible for IPD and to send them to a central laboratory for characterization. A case of invasive disease is defined by an isolate of S. pneumoniae recovered from a normally sterile body site and does
Isolate collection
During the 3 years of the study 353 S. pneumoniae isolates were recovered from normally sterile sites (n = 93 in 2006, n = 145 in 2007 and n = 115 in 2008). The majority of the isolates (n = 289, 81.9%) were recovered from blood, 46 isolates (13.0%) from CSF, 11 isolates (3.1%) from pleural fluid and 7 isolates (1.9%) from other normally sterile sites. In terms of age distribution, 163 (46.1%) were recovered from children <2 years, 99 (28.0%) from children 2–5 years and 91 (25.8%) from patients 6–17
Discussion
We have previously shown that increasing PCV7 vaccination outside the national vaccination plan was associated with a dramatic change of the serotypes of pneumococci causing IPD in Portugal [1]. The data presented here document that these changes have continued and that the higher valency vaccines, that have recently become available, will encounter a substantially different pneumococcal population than the one existing when PCV7 was introduced.
The decline in the relative importance of the
Acknowledgments
Members of the Portuguese Group for the Study of Streptococcal Infections are: Teresa Vaz, Marília Gião, Rui Ferreira (Centro Hospitalar do Barlavento Algarvio), Ana Bruschy Fonseca (Hospital de Cascais), Henrique Oliveira (Centro Hospitalar de Coimbra), Ana Cristina Silva, Hermínia Costa (Centro Hospitalar de Entre Douro e Vouga), Margarida Pinto, Odete Chantre, João Marques, Isabel Peres, Isabel Daniel, Ema Canas, Teresa Ferreira, Cristina Marcelo (Centro Hospitalar de Lisboa Central), Lurdes
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On behalf of the Portuguese Group for the Study of Streptococcal Infections, the Portuguese Study Group of Invasive Pneumococcal Disease of the Pediatric Infectious Disease Society.