Vaccine 28 (2010) 5167–5173 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Serotypes 1, 7F and 19A became the leading causes of pediatric invasive pneumococcal infections in Portugal after 7 years of heptavalent conjugate vaccine use Sandra I. Aguiar a,1 , Maria J. Brito b,1 , José Gonc ¸ alo-Marques c,1 , José Melo-Cristino a,c,1 , Mário Ramirez a,∗,1 a Instituto de Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, PT 1649-028 Lisboa, Portugal b Centro Hospitalar de Lisboa Central, Lisboa, Portugal c Centro Hospitalar Lisboa Norte, Lisboa, Portugal article info Article history: Received 21 April 2010 Received in revised form 28 May 2010 Accepted 1 June 2010 Available online 15 June 2010 Keywords: Streptococcus pneumoniae Conjugate vaccines Antimicrobial resistance abstract We characterized 353 isolates responsible for pediatric invasive pneumococcal infections (IPD) in Portu- gal between 2006 and 2008. Serotypes included in the seven-valent conjugate vaccine (PCV7) accounted for 17% of IPD. Serotypes 1, 7F and 19A were the most frequent causes of IPD and the later consolidated as the most frequent serotype among erythromycin and penicillin non-susceptible isolates. Serotype 1 was associated with older children and empyemas, while serotype 19A was associated with IPD in younger (<2 years) children. The higher valency vaccines PCV10 and PCV13 have a potentially superior cover- age, 55% and 83% respectively, but non-vaccine serotypes are emerging as important causes of IPD. A decline of resistance with patient age was noted. Comparing with previous data from Portugal, this study showed a continued decline of PCV7 serotypes and that overall resistance has stabilized following the initial decline of the first post-PCV7 years. © 2010 Elsevier Ltd. All rights reserved. 1. Introduction The remarkable efficacy of the seven-valent conjugate vac- cine (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 tar- geted by the vaccine [1–4]. 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 num- ber 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- ∗ Corresponding author. Tel.: +351 21 799 9460; fax: +351 21 799 9459. E-mail addresses: ramirez@fm.ul.pt, ramirma@gmail.com (M. Ramirez). 1 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. 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 pop- ulation 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 0264-410X/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2010.06.008