Pediatric Pneumococcal Serotypes in 4 European Countries

TOC Summary: Non–heptavalent pneumococcal conjugate vaccine serotypes have increased in Spain, France, Belgium, and England and Wales

Nationwide trends of invasive pneumococcal disease in Spain (2009-2019) in children and adults during the pneumococcal conjugate vaccine era.

Introduction of pneumococcal conjugate vaccines (PCVs) has shown a marked reduction in the disease caused by vaccine serotypes in children providing herd protection to the elderly group. However, the emergence of non-vaccine serotypes is of great concern worldwide. This study includes national laboratory data from invasive pneumococcal disease (IPD) cases affecting pediatric and adult population during 2009-2019. The impact of implementing different vaccine strategies for immunocompetent adults comparing Spanish regions using PCV13 vs regions using PPV23 vaccine was also analyzed for 2017-2019. The overall reductions of IPD cases by PCV13 serotypes in children and adults were 88% and 59% respectively during 2009-2019 with a constant increase of serotype 8 in adults since 2015. IPD cases by additional serotypes covered by PPV23 increased from 20% in 2009 to 52% in 2019. In children, serotype 24F was the most frequent in 2019 whereas in adults, serotypes 3 and 8 accounted for 36% of IPD cases. Introduction of PCV13 or PPV23 in the adult calendar of certain Spanish regions reduced up to 25% and 11% respectively the IPD cases by PCV13 serotypes, showing a decrease of serotype 3 when PCV13 was used. Use of PCV13 in children has shown a clear impact in pneumococcal epidemiology reducing the burden of IPD in children but also in adults by herd protection although the increase of serotype 8 in adults is worrisome. Vaccination with PCV13 in immunocompetent adults seems to control IPD cases by PCV13 serotypes including serotype 3.This work was supported by Ministerio de Economía, Industria y Competitividad (MINECO) [grant SAF2017-83388] and internal funding fromS

Indirect effects of paediatric conjugate vaccines on invasive pneumococcal disease in older adults

Streptococcus pneumoniae; IPD; PCV13; Adults; Case fatality rate; Comorbidities; MortalitySteotococos neumonia; IPD; PCV13; Adultos; Tasa de letalidad; Comorbilidades; MortalidadStreptococcus pneumoniae; IPD; PCV13; Adults; Taxa de letalitat; Comorbiditats; MortalitatObjectives The aim of this study was to assess the indirect effect of paediatric 13-valent pneumococcal conjugate vaccine (PCV13) vaccination on people ≥65 years of age with invasive pneumococcal disease (IPD) in Catalonia and to determine factors predictive of mortality. Methods During 2014–2016, 1285 IPD cases were reported to the Public Health Agency of Catalonia. The indirect effect of paediatric PCV13 vaccination was calculated by comparing the incidence rate (IR) in 2016 (PCV13 year) with that in 2009 (pre-PCV13). Predictors of mortality were determined using multivariate logistic regression. Results Comparing 2016 and 2009, IPD decreased by 19% (IR 40.1 and 32.5 per 100 000 person-years, respectively). PCV13 serotypes decreased by 57% (IR 23.7 and 10.1), while non-PCV13 serotypes increased by 36% (IR 16.4 and 22.4). During 2014–2016, the mortality rate was 17.5%, and mortality was associated with age ≥85 years (adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.89, 4.48), meningitis (aOR 2.29, 95% CI 1.25, 4.19), non-focal bacteraemia (aOR 3.73, 95% CI 2.00, 6.94), and ≥1 high-risk condition (aOR 1.89, 95% CI 1.08, 3.32). PPV23non13 serotypes were associated with lower mortality than PCV13 serotypes (aOR 0.54, 95% CI 0.34, 0.86). Conclusions The incidence of IPD in people ≥65 years of age decreased after the introduction of paediatric PCV13, and this was due to a reduction in PCV13 serotypes, although an increase in non-PCV13 serotypes was observed. Mortality was associated with age, meningitis, non-focal bacteraemia, ≥1 high-risk condition, and PCV13 serotypes

Activity of cefpodoxime and other oral beta-lactams against Haemophilus influenzae and Streptococcus pneumoniae with different susceptibilities to penicillin

[ES] Estudiamos la influencia de la producción de betalactamasas en Haemophilus influenzae y del grado de sensibilidad a la penicilina en Streptococcus pneumoniae sobre la actividad intrínseca de distintos betalactámicos orales. Realizamos tres subestudios: 1) un estudio general de sensibilidad, analizando 550 aislamientos consecutivos recibidos en el Laboratorio de Referencia de Neumococos durante los meses de febrero y marzo de 2005; 2) un estudio de la influencia de la sensibilidad a la penicilina sobre la actividad del resto de los betalactámicos, analizando la sensibilidad de 251 cepas sensibles a la penicilina (CMI ≤0,06 mg/l), 165 cepas con resistencia intermedia (CMI 0,12-1mg/l) y 139 resistentes (CMI ≥2 mg/l), elegidas aleatoriamente entre todos los aislamientos recibidos durante el año 2005; y 3) un estudio desensibilidad de H. influenzae, analizando 150 cepas recibidas por el Instituto Valenciano de Microbiología a lo largo del año 2005. El 71% de las cepas de S. pneumoniae fueron sensibles a la penicilina, el 21% presentaron baja resistencia o resistencia intermedia, y un 8% altaresistencia. La tasa de producción de betalactamasas fue del 18,6% en H. influenzae. El 3% de las cepas no productoras de betalactamasas fueron no sensibles a la ampicilina. La cefpodoxima y la cefixima presentaron la mayor actividad intrínseca frente a H. influenzae, mientras que frente a S. pneumoniae ésta correspondió a la amoxicilina y la cefpodoxima. Mientras que el 100% de las cepas de H. influenzae fueron sensibles a las cefalosporinas orales y a amoxicilina-ácido clavulánico, el aumento de la resistencia a la penicilina en S. pneumoniae afectó en mayor grado a la actividad de la cefixima, el cefaclor y la cefuroxima que a la amoxicilina y la cefpodoxima. [EN] his study explores the influence on the intrinsic activity of different oral beta-lactams of beta-lactamase production in Haemophilus influenzae and penicillin resistance in Streptococcus pneumoniae. Three substudies were performed: a) a general susceptibility study, analyzing 550 strains received by the Spanish Laboratorio de Referencia de Neumococos throughout February and March 2005; b) a study on the influence of penicillin resistance on the activity of beta-lactams, analyzing 251 penicillin-susceptible strains (MICor=2 mg/l) randomly chosen among those received by the Spanish Laboratorio de Referencia de Neumococos throughout 2005; and c) an H. influenzae susceptibility study analyzing 150 strains received by Instituto Valenciano de Microbiologia throughout 2005. A total of 71% of S. pneumoniae strains were susceptible to penicillin, 21% exhibited intermediate resistance and 8% strains presented full resistance. H. influenzae beta-lactamase production rate was 18.6%. Of the non-beta-lactamase-producing strains, 3% were not susceptible to ampicillin. Cefpodoxime and cefixime exhibited the highest intrinsic activity against H. influenzae, while amoxicillin and cefpodoxime were the most active compounds against S. pneumoniae. All H. influenzae strains were susceptible to oral cephalosporins and amoxicillin/clavulanic acid. The increase in penicillin resistance in S. pneumoniae influenced cefixime, cefaclor and cefuroxime to a higher degree than amoxicillin and cefpodoxime.S

Immunization with LytB protein of Streptococcus pneumoniae activates complement-mediated phagocytosis and induces protection against pneumonia and sepsis.

The cell wall glucosaminidase LytB of Streptococcus pneumoniae is a surface exposed protein involved in daughter cell separation, biofilm formation and contributes to different aspects of the pathogenesis process. In this study we have characterized the antibody responses after immunization of mice with LytB in the presence of alhydrogel as an adjuvant. Enzyme-linked immunosorbent assays measuring different subclasses of immunoglobulin G, demonstrated that the antibody responses to LytB were predominantly IgG1 and IgG2b, followed by IgG3 and IgG2a subclasses. Complement-mediated immunity against two different pneumococcal serotypes was investigated using sera from immunized mice. Immunization with LytB increased the recognition of S. pneumoniae by complement components C1q and C3b demonstrating that anti-LytB antibodies trigger activation of the classical pathway. Phagocytosis assays showed that serum containing antibodies to LytB stimulates neutrophil-mediated phagocytosis against S. pneumoniae. Animal models of infection including invasive pneumonia and sepsis were performed with two different clinical isolates. Vaccination with LytB increased bacterial clearance and induced protection demonstrating that LytB might be a good candidate to be considered in a future protein-based vaccine against S. pneumoniae.This work was supported by grants SAF2012-39444-C01/02 from Ministerio de Economía y Competitividad (MINECO). Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) is an initiative of ISCIII. BC and LA were supported, respectively, by a fellowship from the Brazilian Program Ciencia Sem Fronteiras (CsF) from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and by an FPI fellowship from MINECO. The authors wish to thank Sandra Martín for technical assistanceS

Fluoroquinolone-resistant pneumococci: dynamics of serotypes and clones in Spain in 2012 compared with those from 2002 and 2006

In Spain, rates of ciprofloxacin resistance in pneumococci were low during the last decade (2.6% in 2002 and 2.3% in 2006). In 2012, the rate remained at 2.3%, equivalent to 83 of 3,621 isolates. Of the 83 resistant isolates, 15 showed a low level (MIC of 4 to 8 μg/ml) and 68 a high level (MIC of 16 to 128 μg/ml) of ciprofloxacin resistance. Thirteen low-level-resistant isolates had single changes in ParC, one had a single ParE change, and one did not present any mutations. High-level-resistant isolates had GyrA changes plus additional ParC and/or ParE changes: 51, 15, and 2 isolates had 2, 3, or 4 mutations, respectively. Although 24 different serotypes were observed, 6 serotypes accounted for 51.8% of ciprofloxacin-resistant isolates: 8 (14.5%), 19A (10.8%), 11A (7.2%), 23A (7.2%), 15A (6.0%), and 6B (6.0%). A decrease in pneumococcal 7-valent conjugate vaccine (PCV7) serotypes was observed from 2006 (35.7%) to 2012 (16.9%), especially of serotype 14 (from 16.3% to 2.4%; P<0.001). In comparison with findings in 2006, multidrug resistance was greater in 2012 (P=0.296), mainly due to the increased presence and/or emergence of clonal complexes associated with non-PCV7 serotypes: CC63 expressing serotypes 8, 15A, and 19A; CC320 (with serotype 19A); and CC42 (with serotype 23A). Although rates of ciprofloxacin resistance remained low and stable throughout the last decade, changes in serotype and genotype distributions were observed in 2012, notably the expansion of a preexisting multidrug-resistant clone, CC63, and the emergence of the CC156 clone expressing serotype 11A.This study was supported by grant BIO2011-25343 from the Ministerio de Ciencia y Tecnología, by grant PI11/0763 from the Fondo de Investigaciones Sanitarias, and by Ciber de Enfermedades Respiratorias, an initiative of the Instituto de Salud Carlos III. A.D. was supported by an Agustí Pumarola grant from the Societat Catalana de Malaties Infecciones i Microbiologia Clínica and the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

Indirect effects of paediatric conjugate vaccines on invasive pneumococcal disease in older adults

OBJECTIVES: The aim of this study was to assess the indirect effect of paediatric 13-valent pneumococcal conjugate vaccine (PCV13) vaccination on people ≥65 years of age with invasive pneumococcal disease (IPD) in Catalonia and to determine factors predictive of mortality. METHODS: During 2014-2016, 1285 IPD cases were reported to the Public Health Agency of Catalonia. The indirect effect of paediatric PCV13 vaccination was calculated by comparing the incidence rate (IR) in 2016 (PCV13 year) with that in 2009 (pre-PCV13). Predictors of mortality were determined using multivariate logistic regression. RESULTS: Comparing 2016 and 2009, IPD decreased by 19% (IR 40.1 and 32.5 per 100 000 person-years, respectively). PCV13 serotypes decreased by 57% (IR 23.7 and 10.1), while non-PCV13 serotypes increased by 36% (IR 16.4 and 22.4). During 2014-2016, the mortality rate was 17.5%, and mortality was associated with age ≥85 years (adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.89, 4.48), meningitis (aOR 2.29, 95% CI 1.25, 4.19), non-focal bacteraemia (aOR 3.73, 95% CI 2.00, 6.94), and ≥1 high-risk condition (aOR 1.89, 95% CI 1.08, 3.32). PPV23non13 serotypes were associated with lower mortality than PCV13 serotypes (aOR 0.54, 95% CI 0.34, 0.86). CONCLUSIONS: The incidence of IPD in people ≥65 years of age decreased after the introduction of paediatric PCV13, and this was due to a reduction in PCV13 serotypes, although an increase in non-PCV13 serotypes was observed. Mortality was associated with age, meningitis, non-focal bacteraemia, ≥1 high-risk condition, and PCV13 serotypes.This study was partially supported by SpIDnet (Assessing the impact of vaccination with conjugate vaccines on the epidemiology of invasive pneumococcal disease in Europe), a network funded by the European Centre for Disease Prevention and Control ( ECDC/2015/031 ); the Catalan Agency for the Management of Grants for University Research ( AGAUR Grant number 2017/SGR 1342 and 2017/SGR 0742 ); the Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública ( CIBERESP CB06/02/0076 and CB15/00067 ); and the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias ( CIBERES CB06/06/0037 ).S