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Background: In April 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunisation schedule in England and Wales. Despite limited serotype replacement in invasive pneumococcal disease (IPD) during the first four post-PCV13 years, non-vaccine type (NVT) IPD increased substantially in 2014/15. We undertook a carriage study in 2015/16 to help understand the reasons for this increase. Methods and findings: Families with a child aged <5 years attending a participating general practice in Gloucestershire or Hertfordshire were invited to provide nasopharyngeal swabs from all consenting members. Swabs from 650 individuals (293 under five, 73 five to twenty and 284 >twenty years) were cultured and serotyped for Streptococcus pneumoniae. Results were compared with those from three previous household studies conducted in the same populations between 2001 to 2013, and with the serotypes causing IPD to estimate case-carrier ratios (CCRs). Overall carriage prevalence did not differ between the four carriage studies with reductions in vaccine-type carriage offset by increases in NVT carriage. While no individual NVT serotype showed an increase in CCR from 2012/13, the composition of the serotypes comprising the NVT group differed such that the overall CCR of the NVT group had significantly increased since 2012/13. Carriage of two PCV13 serotypes, 3 and 19A, was found in 2015/16 (3/650 = 0.5% and 2/650 = 0.3% respectively) with no overall reduction in carriage prevalence of PCV13-7 serotypes since 2012/13, though 6C prevalence, a vaccine-related serotype, had reduced from 1.8% in 2012/13 to 2/648 (0.3%) in 2015/16, p = 0.013. Conclusions: There was continuing evolution in carried NVTs six years after PCV13 introduction which, in addition to being vaccine-driven, could also reflect natural secular changes in certain NVTs. This poses challenges in predicting future trends in IPD. Elimination of carriage and disease due to serotypes 3 and 19A may not be achieved by PCV13. [ABSTRACT FROM AUTHOR]

Background. This study aimed to estimate, following invasive pneumococcal disease (IPD), the proportion of children with protective immunoglobulin G (IgG) concentrations against the infecting serotype compared with other vaccine serotypes, and to assess risk of recurrent IPD. Methods. Pneumococcal antibody concentrations were available for 413 children with vaccine-type IPD diagnosed during 2006-2013. We compared serotype-specific IgG concentrations against the infecting vs other vaccine serotypes, after adjusting for confounders such as age using multilevel analyses. Results. After IPD, a higher proportion of vaccine-naive children had IgG concentrations ≥0.35 μg/mL against their infecting serotype than other vaccine serotypes (51% vs 36%; P < .001). In contrast, among children immunized with pneumococcal conjugate vaccine (PCV) both before and after IPD, the proportion with IgG concentrations ≥0.35 μg/mL against the infecting serotype was lower compared with other vaccine serotypes (71% vs 98%; P < .001). These children also had lower IgG geometric mean concentrations (GMCs) against the infecting serotype (2.22 μg/mL) vs other vaccine serotypes (15.64 μg/mL) in multilevel models (IgG GMC ratio, 0.24; 95% confidence interval, .18-.32), although their IgG GMC was higher compared with vaccine-naive children. Vaccinated children with IgG concentrations <0.35 μg/mL against their infecting serotype generally remained unresponsive despite further vaccine doses. However, recurrent IPD with the same infecting serotype was rare (7/3030 children [0.2%]) and not associated with unresponsiveness. Conclusions. Vaccination with PCV before and/or after IPD was associated with lower IgG concentrations against the infecting serotype compared with other vaccine serotypes, but recurrent IPD was rare. Further studies are needed to understand this phenomenon in immunized children. [ABSTRACT FROM AUTHOR]

The article discusses the explanation of the results of the study by researcher L. Olarte and colleagues about the impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis (PM) in U.S. children. It mentions the explanation by varying invasive pneumococcal disease (IPD) profiles according to serotypes. It adds reduction in IPD cases with PCVs.

Introduction: In England, antenatal pertussis immunization using a tetanus/low-dose diphtheria/5-component acellular-pertussis/inactivated-polio (TdaP5/IPV) vaccine was introduced in October 2012.We assessed infant responses to antigens in the maternal vaccine and to those conjugated to tetanus (TT) or the diphtheria toxin variant, CRM. Methods: Infants of 141 TdaP5/IPV-vaccinated mothers in Southern England immunized with DTaP5/IPV/ Haemophilus influenzae b (Hib-TT) vaccine at 2-3-4 months, 13-valent pneumococcal vaccine (PCV13, CRMconjugated) at 2-4 months and 1 or 2 meningococcal C vaccine (MCC-CRM- or MCC-TT) doses at 3-4 months had blood samples taken at 2 and/or 5 months of age. Results: Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae 2 + 3 (FIMs), diphtheria, tetanus, Hib,MCC and PCV13 serotypes were compared to responses in a historical cohort of 246 infants born to mothers not vaccinated in pregnancy. Infants had high pertussis antibody concentrations pre-immunization but only PT antibodies increased post-immunization (fold-change, 2.64; 95% confidence interval [CI], 2.12-3.30; P < .001), whereas FHA antibodies fell (fold-change, 0.56; 95% CI, .48-.65; P < .001). Compared with infants of unvaccinated mothers, PT, FHA, and FIMs antibodies were lower post-vaccination, with fold-differences of 0.67 (0.58-0.77; P < .001), 0.62 (0.54- 0.71; P < .001) and 0.51 (0.42-0.62; P < .001), respectively. Antibodies to diphtheria and some CRM-conjugated antigens were also lower, although most infants achieved protective thresholds; antibodies to tetanus and Hib were higher. Conclusions: Antenatal pertussis immunization results in high infant pre-immunization antibody concentrations, but blunts subsequent responses to pertussis vaccine and some CRM-conjugated antigens. In countries with no pertussis booster until school age, continued monitoring of protection against pertussis is essential. [ABSTRACT FROM AUTHOR]

Background: This study aimed to estimate, following invasive pneumococcal disease (IPD), the proportion of children with protective immunoglobulin G (IgG) concentrations against the infecting serotype compared with other vaccine serotypes, and to assess risk of recurrent IPD. Methods: Pneumococcal antibody concentrations were available for 413 children with vaccine-type IPD diagnosed during 2006-2013. We compared serotype-specific IgG concentrations against the infecting vs other vaccine serotypes, after adjusting for confounders such as age using multilevel analyses. Results: After IPD, a higher proportion of vaccine-naive children had IgG concentrations ≥0.35 μg/mL against their infecting serotype than other vaccine serotypes (51% vs 36%; P < .001). In contrast, among children immunized with pneumococcal conjugate vaccine (PCV) both before and after IPD, the proportion with IgG concentrations ≥0.35 μg/mL against the infecting serotype was lower compared with other vaccine serotypes (71% vs 98%; P < .001). These children also had lower IgG geometric mean concentrations (GMCs) against the infecting serotype (2.22 μg/mL) vs other vaccine serotypes (15.64 μg/mL) in multilevel models (IgG GMC ratio, 0.24; 95% confidence interval, .18-.32), although their IgG GMC was higher compared with vaccine-naive children. Vaccinated children with IgG concentrations <0.35 μg/mL against their infecting serotype generally remained unresponsive despite further vaccine doses. However, recurrent IPD with the same infecting serotype was rare (7/3030 children [0.2%]) and not associated with unresponsiveness. Conclusions: Vaccination with PCV before and/or after IPD was associated with lower IgG concentrations against the infecting serotype compared with other vaccine serotypes, but recurrent IPD was rare. Further studies are needed to understand this phenomenon in immunized children. [ABSTRACT FROM AUTHOR]

Summary Background The 13-valent pneumococcal conjugate vaccine (PCV13) protects against key serotypes that increased after routine immunisation with the seven-valent vaccine (PCV7), but its potential for herd protection and serotype replacement is uncertain. The aim of this study was to analyse the effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction. Methods We used a national dataset of electronically reported and serotyped invasive pneumococcal disease cases in England and Wales to estimate incidence rate ratios (IRRs) for vaccine and non-vaccine type invasive pneumococcal disease between July, 2013, and June, 2014, versus the pre-PCV13 and pre-PCV7 baseline. Incidence rates were corrected for missing serotype data and changes in surveillance sensitivity over time. An over-dispersed Poisson model was used to estimate IRRs and confidence intervals. Findings Incidence of invasive pneumococcal disease in the epidemiological year 2013/14 decreased by 32% compared with the pre-PCV13 baseline (incidence 10·14 per 100 000 in 2008–10 vs 6·85 per 100 000 in 2013/14; IRR 0·68, 95% CI 0·64–0·72). This was due to an 86% reduction of the serotypes covered by PCV7 (1·46 vs 0·20 per 100 000; IRR 0·14, 0·10–0·18) and a 69% reduction of the additional six serotypes covered by PCV13 (4·48 vs 1·40 per 100 000; IRR 0·31, 0·28–0·35). When compared with the pre-PCV7 baseline, there was a 56% overall reduction in invasive pneumococcal disease (15·63 vs 6·85 per 100 000; IRR 0·44, 95% CI 0·43–0·47). Compared with the pre-PCV13 baseline, the incidence of non-PCV13 serotypes increased (incidence all ages 4·19 vs 5·25 per 100 000; IRR 1·25, 95% CI 1·17–1·35) due to increases across a broad range of serotypes in children younger than 5 years and in people aged 45 years or more. In children younger than 5 years, incidence of non-PCV13 serotypes in 2013/14 was higher than in 2012/13 (age <2 years: 12·03 vs 10·83 per 100 000; age 2–4 years: 4·08 vs 3·63 per 100 000). Interpretation 8 years of PCV use in England and Wales has reduced the overall incidence of invasive pneumococcal disease by more than 50%. The herd protection induced by PCV7 is continuing, and similar indirect protection is occurring from the additional serotypes covered by PCV13. There is, however, evidence of increasing invasive pneumococcal disease due to non-PCV13 serotypes, particularly in children younger than 5 years in 2014. If this increase continues, the maximum benefit of the PCV13 programme in children might already have been achieved. Funding Public Health England funds national surveillance of invasive pneumococcal disease. [ABSTRACT FROM AUTHOR]

Summary Background Efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) was inferred before licensure from an aggregate correlate of protection established for the seven-valent vaccine (PCV7). We did a postlicensure assessment of serotype-specific vaccine effectiveness and immunogenicity in England, Wales, and Northern Ireland to derive the correlates of protection for individual serotypes. Methods We assessed vaccine effectiveness against invasive pneumococcal disease using the indirect cohort method. We measured serotype-specific IgG concentration in infants after they were given two priming doses of PCV7 (n=126) or PCV13 (n=237) and opsonophagocytic antibody titre from a subset of these infants (n=100). We derived correlates of protection by relating percentage protection to a threshold antibody concentration achieved by an equivalent percentage of infants. We used multivariable logistic regression to estimate vaccine effectiveness and reverse cumulative distribution curves to estimate correlates of protection. Findings For the 706 cases of invasive pneumococcal disease included in the study, PCV13 vaccine effectiveness after two doses before age 12 months or one dose from 12 months was 75% (95% CI 58–84). Vaccine effectiveness was 90% (34–98) for the PCV7 serotypes and 73% (55–84) for the six additional serotypes included in PCV13. Protection was shown for four of the six additional PCV13 serotypes (vaccine effectiveness for serotype 3 was not significant and no cases of serotype 5 infection occurred during the observation period). The vaccine effectiveness for PCV13 and PCV7 was lower than predicted by the aggregate correlate of protection of 0·35 μg/mL used during licensing. Calculated serotype-specific correlates of protection were higher than 0·35 μg/mL for serotypes 1, 3, 7F, 19A, 19F, and lower than 0·35 μg/mL for serotypes 6A, 6B, 18C, and 23F. Opsonophagocytic antibody titres of 1 in 8 or higher did not predict protection. Interpretation PCV13 provides significant protection for most of the vaccine serotypes. Although use of the aggregate correlate of protection of 0·35 μg/mL has enabled the licensing of effective new PCVs, serotype-specific correlates of protection vary widely. The relation between IgG concentration after priming and long-term protection needs to be better understood. Funding Public Health England and UK Department of Health Research and Development Directorate. [ABSTRACT FROM AUTHOR]

Abstract: In 2003 the existing 23-valent pneumococcal vaccine (PPV23) programme for high risk groups was extended to include all ≥65 year olds in England and Wales, starting with ≥80 year olds and moving to 75–79 and 65–74 year olds by 2005. We conducted an ecological study to assess the impact of the extended PPV23 programme on serotype-specific incidence of invasive pneumococcal disease (IPD) and a case–control study to assess vaccine effectiveness (VE) using the national IPD surveillance dataset. Between 1998 and 2006 IPD incidence caused by PPV23 serotypes in the targeted age-groups was unchanged. IPD caused by the serotypes covered by the 7-valent conjugate vaccine (PCV7) introduced for children in 2006 declined in ≥65 year olds after 2006 but was offset by an increase in non-PCV7 serotypes. This increase was similar for the additional 16 serotypes covered by PPV23 and the non-PPV23 serotypes. For the VE study, vaccine history was obtained for controls (n =1270) with non-PPV23 IPD diagnosed between November 2003 and December 2010 and a subset of cases (n =1272) matched for age and time period. VE declined from 48% (95% confidence interval; 32–60%) within two years of vaccination to 15% (−3% to 30%) after five years. Although differences in VE by age and having risk conditions were not statistically significant the highest estimates were in the youngest age group (65–74 years) and in those without risk conditions with a VE estimate of 65% (23–84%) within 2 years of vaccination for non-risk 65–74 year olds. VE differed by serotype (p =0.005), from −23% (−85% to 19%) for serotype 3 to 63% (29–81%) for 12F. In conclusion PPV23 was effective, particularly in healthy under 75 year olds, but protection waned after 5 years. There was no discernible impact of PPV23 on IPD incidence or PCV7-induced serotype replacement, consistent with the modest overall effectiveness, the 45% increased coverage over the former risk-based programme and lack of herd immunity from the PPV23 programme. Based on the VE estimates PPV23 was still considered a cost-effective intervention for the low risk elderly. [Copyright &y& Elsevier]

Visual search is markedly improved when a target color change is synchronized with a spatially non-informative auditory signal. This "pip and pop" effect is an automatic process as even a distractor captures attention when accompanied by a tone. Previous studies investigating visual attention have indicated that automatic capture is susceptible to the size of the attentional window. The present study investigated whether the pip and pop effect is modulated by the extent to which participants divide their attention across the visual field We show that participants were better in detecting a synchronized audiovisual event when they divided their attention across the visual field relative to a condition in which they focused their attention. We argue that audiovisual capture is reduced under focused conditions relative to distributed settings. [ABSTRACT FROM AUTHOR]

Background: The 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2,3 and 13month schedule, and has led to large decreases in invasive pneumococcal disease (IPD) caused by the vaccine serotypes in both vaccinated and unvaccinated cohorts. We estimated the effectiveness of PCV-7 against IPD. Methods and Findings: We used enhanced surveillance data, collated at the Health Protection Agency, on vaccine type (n = 153) and non vaccine type (n = 919) IPD cases eligible for PCV-7. The indirect cohort method, a case-control type design which uses non vaccine type cases as controls, was used to estimate effectiveness of various numbers of doses as well as for each vaccine serotype. Possible bias with this design, caused by differential serotype replacement in vaccinated and unvaccinated individuals, was estimated after deriving formulae to quantify the bias. The results showed good effectiveness, increasing from 56% (95% confidence interval (CI): -7-82) for a single dose given under one year of age to 93% (95% CI: 70-98) for two doses under one year of age plus a booster dose in the second year of life. Serotype specific estimates indicated higher effectiveness against serotypes 4, 14 and 18C and lower effectiveness against 6B. Under the assumption of complete serotype replacement by non vaccine serotypes in carriage, we estimated that effectiveness estimates may be overestimated by about 2 to 5%. Conclusions: This study shows high effectiveness of PCV-7 under the reduced schedule used in the UK. This finding agrees with the large reductions seen in vaccine type IPD in recent years in England and Wales. The formulae derived to assess the bias of the indirect cohort method for PCV-7 can also be used when using the design for other vaccines that affect carriage such as the recently introduced 13 valent pneumococcal conjugate vaccine. [ABSTRACT FROM AUTHOR]

Objective: To describe the epidemiology of invasive pneumococcal disease (IPD) in England & Wales in the pre-conjugate vaccine era.Methods: We analysed reports of culture-confirmed IPD submitted to the national surveillance system between July 1996 and June 2006.Results: The incidence of IPD was 10 per 100,000 overall, and increased over time. The typical pattern of IPD by age was observed, with the highest incidence in young children and older adults. There was little change in IPD incidence in the elderly, despite the widespread use of 23-valent pneumococcal polysaccharide vaccines since 2003. The distribution of serotypes changed over time; notably the proportion of cases caused by serotype 14 decreased, and the proportion due to serotype 1 increased. The incidence of meningitis was 0.6 per 100,000 overall, and as a proportion of all IPD cases was most common in children under 1 year of age (30%). Particular serotypes were significantly associated with a presentation of meningitis, after controlling for age and year, and the case:carrier ratio varied markedly by serotype.Conclusions: This paper provides a baseline for evaluating the impact of 7-valent pneumococcal conjugate vaccines, introduced in September 2006. Ongoing high-quality laboratory-based surveillance of IPD in all age groups is essential. [ABSTRACT FROM AUTHOR]

Abstract: Efficacy of the new serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease (IPD) was based on a putative correlate of protection. In England and Wales, PCV13 replaced PCV7 in the 2, 4, and 13 month schedule in April 2010. Using non-vaccine type IPD cases as controls, we estimated vaccine effectiveness (VE) for the new serotypes. Among 166 IPD cases in PCV13 eligible children reported by July 2011 with known serotype and vaccination status, VE for 2 doses under a year was 78% (95% confidence interval −18% to 96%) and 77% (38–91%) for one dose over a year. VE for 7F and 19A was 76% (21–93%) and 70% (10–90%) respectively for ≥one dose. VE for serotypes 1 and 3 was 62% and 66% respectively although confidence intervals spanned zero. IPD due to PCV13-only serotypes halved in children under 2 years in the study period. [Copyright &y& Elsevier]

Summary: Background: The seven-valent pneumococcal conjugate vaccine (PCV7) has reduced vaccine-type (VT) invasive pneumococcal disease but increases in non-vaccine-type (NVT) disease have varied between countries. We assess the effect of the PCV7 vaccination on VT and NVT disease in England and Wales. Methods: The study cohort was the population of England and Wales from July, 2000, to June, 2010. We calculated incidence rate ratios (IRRs) to compare incidences of VT and NVT disease before (2000–06) and after (2009–10) the introduction of PCV7. We used data from the national surveillance database. Cases included in our analysis were restricted to those confirmed by culture linked with isolates referred for serotyping at the national reference centre by laboratories in England and Wales. We adjusted for potential bias from missing data (serotype and age of patient) and changes in case ascertainment rates during the study period. Findings: 5809 cases of invasive pneumococcal disease were reported in 2009–10, giving an incidence of 10·6 per 100 000 population in 2009–10, which, when compared with the adjusted average annual incidence of 16·1 in 2000–06, gives an overall reduction of 34% (95% CI 28–39). VT disease decreased in all age groups, with reductions of 98% in individuals younger than 2 years and 81% in those aged 65 years or older. NVT disease increased by 68% in individuals younger than 2 years and 48% in those aged 65 years or older, giving an overall reduction in invasive pneumococcal disease of 56% in those younger than 2 years and 19% in those aged 65 years or older. After vaccine introduction, more NVT serotypes increased in frequency than decreased, which is consistent with vaccine-induced replacement. Key serotypes showing replacement were 7F, 19A, and 22F. Increases in NVT invasive pneumococcal disease were not associated with antimicrobial resistance. Interpretation: Despite much serotype replacement, a substantial reduction in invasive pneumococcal disease in young children can be achieved with PCV7 vaccination, with some indirect benefit in older age groups. Further reductions should be achievable by use of higher valency vaccines. Robust surveillance data are needed to properly assess the epidemiological effect of multivalent pneumococcal disease vaccines. Funding: Health Protection Agency. [Copyright &y& Elsevier]