Search

Introduction: The burden of pneumococcal disease in older UK adults remains substantial. Higher valency pneumococcal conjugate vaccines (PCVs) are currently in development with adult formulations for two of these anticipated to become available in 2022. This article collates and reviews relevant candidate data now available that may be used to support cost effectiveness assessments of vaccinating immunocompetent UK adults aged ≥65-years with PCVs., Areas Covered: This article uses published data from surveillance systems, randomized controlled trials and observational studies. It focuses on local data from the UK but where these are either limited or not available relevant global data are considered., Expert Opinion: The body of relevant data now available suggests the UK is well placed to assess the cost effectiveness of vaccinating immunocompetent ≥65-year olds with new generation higher valency PCVs. Recent contemporary data provide important new and robust insights into the epidemiology of pneumococcal disease in older UK adults and help to address much of the uncertainty and data gaps associated with previous analyses. Using these data to make informed decisions about use of new higher valency PCVs for routine use in older adults will be important for public health in the UK.

Background: In 2016, the travel subcommittee of the UK Joint Committee on Vaccination and Immunisation (JCVI) recommended that 13-valent PCV (PCV13) could be offered to travellers aged over 65 years, visiting countries without infant PCV immunization programmes. This study aimed to identify, collate and review the available evidence to identify specific countries where UK travellers might be at an increased risk of developing pneumococcal infection. The data were then used to develop an algorithm, which could be used to facilitate implementation of the JCVI recommendation., Methods: We conducted a systematic search of the published data available for pneumococcal disease, PCV vaccine implementation, coverage data and programme duration by country. The primary data sources used were World Health Organization databases and the International Vaccine Access Centre Vaccine Information and Epidemiology Window-hub database. Based on the algorithm, the countries were classified into 'high overall risk', 'intermediate overall risk' and 'low overall risk' from an adult traveller perspective. This could determine whether PCV13 should be recommended for UK adult travellers., Results: A data search for a total of 228 countries was performed, with risk scores calculated for 188 countries. Overall, 45 countries were classified as 'high overall risk', 86 countries as 'intermediate overall risk', 57 countries as 'low overall risk' and 40 countries as 'unknown'., Conclusion: To our knowledge this is the first attempt to categorize the risk to UK adult travellers of contracting pneumococcal infection in each country, globally. These findings could be used by national travel advisory bodies and providers of travel vaccines to identify travellers at increased risk of pneumococcal infection, who could be offered PCV immunization., (© International Society of Travel Medicine 2021. Published by Oxford University Press.)

The 13-valent pneumococcal conjugate vaccine (PCV) has been part of routine immunisation in a 2 + 1 schedule (two primary infant doses and one booster during the second year of life) in the UK since 2010. Recently, the UK's Joint Committee on Vaccination and Immunisation recommended changing to a 1 + 1 schedule while conceding that this will increase disease burden; however, uncertainty remains on how much pneumococcal burden - including invasive pneumococcal disease (IPD) and non-invasive disease - will increase. We built a dynamic transmission model to investigate this question. The model predicted that a 1 + 1 schedule would incur 8777-27 807 additional cases of disease and 241-743 more deaths over 5 years. Serotype 19A caused 55-71% of incremental IPD cases. Scenario analyses showed that booster dose adherence, effectiveness against carriage and waning in a 1 + 1 schedule had the most influence on resurgence of disease. Based on the model assumptions, switching to a 1 + 1 schedule will substantially increase disease burden. The results likely are conservative since they are based on relatively low vaccine-type pneumococcal transmission, a paradigm that has been called into question by data demonstrating an increase of IPD due to several vaccine serotypes during the last surveillance year available.

Infant 13-valent pneumococcal conjugate vaccination (PCV13) was introduced to the UK in 2010. Its impact on serotypes implicated in adult non-bacteraemic pneumococcal pneumonia is not known. Beginning in 2008, a 5-year prospective cohort study of adults admitted to hospital with community-acquired pneumonia (CAP) was conducted. Pneumococcal serotype was established using a validated multiplex immunoassay (Bio-Plex; Bio-Rad, Hercules, CA, USA). The overall incidence for hospitalised CAP and pneumococcal CAP was 79.9 (95% CI 76.6-83.3) and 23.4 (95% CI 21.6-25.3) per 100,000 population, respectively. A decline in CAP (incidence rate ratio (IRR) per year 0.96, 95% CI 0.94-0.99; p=0.016) and pneumococcal CAP (IRR per year 0.84, 95% CI 0.80-0.89; p<0.001) was observed over the 5-year period of the study. Between the pre- and post-PCV13 periods of the study, the incidence of CAP due to serotypes included in the PCV7 declined by 88% (IRR 0.12, 95% CI 0.08-0.20; p<0.001), and CAP due to the additional 6 serotypes in PCV13 declined by 30% (IRR 0.70, 95% CI 0.51-0.96; p=0.024). Incidence of adult pneumococcal pneumonia declined over the last 5 years, with serotypes included in PCV13 declining post-PCV13 introduction, indicating early herd protection effects from PCV13 infant vaccination on adult non-bacteraemic disease. These effects may accrue over the coming years with implications for national pneumococcal vaccination policies in adults., (Copyright ©ERS 2015.)

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Despite the reduction in adult invasive pneumococcal disease through 'herd protection' consequent to the introduction of childhood pneumococcal conjugate vaccination (PCV), a significant proportion of adults continue to develop pneumococcal pneumonia caused by one of the seven serotypes included in the seven-valent conjugated pneumococcal vaccine (PCV7). The clinical features and outcomes of these adults have not been previously reported., Methods: Adults recruited over a three year period to a large prospective cohort study of community acquired pneumonia (CAP) were investigated for pneumococcal serotypes using a validated multiplex immunoassay (Bio-plex). The baseline characteristics and outcomes of adults with PCV7-serotype CAP in comparison to those with non-PCV7-serotype CAP were established., Results: Pneumococcal aetiology was identified in 415 of 1166 (35.6%) individuals, and a serotype determined in 287 (69.2%). Following exclusion of three individuals with both a PCV7 and non-PCV7 serotype, 77 of the remaining 284 (27.1%) adults had CAP due to PCV7 serotypes. Adults with PCV7-serotype CAP were older (median years (inter-quartile range) 73.3 (60.8-84.4) versus 65.0 (46.1-78.0); p=0.001) and were more likely to have a World Health Organisation performance status ≥1 (odds ratio (OR) 2.05, 95% confidence interval (CI) 1.21-3.50).The presence of stroke (adjusted OR 2.84, 95% CI 1.36-5.95) and dementia (adjusted OR 3.55, 95% CI 1.26-9.94) as underlying co-morbid illnesses were independently associated with PCV7-serotype CAP; 30-day mortality was significantly greater in adults with PCV7-serotype CAP (adjusted OR 4.38, 95% CI 1.85-10.34)., Conclusion: A significant proportion of adults continue to develop PCV7-serotype CAP in the era of childhood pneumococcal conjugate vaccination. These adults are more likely to have stroke and dementia as underlying co-morbid illnesses, and have a higher 30-day mortality. A combination of pneumococcal transmission factors, host factors and pneumococcal serotype specific characteristics are likely to explain these findings., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: On a population level, pneumococcal conjugate vaccination in children has reduced the incidence of vaccine-type disease in all age groups, including older adults. Few individual level studies have been performed describing the pneumococcal serotypes associated with adult community acquired pneumonia (CAP) and quantifying associations with child contact and child vaccination status., Methods: Pneumococcal serotypes were determined using a validated multiplex immunoassay (Bio-Plex) in a large prospective cohort of adults hospitalised with CAP. Child (<16 years old) contact history and child pneumococcal vaccination status were obtained from patients and public health records, respectively., Results: Of 1130 participants, 329 (29.1%) reported child contact, and pneumococcal infection was identified in 410 (36.3%). Pneumococcal CAP was commoner in adults with child contact (148/329 (45.0%) vs 262/801 (32.7%); adjusted OR 1.63, CI 1.25 to 2.14; p<0.001). A serotype was determined in 263 of 410 (64.1%) adults with pneumococcal CAP; 112 (42.6%) reported child contact, 38 (33.9%) with a vaccinated child. Adults in contact with a vaccinated child were significantly less likely to have vaccine-type CAP compared with adults in contact with an unvaccinated child (6 of 38 (15.8%) vs 25 of 74 (33.8%), respectively; OR 0.37, 95% CI 0.14 to 0.99; p=0.044)., Conclusions: Pneumococcal aetiology in adult CAP is independently associated with child contact and implicated serotypes are influenced by child vaccination status. This is the first study to demonstrate these associations at an individual rather than population level; it affirms that 'herd protection' from childhood vaccination extends beyond adult invasive disease to pneumococcal CAP.

Background: Protracted bacterial bronchitis is a major cause of persistent cough in childhood. The organisms most commonly isolated are nontypable Haemophilus influenzae and Streptococcus pneumoniae . There are no studies addressing typing of these organisms when recovered from the lower airways., Methods: Isolates of these two organisms (identified in BAL samples from children undergoing routine investigation of a chronic cough thought to be attributable to a protracted bacterial bronchitis) were subject to typing. Samples were collected in Sheffield, England, and Athens, Greece. The majority of the children from Sheffield had received pneumococcal-conjugate vaccines 7 or 13 (PCV-7 or PCV-13) conjugate vaccine but only a minority of Greek children had received PCV-7., Results: All 18 S pneumoniae isolates from Greek BAL samples are serotypes contained in PCV-13 while 10 are contained in PCV-7. In contrast, 28 of the 39 samples from Sheffield contained serotypes that are not included in PCV-13. All 26 of the nontypable H influenzae samples obtained in Sheffield produced distinct multilocus variable-number tandem repeat analysis profiles. There was a significant difference between children from Athens and Sheffield in the distribution of serotypes contained or not contained in the pneumococcal vaccine ( P = .04). More specifically, immunization with pneumococcal vaccine was related with isolation of S pneumoniae serotypes not included in the vaccine (OR, 0.021; CI, 0.003-0.115; P < .001)., Conclusions: The data suggest that both vaccine and nonvaccine S pneumoniae serotypes may play a role in protracted bacterial bronchitis and provide some hints that serotype replacement may occur in response to the introduction of conjugate vaccines.

Objectives: To examine invasive pneumococcal disease (IPD) incidence, the impact of the 7-valent pneumococcal conjugate vaccines (PCV7s) programme on the distribution of Streptococcus pneumoniae serotypes and risk factors for IPD among HIV-positive adults., Methods: We analysed adults (aged ≥15 years) reported to the HIV and IPD national datasets in England and Wales (2000-2009). Through data-linkage, changes in IPD incidence and serotype distribution were examined. Risk factors for IPD among HIV-positive adults were assessed using a case-control study., Results: Among 63,109 HIV-positive adults, 951 were co-infected with IPD. The average annual incidence of IPD was 245 episodes per 100,000 HIV-positive adults and 246 of 100,000 among those aged 15-44 years. Incidence was higher among those not on antiretroviral therapy (ART) (281 of 100,000) and those with severe immunosuppression (563 of 100,000). Among 9283 adults aged 15-44 at IPD diagnosis, 2.4% were living with undiagnosed HIV. The proportion of IPD episodes in HIV-positive adults with serotypes covered by PCV7 was 23% in 2009, a 54% proportional reduction compared with pre-PCV7 (2000-2006); the reduction in adults of unknown HIV status was 70%. The proportion of IPD episodes among HIV-positive adults caused by serotypes covered by PCV13 was 61%. Significant risk factors for IPD in multivariate analysis included older aged (≥65 years), a lower nadir CD4 cell count and no previous ART., Conclusion: An HIV test should be offered and recommended to adults aged 15-44 years without other obvious IPD risk factors. Our study provides an evidence base to policy makers regarding the use of the new PCV13 in HIV-positive adults.

A pneumococcal conjugate vaccine (PCV7) was introduced into the United Kingdom's childhood immunisation schedule in September 2006. Evaluation of its impact on the incidence of invasive pneumococcal disease (IPD) as assessed by routine reports of laboratory-confirmed cases should take into account possible long-term trends due to factors like changes in case ascertainment. To this end, we compared pre-PCV7 trends in reported IPD incidence in England and Wales identified by blood culture with those for two other bacteraemias, Escherichia coli and non -pyogenic streptococci, for which there has not been any public health intervention. While no trend was detected in the age group 65 years and older, there was an annual increase of 3% and 11% in those aged under five years and between five and 64 years, respectively, which was similar for IPD and the other two pathogens. After PCV7 introduction, a continuing trend was only found for non-pyogenic streptococci in under five year-olds. These trends in the incidence for bacteraemias for which there has been no intervention could suggest that there have been changes in case ascertainment because of increased reporting or blood culturing. Accounting for them will improve the evaluation of the impact of PCV7 on IPD.

Streptococcus pneumoniae strains causing invasive pneumococcal disease (IPD) in the elderly population of England and Wales during the winter of 2003/2004 (1 November 2003 to 30 April 2004) were characterized by serotyping and genotyping in order to determine their population structure in the elderly. Serotyping and multilocus sequence typing (MLST) were carried out on 542 invasive isolates referred to the Respiratory and Systemic Infection Laboratory. Pneumococci were distributed among 32 serotypes and 144 MLST sequence types. A high genetic diversity was observed within the major serotypes. Genetic relatedness varied with regard to serotype. Isolates within serotypes 3, 7F and 8 were the most genetically related whereas serotypes 6A and 19F comprised isolates originating from unrelated ancestors. There was indirect evidence that some pneumococci were derived from clones that had undergone capsular switching in the past. Interestingly one case of IPD was caused by a pneumococcus originating from a clone that had undergone capsular switching from serotype 18C, a serotype included in 7-valent pneumococcal conjugate vaccine (PCV) to serotype 1 (serotype not included in PCV) suggesting that virulent clones with the potential ability to evade PCV existed in the pneumococcal population prior to the routine introduction of this vaccine. Isolates from 28 cases of apparent 23-valent pneumococcal polysaccharide vaccine (PPV) failure were included but there was no evidence of the emergence of particular clones associated with vaccine failures. Longitudinal studies based on serotypic and genetic characterization of pneumococci are fundamental to understanding the impact of both PPV and PCV on the genetic structure of pneumococcal populations.

Following the introduction of the pneumococcal 7-valent conjugate vaccine (PCV7) into the routine infant immunization schedule in England, Wales, and Northern Ireland, pneumococcal serotype-specific immunoglobulin G (IgG) antibody testing was offered as a clinical service to all children within the program with invasive pneumococcal disease (IPD) to confirm an adequate antibody response to PCV7. As of March 2008, serum samples taken within 14 to 90 days of vaccination had been submitted from 107 children who had received one or more doses in the second year of life. Sera were assayed by a multiplexed microsphere assay incorporating both cell wall polysaccharide and serotype 22F adsorption. A protective serotype-specific antibody level was defined as a concentration of > or = 0.35 microg/ml. Eight children failed to develop a response to their infecting serotype (6B [n = 4], 18C [n = 2], 4 [n = 1], and 14 [n = 1]), despite receiving at least three doses of PCV7 in the second year of life or two doses in the second and two or three in the first year of life. A further two children were nonresponsive to a serotype (6B) different than that causing disease. None of the 10 children had a clinical risk factor for IPD. Two had marginally low levels of total serum IgG but mounted adequate responses to the other six PCV serotypes. This serotype-specific unresponsiveness may reflect immune paralysis due to large pneumococcal polysaccharide antigen loads and/or a potential genetic basis for nonresponse to individual pneumococcal serotypes.