Dataset Information

Using the indirect cohort design to estimate the effectiveness of the seven valent pneumococcal conjugate vaccine in England and Wales.

ABSTRACT:

Background

The 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2, 3 and 13 month 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.

SUBMITTER: Andrews N

PROVIDER: S-EPMC3229580 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Using the indirect cohort design to estimate the effectiveness of the seven valent pneumococcal conjugate vaccine in England and Wales.

Andrews Nick N Waight Pauline A PA Borrow Ray R Ladhani Shamez S George Robert C RC Slack Mary P E MP Miller Elizabeth E

PloS one 20111202 12

<h4>Background</h4>The 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2, 3 and 13 month 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.<h4>Methods and findings</h4>We used enhanced surveillance data, collated at the Health Protection Agency, on vaccine type (n = 153) and non vaccine t ...[more]

PMID: 22164292

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Project description:Understanding the epidemiology of pneumococcal co-colonization is important for monitoring vaccine effectiveness and the occurrence of horizontal gene transfer between pneumococcal strains. In this study we aimed to evaluate the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal co-colonization among Portuguese children. Nasopharyngeal samples from children up to 6 years old yielding a pneumococcal culture were clustered into three groups: pre-vaccine era (n?=?173), unvaccinated children of the vaccine era (n?=?169), and fully vaccinated children (4 doses; n?=?150). Co-colonization, serotype identification, and relative serotype abundance were detected by analysis of DNA of the total bacterial growth of the primary culture plate using the plyNCR-RFLP method and a molecular serotyping microarray-based strategy. The plyNCR-RFLP method detected an overall co-colonization rate of 20.1%. Microarray analysis confirmed the plyNCR-RFLP results. Vaccination status was the only factor found to be significantly associated with co-colonization: co-colonization rates were significantly lower (p?=?0.004; Fisher's exact test) among fully vaccinated children (8.0%) than among children from the pre-PCV7 era (17.3%) or unvaccinated children of the PCV7 era (18.3%). In the PCV7 era there were significantly less non-vaccine type (NVT) co-colonization events than would be expected based on the NVT distribution observed in the pre-PCV7 era (p?=?0.024). In conclusion, vaccination with PCV7 resulted in a lower co-colonization rate due to an asymmetric distribution between NVTs found in single and co-colonized samples. We propose that some NVTs prevalent in the PCV7 era are more competitive than others, hampering their co-existence in the same niche. This result may have important implications since a decrease in co-colonization events is expected to translate in decreased opportunities for horizontal gene transfer, hindering pneumococcal evolution events such as acquisition of antibiotic resistance determinants or capsular switch. This might represent a novel potential benefit of conjugate vaccines.

Project description:BACKGROUND:Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ?65 years. METHOD:A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results. RESULTS:The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ?65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust. CONCLUSIONS:Vaccinating immunocompetent individuals aged ?65 years with PCV13 is efficacious. However the absolute incidence of vaccine-type disease will likely become very low due to wider benefits of the childhood PCV13 vaccination programme, such that a specific PCV13 vaccination programme targeting the immunocompetent elderly would not be cost-effective.

Project description:ObjectiveTo estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine.DesignEconomic evaluation using a cohort model from the perspective of healthcare providers.SettingEngland.ParticipantsPeople aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes.Main outcome measuresCosts, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios.ResultsIncreasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions--that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme--the incremental cost effectiveness ratio was estimated to be more than £30,000 (€37,216; $48,210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates.ConclusionUnder base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non-bacteraemic pneumococcal pneumonia, particularly in at risk groups.

Project description:BACKGROUND:In October 2017, the United Kingdom Joint Committee on Vaccination and Immunisation (JCVI) recommended removal of one primary dose of the 13-valent pneumococcal conjugate vaccine (PCV13) from the existing 2+1 schedule (2, 4, 12 months). We conducted a mathematical modelling study to investigate the potential impact of a 1+1 (3, 12 month) schedule on invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Our results and those from a 1+1 immunogenicity study formed the key evidence reviewed by JCVI. METHODS AND FINDINGS:We developed age-structured, dynamic, deterministic models of pneumococcal transmission in England and Wales to describe the impact on IPD of 7-valent PCV (PCV7; introduced in 2006) and PCV13 (introduced in 2010). Key transmission and vaccine parameters were estimated by fitting to carriage data from 2001/2002 and post-PCV IPD data to 2015, using vaccine coverage, mixing patterns between ages, and population data. We considered various models to investigate potential reasons for the rapid increase in non-PCV13 (non-vaccine serotype [NVT]) IPD cases since 2014. After searching a large parameter space, 500 parameter sets were identified with a likelihood statistically close to the maximum and these used to predict future cases (median, prediction range from 500 parameter sets). Our findings indicated that the emergence of individual NVTs with higher virulence resulting from ongoing replacement was likely responsible; the NVT increase was predicted to plateau from 2020. Long-term simulation results suggest that changing to a 1+1 schedule would have little overall impact, as the small increase in vaccine-type IPD would be offset by a reduction in NVT IPD. Our results were robust to changes in vaccine assumptions in a sensitivity analysis. Under the base case scenario, a change to a 1+1 schedule in 2018 was predicted to produce 31 (6, 76) additional IPD cases over five years and 83 (-10, 242) additional pneumococcal-CAP cases, with together 8 (-2, 24) additional deaths, none in children under 15 years. Long-term continuation with the 2+1 schedule, or changing to a 1+1, was predicted to sustain current reductions in IPD cases in under-64-year-olds, but cases in 65+-year-olds would continue to increase because of the effects of an aging population. Limitations of our model include difficulty in fitting to past trends in NVT IPD in some age groups and inherent uncertainty about future NVT behaviour, sparse data for defining the mixing matrix in 65+-year-olds, and the methodological challenge of defining uncertainty on predictions. CONCLUSIONS:Our findings suggest that, with the current mature status of the PCV programme in England and Wales, removing one primary dose in the first year of life would have little impact on IPD or pneumococcal CAP cases or associated deaths at any age. A reduction in the number of priming doses would improve programmatic efficiency and facilitate the introduction of new vaccines by reducing the number of coadministered vaccines given at 2 and 4 months of age in the current UK schedule. Our findings should not be applied to other settings with different pneumococcal epidemiology or with immature programmes and poor herd immunity.

Dataset Information

Using the indirect cohort design to estimate the effectiveness of the seven valent pneumococcal conjugate vaccine in England and Wales.

Background

Methods and findings

Conclusions

Publications

Using the indirect cohort design to estimate the effectiveness of the seven valent pneumococcal conjugate vaccine in England and Wales.

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