The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England

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Summary

Objective

To inform national policy making on the use of the 13-valent pneumococcal vaccine among risk groups we estimated the increased risk of invasive pneumococcal disease (IPD) outcomes among clinical risk groups. Three years of post 7-valent pneumococcal conjugate vaccine (PCV7) data was included to investigate the herd protection effects.

Methods

Over 22,000 IPD patients in England (March 2002–March 2009 – aged 2 and over) were linked to their hospitalisation records. The prevalence of risk factors in these patients was compared to the prevalence of risk factors in the general population.

Results

There was an increased odds ratio (OR) for hospitalisation (OR 11.7 2–15 years; 7.6 16–64; 2.7 65+) and death (OR 2.4 2–15 years, 3.9 16–64, 1.2 65+) from IPD among risk group. The most important risk factors that predict IPD are chronic liver disease, immunosuppression, and chronic respiratory diseases. Herd protection effects due to introduction of the 7-valent vaccine were identical in both patient groups as shown by the similar decline in the proportion of IPD caused by PCV7 serotypes in risk and non-risk groups.

Conclusions

There is a marked increased risk of IPD among those with certain clinical conditions, suggesting potential benefit from a targeted vaccination approach. However, the indirect protection from conjugate vaccination of children suggests PCV vaccination of high-risk groups may not provide substantial additional benefit once herd immunity takes effect.

Introduction

Development of evidence-based guidelines for the prevention of infectious disease by vaccination requires an understanding of the population groups most likely to become infected or to have severe disease or worse outcomes. Identification of high-risk groups allows a selective vaccination programme to be employed, as exemplified by the targeting of vaccination in the recent H1N1 (2009) pandemic to the most vulnerable.1, 2 The 23-valent pneumococcal polysaccharide (PPV23) vaccine has been recommended in the UK since 19923 for prevention of invasive pneumococcal disease (IPD) in those with various clinical conditions considered to be at increased risk of IPD4 though uptake has been low.3 There is however limited evidence on the magnitude of the increased risk for these various clinical groups by age compared with the general population. Moreover, there is little information on the degree and duration of protection from PPV23 in these targeted high-risk groups.5, 6 Pneumococcal conjugate vaccines (PCVs) that are more immunogenic than PPV23 may provide a better alternative for protection of high-risk patients.7, 8, 9 However, they are more costly10 and cover a lower proportion of the serotypes causing IPD than PPV23.

To help evaluate the potential utility of offering the 10-valent (PCV10) or 13-valent (PCV13) conjugate vaccine to individuals in high-risk groups, we identified patients with IPD admitted to hospital in England and compared the prevalence of risk factors in this group with that in the general population. Among the hospitalised patients with IPD we compare the case fatality ratio and the serotype distribution before and after the introduction of PCV7 in September 2006 and the coverage that would be achieved with higher valency vaccines for patients with high-risk conditions compared to those without.

Section snippets

Ascertainment of risk factors in the general population

Information on the prevalence of clinical risk factors in the general population was estimated from a Department of Health (DH) survey of the uptake of PPV23 using data extracted from 55.6% of the general practices in England, together covering 60% of the population.11, 12, 13 Risk groups recommended for PPV23 vaccination in the Green Book (Immunisation Against Infectious Disease)4 were identified from the diagnostic codes14 used to record clinical conditions and medication in the electronic

Prevalence of risk factors in the general population

The largest risk group in England are those with chronic heart disease, with just over 3 million patients (Table 2); patients with cochlear implants was the smallest with around 3,500 patients. Overall, 13% of the general population had one or more risk factors, and 45% in those aged 65 years and over. Of the total patients in a risk group, 59% were aged 65 years and over.

Linkage success

Of the 38,055 patients aged over 2 years in the national IPD dataset in the study period, 22,298 (59%) could be linked to a

Discussion

Our study confirms the elevated risk of IPD in those with underlying clinical conditions for whom PPV23 vaccination is currently recommended. Both the incidence of infection and the case fatality rate are increased, especially among the immunocompromised, and those with chronic respiratory conditions or liver disease. A high proportion of the liver disease in adults (73%) was alcohol related, suggesting that life style rather than hepatic problems per se may have been implicated in the

Funding

This work was supported by the UK Department of Health Policy Research Programme, grant number: 039/0031 to AJvH and JS. The views expressed in the publication are those of the authors and not necessarily those of the Department of Health.

Conflict of interest

AJvH, no conflict; NA, no conflict; PAW, no conflict; JS, no conflict; PG, no conflict; RG, has received assistance to attend scientific meetings from Wyeth (Pfizer) and GlaxoSmithKline, and his laboratory has received research funding from Wyeth (Pfizer) and GlaxoSmithKline; EM, no conflict.

Ethic approval

The Health Protection Agency has approval under PIAG Section 60 of the Health and Social Care Act 2001(now subsumed into the National Information Governance Board for Health and Social Care with Section 60, now Section 251 of the NHS Act 2006) to process confidential patient information for the purposes of monitoring the efficacy and safety of vaccination programmes.

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