This work is part of the NIHR-funded MEMVIE project.

Pneumococcal disease is caused by the bacterium Streptococcus pneumoniae (pneumococcus). There are more than 90 different pneumococcal types (serotypes) that can cause disease in humans. Infections are either non-invasive (occurring outside the major organs or the blood and tend to be less serious) or invasive (occurring inside a major organ or the blood and tend to be more serious). Invasive pneumococcal disease is a major cause of disease and death globally and in the UK. Particularly vulnerable are those with weakened immune systems, the very young and the elderly.

As part of the national immunisation programme, two different pneumococcal vaccines are routinely used. These are the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). PCV13 is currently recommended for infants from two months of age as part of the routine childhood immunisation schedule. A reinforcing (booster) dose of PCV13 is recommended on or after the first birthday. Adults over 65 years and at-risk groups aged two years or over are typically administered PPV23.

Work by the MEMVIE team began with a large systematic review and meta-analysis on global indirect effects of pneumococcal vaccination and this work has been published. The systematic review and meta-analysis study was followed by the development of an individual-based model of post-pneumococcal vaccine epidemiology in England and Wales. Modelling pneumococcal disease is complicated by multiple factors: there are many interacting serotypes; there is a mismatch between carriage (which is epidemiologically important for capturing transmission) and disease; there is very limited information on carriage and this is often from biased sources. For that reason, nuanced transmission models of pneumococcal carriage and disease are required to capture post-pneumococcal vaccine epidemiology in England and Wales. Continual model refinements are being made to ensure the incorporation of all biological processes and assumptions to produce the observed invasive pneumococcal disease incidence data for England and Wales, particularly the timing and magnitude of serotype replacement.

Alongside the development of the epidemiological model, two studies have been undertaken to inform future economic analyses. The first was a systematic review on health utilities/preference-based outcomes, cost/resource use or economic consequences associated with any aspect of pneumococcal disease, and economic evaluations of interventions for pneumococcal disease. The second study, through analysis of Hospital Episode Statistics (HES) administrative data, explores the time trends of pneumococcal disease hospital admissions between 2003 and 2015 in England and establishes the cost of hospital care for pneumococcal infections.

The epidemiological variables and parameters derived from HES data and systematic reviews will form part of the inputs to the health economic model, which will be coupled to the epidemiological model to carry out cost-effectiveness analyses for the spectrum of vaccine scenarios under consideration and address specific policy questions.

Associated publications

1. Shiri T, Kamran K, Keaney K, Mukherjee G, McCarthy ND & Petrou S. Economic aspects of pneumococcal disease: a systematic literature review. (2019) Value in Health 22(11): 1329-1344. doi: 10.1016/j.jval.2019.06.011
2. Shiri T, McCarthy ND & Petrou S. (2019) The impact of childhood pneumococcal vaccination on hospital admissions in England: A whole population observational study. BMC Infectious Diseases 19: 510. doi: 10.1186/s12879-019-4119-8.
3. Nzenze SA, Madhi SA, Shiri T, Klugman KP, de Gouveia L, Moore DP, Karstaedt AS, Tempia S, Nunes MC & von Gottberg A (2017) Imputing the Direct and Indirect Effectiveness of Childhood Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease by Surveying Temporal Changes in Nasopharyngeal Pneumococcal Colonization.Am. J. Epidemiol. 186(4): 435-444. doi: 10.1093/aje/kwx048
4. Shiri T, Datta S, Madan J, Tsertsvadze A, Royle P, Keeling MJ, McCarthy ND & Petrou S (2017) Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis. Lancet Glob. Health. 5(1): e51-e59. doi: 10.1016/S2214-109X(16)30306-0

MEMVIE:

A 6-year project funded by NIHR to provide advice to JCVI.

Researchers involved:

Matt Keeling (Professor, joint between Warwick Mathematics Institute and School of Life Sciences)

Stavros Petrou (Professor in Health Economics, Warwick Medical School)

Graham Medley (Professor, London School of Hygiene and Tropical Medicine)

Sophie Staniszewska (Leader of Patient and Public Involvement, Warwick Medical School)

Martin Underwood (Director of Clinical Trials Unit, Warwick Medical School)

Ed Hill (Postdoctoral researcher, Warwick Mathematics Institute)