Streptococcus pneumoniae is a bacterium which is normally found in the human nasal passages and often remains there without causing disease. Occasionally it invades the body to cause septicaemia and meningitis, and it is the most common cause of pneumonia in adults. Consequently pneumococcal disease results in a significant burden of disease in the UK, especially in the very young and in older adults. Rates of pneumococcal disease fell in adults and children from 2006, after routine childhood vaccination against pneumococcus was introduced. However recent data suggest rates are rising again, especially amongst adults over the age of 65 years. A single-dose of a different pneumococcal vaccine is offered to adults in the UK from 65 years old, however it is not clear how effective this vaccine is for preventing pneumococcal disease. We aim to establish whether giving a booster dose of this vaccine to over 65 year olds prevents pneumococcal disease (including pneumonia requiring hospital admission, pneumonia in the community, and meningitis or septicaemia caused by Strep pneumoniae) by comparing disease rates in patients who have had 1 versus 2 or more doses. We will also describe the characteristics of patients receiving 1 versus 2 or more doses. Additionally, we will investigate interactions between combinations of pneumococcal vaccine, an inactivated vaccines and the live shingles vaccines for any non-specific health benefits. This study will allow us to understand current vaccination practice, and will inform future vaccination policy.
Objective: To evaluate the effectiveness of multiple doses of the polysaccharide vaccine (PPV23) for preventing pneumococcal disease, hospitalisations and deaths in ?65 year olds.
Methods: We will perform an historical cohort study using routinely collected health surveillance data. We will use the Clinical Practice Research Datalink (CPRD) to extract a cohort of ?65 year olds between 2006 and 2018 who have received at least one PPV23 dose. We will use CPRD data and Health Episode Statistics (HES) discharge diagnosis coding to establish pneumococcal disease events including hospitalised pneumonia, hospitalised Invasive Pneumococcal Disease and pneumonia in primary-care. Possible cofounders will be identified from CPRD database including pneumococcal clinical at risk conditions, smoking status, alcohol misuse, frailty and influenza and shingles vaccine status. Furthermore we will investigate possible heterologous effects associated with the interaction between inactivated pneumococcal and live shingles vaccine, through the measurement of all-cause mortality (recorded in CPRD) and hospitalisation rates for any cause.
Data Analysis:
We will described the characteristics of patients receiving 1 versus 2+ PPV23 doses including age, geography, presence of comorbidity, month and year. We will run a comparison of disease rates between patients who have received 1 versus 2+ doses of PPV23. For investigating heterologous effects of combinations of live and inactivated vaccines we will compare mortality and hospitalisation rates in patients who have received 1+ doses of PPV23 only with those received 1+ doses of PPV23 and 1+ doses of shingles vaccine.
Hazard ratios will be derived from a cox regression time-to-event analysis and incidence rate ratios from multi-variable Poisson regression (IRR) and we will incorporate multi-level random effects to account for the time-varying variables. Hazard ratios and IRR will be used as measures of vaccine effectiveness.
Primary outcomes: Pneumonia hospitalisation.
Secondary outcomes: Invasive Pneumococcal Disease (IPD) hospitalisation; primary care pneumonia consultations; all-cause hospitalisation; all-cause mortality
Neil French - Chief Investigator - University of Liverpool
Klara Doherty - Corresponding Applicant - University of Liverpool
Daniel Hungerford - Collaborator - University of Liverpool
Kate Fleming - Collaborator - University of Liverpool
Laura Bonnett - Collaborator - University of Liverpool
Natalie Beveridge - Collaborator - University of Liverpool
Valerie Decraene - Collaborator - Public Health England
Dan Hungerford - Collaborator - University of Liverpool
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation