Herpes zoster (HZ) virus, or shingles, is the reactivation of the same virus that causes chickenpox Since many people get chickenpox when they are children, the incidence of HZ is high in adults, particularly in older individuals. Early case reports from patients experiencing stroke after a HZ zoster infection show the presence of the virus in biopsies of blood vessels present in brain tissue. This suggests that HZ virus was the cause of their stroke. Furthermore, several research studies have observed an increased risk of stroke after contracting HZ infection. The risk is around two-fold higher 1-2 weeks post-HZ infection, but no longer detectable by one year after the initial infection. Treatment of HZ virus with antivirals was shown to be inconclusive in terms of lowering stroke risk. Since 2013, NHS England has a programme to offer HZ vaccines to patients aged 70-80 years. Whilst effective at reducing the incidence of HZ in the vaccinated, it is unknown whether the HZ vaccines are also effective at lowering stroke risk. Our aim is to investigate in CPRD and linked hospital records whether the rate of stroke is lower in patients in their 70s who took the HZ vaccine compared to matched patients in their 70s just before the vaccination programme began.
Background: Millions of people are affected each year by herpes zoster (HZ) infection worldwide. The incidence of HZ is 3-5 people for every 100,000 people in North America, Europe and Asia and is increasing with time, likely related to a decrease in T-cell immunity with aging and immunosuppression. Our team observed HZ to be associated with a short-term increased risk of stroke in a previously conducted meta-analysis. We aim to investigate whether HZ vaccine is associated with decreased stroke incidence in those aged in their 70s and vaccinated compared to patients in their 70s before the vaccination programme began.
Population: Patients aged 70-80 years during 2007-2019 registered in GP practices in England with linkage to HES APC, ONS mortality and IMD data. Patients will be excluded with a stroke history or registered with their GP for less than 12 months.
Intervention: First Zostavax vaccination (index date) between September 2013 and December 2019.
Comparator: No Zostavax vaccination. We will match each exposed patient to a patient of the same sex and age in 2007-2012 (and assign the month/day of the exposed patient as the index date for the unexposed).
Outcome: First stroke diagnosis. Secondary outcomes are stroke/TIA and myocardial infarction.
Methods: Patients will be followed until the first of: death, stroke diagnosis, leaving the GP practice, 30 days before last GP practice data collection, 1st March 2020, or five years after the index date. Unexposed patients who later received the HZ vaccine were also censored on that date (and become eligible for the exposed group). Cox proportional hazards regression will be used to estimate hazards ratios for incident stroke for those vaccinated compared to those not vaccinated in the subsequent 5 years, adjusting for potential confounders and estimating robust standard errors.
Primary Outcome:
Stroke
Secondary Outcomes:
A) Stroke or TIA
B) Myocardial infarction
Kathryn Richardson - Chief Investigator - University of East Anglia
Kathryn Richardson - Corresponding Applicant - University of East Anglia
Fawziah Lalji - Collaborator - University Of British Columbia
Helen McDonald - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Helen Parretti - Collaborator - University of East Anglia
Jemma Walker - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Yoon Loke - Collaborator - University of East Anglia
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation