Investigating the extent to which exposure to varicella boosts Varicella zoster virus-immunity: a self-controlled case-series, 1997-2018

Date of ISAC Approval: 
08/02/2019
Lay Summary: 
Shingles, also known as herpes zoster, is a painful rash which usually appears in a stripe across the body. It is caused by the same virus that causes chickenpox. After chickenpox, the virus remains in the body. When our immune system is weakened through illness or age, the virus can reactivate to cause shingles. The chickenpox vaccine is not part of routine childhood vaccination in the United Kingdom. This is because there are concerns that removing chickenpox from the population through vaccinating children would cause adults to get shingles. Adults with prior chickenpox exposed to children with chickenpox are thought to have their immunity boosted, therefore reducing their risk of shingles. However, the magnitude of this boosting effect is poorly understood. The objective of this research is to carry out a study using UK healthcare data to estimate the extent to which exposure to children with chickenpox reduces an adult's risk of developing shingles.
Technical Summary: 
Varicella is a common childhood infection caused by the varicella-zoster virus (VZV). After primary VZV infection, the virus remains in the body and zoster is caused by the reactivation of VZV, typically in late-life. The varicella vaccine is not recommended in the United Kingdom, due to concerns that removing varicella contacts from the population through immunisation would lead to an outbreak of zoster cases in adults. Adults exposed to varicella contacts are thought to have their VZV-specific cell-mediated immunity boosted and therefore their risk of zoster reduced. However, the magnitude of this exogenous boosting effect is poorly understood. In countries which universally vaccinate children against varicella, such as the United States, there has been a gradual increase in the rate of zoster since its introduction. However, the dramatic increases in the rate of zoster, as predicted by many modelling studies, have not been observed. This has led some commentators to question whether VZV-boosting from exposure to varicella contacts is as significant as previously thought. This study will use data from the UK to explore the association between having a household member with varicella and the subsequent risk of zoster. Within-person comparisons will be undertaken using the self-controlled case-series method. Participants will have a first-ever diagnosis of zoster and a household member with varicella within the study period. Zoster incidence in periods following varicella exposure will be compared with incidence in other time periods, using conditional Poisson Regression. Age-adjusted incidence ratios (IRs) and 95% confidence intervals (CIs) will be calculated.
Health Outcomes to be Measured: 
Herpes zoster
Collaborators: 

Dr Harriet Forbes - Chief Investigator - London School Of Hygiene & Tropical Medicine (LSHTM)
Professor Adam Finn - Collaborator - University of Bristol
Dr Charlotte Warren-Gash - Collaborator - London School Of Hygiene & Tropical Medicine (LSHTM)
Dr Harriet Forbes - Corresponding Applicant - London School Of Hygiene & Tropical Medicine (LSHTM)
Ian Douglas - Collaborator - London School Of Hygiene & Tropical Medicine (LSHTM)
Judy Breuer - Collaborator - University College London (UCL)
Dr Krishnan Bhaskaran - Collaborator - London School Of Hygiene & Tropical Medicine (LSHTM)
Professor Liam Smeeth - Clinician - London School Of Hygiene & Tropical Medicine (LSHTM)
Sinead Langan - Collaborator - London School Of Hygiene & Tropical Medicine (LSHTM)

Linkages: 
HES Admitted;ONS;Patient IMD;Practice IMD (Standard)