One of the most fascinating facts about varicella zoster virus, which causes chickenpox and, in its reactivated form, shingles, is that the immunity of a latently infected person appears to be “boosted” if they are in contact with a case of chickenpox. This idea that contact with children with chickenpox boosts immunity to shingles was first described by Edgar Hope-Simpson in 1965. A celebrated GP researcher and epidemiologist, Hope-Simpson was also the first to show that chickenpox and shingles were caused by the same virus.
His “exogenous boosting” hypothesis is one of the key reasons that we do not vaccinate children against chickenpox in the UK. The concern is that removing chickenpox from the population, through a universal vaccination programme, will remove all this helpful immune boosting for adults, and cause an increase in shingles. Since Hope-Simpson’s 1965 paper, epidemiologists have provided further evidence for this “boosting” effect. However, the nature of the boosting effect has been subject to significant debate and modelling studies to inform chickenpox vaccination programmes, and we have been forced to make assumptions about the magnitude and duration of the boosting effect.
Furthermore, it was also clear that for many experts, real world evidence did not substantiate the exogenous boosting effect. The United States introduced a universal single-dose varicella vaccine programme for children aged 12 to 18 months in 1995 and changed in 2006 to a two-dose schedule to improve vaccine effectiveness. Since then, the US has not observed an “epidemic” of shingles cases, as predicted by some modelling work. A great deal of debate has ensued, with very mixed evidence regarding whether the incidence of shingles has increased in the US and whether any increase in incidence occurred prior to, or following, the vaccine’s introduction.
As such, we considered whether routinely collected health data and newer epidemiological methods could help shed light on this, often controversial, topic. The “self-controlled case series” is a relatively new study design for epidemiologists. It is a “case-only” design, meaning it only includes people who have had the outcome and the exposure. In any experiment, when you are trying to investigate the effect of a factor like exposure to chickenpox, you want the comparison groups to be as similar as possible. In our study, rather than compare the effect of chickenpox exposure across different groups of people, who might have different characteristics e.g. different behaviours or health status, we used people as their own controls in different time periods. The design was also particularly useful for this question, as it would have been impossible to identify truly unexposed individuals; a large number of children with chickenpox may never have their episode recorded in GP records, as parents can and do self-manage the condition without any healthcare intervention.
We showed that adult exposure to a child with chickenpox does lower the risk of shingles for up to 20 years, but does not provide full protection; in our study, the risk reduction was around 30%. Current UK cost effectiveness modelling studies for routine chickenpox vaccination assume that adult exposure to chickenpox provides complete protection against shingles for between two and 20 years. Although our research should not on its own determine specific vaccination schedules, it suggests that cost effectiveness modelling studies for routine chickenpox vaccination may need updating.
Harriet Forbes, assistant professor, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine.
Liam Smeeth, professor, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine.
Charlotte Warren-Gash, associate professor, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine.
Competing interests: None declared