COMMUNICABLE DISEASE AND PUBLIC HEALTH. VOL 5 NO 3 SEPT 2002

With effect from July 2002 a  l i v e  a t t e n u a t e d varicella-zoster virus (VZV) vaccine has become available for use in the UK. It is currently licensed only for susceptibles over the age of twelve years and younger contacts of highrisk individuals (such as leukaemic children), but there will inevitably be calls for its wider use. However, widespread varicella vaccination has potential knock-on effects, the most important of which is that on the incidence of herpes zoster (shingles).

Hope-Simpson in 1965 w a s the  first to suggest that immunity to shingles could be boosted by exposure to VZV1, and if this were true then the introduction of mass varicella vaccination would remove this stimulus and lead to a rising incidence of herpes zoster.

Three questions therefore arise. Does exposure to VZV really help prevent or delay the development of zoster? If so, how substantial is this effect? And, finally, how big an increase in zoster should be expected after widespread introduction of varicella immunisation?

The recent publication of two very different epidemiological studies, one in The Lancet2 and one in Vaccine3 go a long way to help us answer these questions. The first study compared 244 cases of recently diagnosed herpes zoster to controls with no history of shingles that were matched by age, sex and general practice. Patients and controls were interviewed regarding their contacts with varicella cases or children (assumed to be a proxy for exposure to VZV) over the previous 10 years.

The results were striking: exposure to VZV (or children) was significantly protective against zoster. The degree of protection increased with exposure, so that the risk of developing zoster in the most heavily exposed group was less than one fifth that in the unexposed group (figure 1). The Vaccine paper3, by contrast, analysed a large, prospective, oneyear survey of morbidity recorded by general practitioners in England and Wales. There were 1,595 cases of zoster recorded in this survey along with data on their socioeconomic status, ethnicity and the household composition of the participants, including whether they lived with children or not. The authors found that exposure to varicella was greater in adults living with children and that this exposure was highly protective against zoster, lasting, on average, 20 years (95% confidence interval: 7-41 years). Remarkably, these two very different epidemiological surveys give not only qualitatively but quantitatively similar results (figure 1). Prior to these studies, and despite the long interval since Hope- Simpson's hypothesis was published, only a few papers had reported evidence suggesting that exposure to VZV protects against zoster.

A Japanese study found that the incidence of zoster was 50-85% lower among paediatricians and family practitioners than the general public4; increased immunity to VZV was observed in individuals exposed to varicella cases5; and a study among vaccinated leukaemic children suggested that household exposure to varicella was highly protective against zoster6. The two recent studies substantially strengthen these findings and, taken together, they provide compelling evidence that exposure to varicella provides long-term protection against zoster in many otherwise healthy individuals. What are the implications of this for varicella vaccination? A number of mathematical models have addressed this issue3,7-9, though only one3 has been parameterised using the recent epidemiological data. Nevertheless, the models have given consistent answers when concentrating on the scenarios that were subsequently found to be realistic3. Overall zoster incidence should increase by 30 to 50% if varicella vaccine coverage is high, and then gradually fall3,7,8. The increase will be due to the loss of boosting from varicella, and the more effectively varicella is c o n t r o l l e d ( f o r i n s t a n c e b y implementing a campaign) the greater the increase in zoster incidence will be. The eventual fall in zoster incidence will occur because vaccinated cohorts will replace the naturally infected cohorts and the vaccine strain is less likely to reactivate than the wild type10. The period of elevated zoster incidence is expected to last for 30 to 50 years and will affect most those aged 10-44 years at the introduction of vaccination3. Because the morbidity accompanying a case of zoster is considerably greater than varicella (the average number of quality adjusted life-years lost is more than 10-fold higher for zoster cases than for varicella cases11,12), such an increase would have very serious consequences for public health, cancelling out the benefit of reduced varicella incidence. This, then, is the prediction, but is there any evidence of it actually h a p p e n i n g w h e r e v a r i c e l l a vaccination has already been introduced? In the United States, which started vaccinating in 1995, the incidence of varicella appears to have declined dramatically13, even in those that have not been vaccinated14. However, there have been no published longitudinal studies on the incidence of zoster. Countries considering the introduction of varicella vaccination urgently need these data. The impressive reduction in chickenpox incidence observed in the US may be a double-edged sword, foreshadowing a correspondingly large increase in zoster over the next few decades unless other steps a r e t a k e n t o p r e v e n t t h i s . Unfortunately, no such measures are currently available, though vaccine trials to prevent zoster are underway in the US15. It may be wiser to delay a decision on the widespread use of varicella vaccine until a means of protecting adults from shingles has been found.

COMMUNICABLE DISEASE AND PUBLIC HEALTH
VOL 5 NO 3 SEPTEMBER 2002