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A study published in PLOS Global Public Health models the public health impact, age-shift, and cost-effectiveness of universal varicella vaccination in Denmark.
Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, past Chair of the BMA Public Health Medicine Committee, said:
Understanding the abstract
“With apologies to those who are already familiar with the terms used, I’ll start by explaining some of what the abstract says. Readers may also wish to read the brief introduction to the diseases caused by the Varicella-Zoster virus at the start of the Green Book chapter on varicella vaccine.2
“This is a modelling study. It starts with some (evidence-based) assumptions about the effects of vaccination, and looks at what you would expect to see with different vaccination regimes assuming that these assumptions hold true.
“The modelling used a “a dynamic transmission model” – this means that it looked at effects, not just on the individuals vaccinated, but in terms of the onward transmission to others. This is particularly important with diseases, like Chickenpox, where being vaccinated typically means you cannot be infected, and thus cannot infect others.
“The abstract states that “The cost-effectiveness of UVV [universal varicella vaccination] was evaluated along with the impact on varicella (including age-shift) and herpes zoster burden.”
“Varicella refers to chickenpox, the disease characterised by a blistering rash. The reference to age-shift refers to the fact that the disease is more likely to be serious in adults. In the absence of a vaccination programme, most people (in temperate climates like the UK) are infected in early childhood. If vaccination is introduced, fewer people have the infectious wild virus, so those who remain unvaccinated are less likely (in any period of time) to encounter an infectious person. Consequently, they may be infected later in life than they would have been in a pre-vaccine era. More serious disease is more likely post-adolescence.
“The reference to herpes zoster burden relates to shingles. Shingles is a late complication of chickenpox. The virus that causes chickenpox – Herpes varicella zoster – commonly persists in the body, in the dorsal root ganglia of the nervous system, where the immune system keeps it harmlessly locked away. If the immune system fails – typically as people age – the virus can escape, travelling down the sensory nerves supplied by that dorsal root ganglion to the “dermatome”; the area of skin supplied by those nerves, causing the characteristic, unilateral, localised (and often very painful) rash. Shingles is generally a more serious condition than childhood chickenpox, so the impact of vaccination on shingles is at least as important as its impact on chickenpox. Benefits from shingles prevention from a chickenpox vaccination programme will, however, take many years to be fully realised, as the majority of the cases prevented would not have occurred until decades later. If the value of future benefits is discounted (as they often are, although this is controversial3-5), this would considerably reduce the benefits of the programme.
“People who are immunosuppressed may have a very serious form of chickenpox, or of shingles, in which the virus is not confined to the one dermatome, but causing more widespread infection, often infecting internal organs as well as the skin (where the rash may resemble primary chickenpox). It is likely, for example, that the composer Gerald Finzi died from encephalitis caused by disseminated shingles.
“The vaccines considered in this study are live-attenuated virus vaccines, in which a modified form of the virus is injected. The virus used, like those used in measles, mumps and rubella vaccines, is “alive” and infectious. (There is some debate as to whether viruses are actually alive at all; but in this context, I mean that it is able to replicate.) It has been “attenuated” – modified so that it is extremely unlikely to cause disease. As it replicates in the body it generates a very good quality, long-lasting immune response. As with MMR vaccine, some people do not respond to a first dose of the vaccine, but the majority of these will respond to a second dose. “Monovalent” vaccines just contain the varicella vaccine; quadrivalent vaccines also contain the measles, mumps and rubella vaccine viruses, providing protection against all four diseases in a single jab.
“It should be noted that the live-attenuated varicella-zoster vaccine virus is not entirely safe: in immune-suppressed individuals it can cause disease.
“Cost-effectiveness analyses compare the cost of the intervention with the net cost of the effects of the intervention (including the costs of the disease prevented, and the cost of any adverse consequences). An intervention is considered cost-effective if the cost per quality adjusted life year – a technical measure of health gain – is below a specific threshold.
“Quite often healthcare economic analyses only consider the benefits (costs avoided) of the intervention to the healthcare system (“payer perspective”). In the UK, the costs and benefits to the NHS (hospitalisations avoided etc) may be considered. With vaccination, however, many of the benefits are much broader than those to the healthcare system, including time taken off work by parents caring for children, the ability of the healthy individual to contribute to society (societal perspective) compared to the reduced ability of somebody impaired by the long-term consequences of a preventable disease, and so on. The introduction of vaccines that would prevent group B Meningococcal disease was based on the value of the vaccine in preventing long-term impairments, for example.6
Other comments
“Serious adverse consequences are uncommon – but when nearly every child has the disease, the number of cases in which adverse consequences arise is large. A few percent of a very large number is a large number.
“It should be noted that there are now vaccines designed to prevent shingles.7 One of these is a live-attenuated vaccine, using the same virus as is used in varicella vaccines. This has been known, albeit rarely, to cause disease. It is contra-indicated in immune-suppressed individuals. A more recent vaccine is a sub-unit vaccine – just using part of the virus, not the whole thing, and therefore not infectious. It includes an “adjuvant” which makes it more immunogenic, and it is at least as effective in preventing shingles as the live-attenuated vaccines.
“It appears that Denmark (the source of this paper) has a zoster vaccination programme to reduce the incidence of shingles, at least since October 2021, as we do in the UK, although the vaccine is recommended for everybody over 50 years of age.8 This is unlikely to affect the findings of this paper, as the people getting shingles will mostly be 60 or more years older than the age at which chickenpox vaccine would be given – so it would take at least this long for the proposed chickenpox vaccination programme to protect them.
“Similarly, it will take some time before we can be certain that the live attenuated vaccines used to prevent chickenpox never cause shingles – although current evidence suggests that it is likely to do so far less frequently than wild virus, if at all. There are some cases of shingles in people who have been vaccinated against chickenpox; but they are uncommon, and at least some of them have been shown to have been caused by wild (not vaccine) virus, suggesting that these individuals had already been infected prior to vaccination, or were infected subsequently despite vaccination; in other words, they were not caused by vaccination. A subunit vaccine, similar to the one recently introduced for shingles, is likely to be even safer, and would have no risk of causing shingles cases.
“The study addresses head on the concerns which are said to have delayed chickenpox vaccination in the UK: the hypothesis (which I like to attribute to Hope-Simpson9) that “exogenous boosting” – exposure to cases of chickenpox – reduces or delays the onset of cases of shingles by naturally boosting immunity to the virus. This concern has been part of the reason for not introducing a UK universal varicella vaccination programme previously.10 More recently the Joint Committee on Vaccination and Immunisation’s (JCVI’s) view on this seems to have shifted.11 paras 55-6, p11 I agree with the authors of the Danish paper that the bulk of the evidence suggests that exogenous boosting has little if any effect in preventing shingles. Furthermore, if it does have any effect, it will be mitigated by a shingles vaccination programme.7 8
“The UK has long varied from many other developed Western countries – particularly North America – in not having a universal vaccination programme for children. (Vaccination of close contacts of people at high risk from chickenpox is recommended.2) I recall a senior official from England’s Department of Health saying (on BBC Radio 4’s “Inside Health” programme), at about the time the Shingles vaccination programme was introduced, that they expected that we would introduce universal chickenpox vaccination in due course.
“This modelling paper from Denmark, a country which is very similar in many ways to the UK (suggesting that its findings are likely generalisable to the UK) finds that universal varicella vaccination is cost-effective; and this supports the idea that the time has come to add it to the UK vaccination schedule.”
‘Universal varicella vaccination in Denmark: Modeling public health impact, age-shift, and cost-effectiveness’ by Burgess C et al. was published in PLOS Public Global Health at 19:00 UK time on Wednesday 5 April.
DOI: https://doi.org/10.1371/journal.pgph.0001743
Declared interests
Dr Peter English is on the editorial board of Vaccines Today: an unpaid, voluntary, position. This comment is made in a personal capacity.