• 24 Mar 2020
  • 16 min
  • 24 Mar 2020
  • 16 min

David Liew interviews Kristine Macartney about herpes zoster vaccination. What is it, who’s it for, and how effective is it? Read the full article in Australian Prescriber.


Welcome to the Australian Prescriber Podcast. Australian Prescriber, independent, peer-reviewed and free.

Shingles, even the word evokes a little fear and it's no surprise given the pain and blistering that shingles, herpes zoster, can cause, not to mention the postherpetic neuralgia that can be an issue long after the rash is gone. Shingles is common as patients get older or the patient is on immunosuppression. But, where do we stand in Australia on vaccinating against it?

I'm David Liew, your host for today. I'm joined by an expert in this space, Professor Kristine Macartney who is a director of the National Centre for Immunisation Research and Surveillance and infectious diseases physician at Westmead in Sydney. She and her colleagues have detailed out the herpes zoster vaccination state of play in Australia in the February 2020 edition of Australian Prescriber. So, it's a pleasure to have her on the podcast today. Kristine, welcome to the program.

Thank you very much, David, and it's a pleasure to be here.

Now let's talk about shingles, about herpes zoster itself, to start with. How does it happen and why does it matter to the point that we would make this kind of fuss about vaccinating against it?

Well, as you mentioned, shingles is caused by the varicella zoster virus, which has one of the best names because it describes varicella, which is also known as chicken pox, which is the clinical syndrome that people get when they're first infected with that virus, usually in childhood. So most people in Australia, most adults have had chicken pox before, even if they can't remember it. And then the virus actually becomes latent or dormant in our dorsal root ganglia, so the nerve roots of the spinal column, and does reactivate in many people as we either age or as you talked about in the context of immunosuppression either from a medical condition or from medical therapy.

I mean, I can imagine it's the kind of thing as well that while it's not, well, it's debilitating for an individual, the community impact is quite substantial that it really does mean a cost to this country and its health system.

Absolutely. And that's been shown in a number of studies across the globe actually. The cost, not just at that individual level with that impact on activities of daily living or overall wellbeing, but from the health economics point of view. This is a really serious condition.

It's important to note here that every vaccine that does get onto the National Immunisation Program Schedule has to be evaluated very critically for cost effectiveness. And for this vaccine, the shingles vaccine, which is called Zostavax, a live attenuated vaccine, it was actually evaluated a couple of times and the age group at which it's targeted, so 70 to 79 year olds, turns out to be the best age group to vaccinate from a cost-effectiveness point of view.

Why is that the case? Why in particular that decade and why are these patients at greater risk?

So, the vaccine is licensed from the age of 50 years. It's probably important to step back a little bit and just remind everybody that it is a live attenuated vaccine. So it acts to boost T-cell immunity to the virus.

The incidence of the disease really rapidly climbs from 60 years of age, so that's shingles itself, but also postherpetic neuralgia, the nasty long-term nerve pain that can occur in some people, and that really then kicks up even more as you head into your 70s and into your 80s.

Now, it was a complex sort of modelling exercise to really work out where that sweet spot was, but the vaccine is slightly less efficacious as you age, but it still seems to retain its impact against postherpetic neuralgia. So when all of those things are factored in together, the incidence of the disease, the effectiveness or efficacy of the vaccine, it turned out that 70 was the best age from which to have the vaccine program. And there is this short-term catch-up program offering free vaccine to everyone 71 to 79 years of age.

Really important for your listeners to be aware that if you have a patient who wasn't vaccinated at 70 or is now 70 to 71 to 79 that they're still eligible for the free vaccine and should try and get it soon.

As a taxpayer, I'm really glad to hear that we're targeting this at the place where we've got the biggest bang for our buck. Can you tell me a little bit about how efficacy goes on in the years after vaccination?

In the age group that we're talking about, the vaccine is about 50% protective against herpes zoster. So, that's not 100%, we'd like that to be greater, but that's still got a big impact both at the individual level and the population level. In the first few years, that efficacy against the postherpetic neuralgia is around 66%, so higher in fact, than against getting the shingles itself.

The vaccine then does wane in effectiveness over time. So, by around five to 10 years after vaccination, we're seeing much lower rates of protection. So, more around 20% to 30% rates of protection.

With respect to effectiveness, we're not currently recommending a second or booster dose of vaccination. That's something that is always being monitored and considered. And there’s definitely ongoing studies in that area. Likewise, we're not discouraging people who are already 80 or indeed over 80 against being vaccinated. They certainly can receive the vaccine. They just may get somewhat less protection.

Actually, let me ask you a related question. What do we do when someone's had an episode of shingles? Do we vaccinate them after that and how long might we wait? What kind of dynamic do we look at there?

Having an episode of shingles is very unpleasant, but it does give you an immune boost to the virus. So it's not necessary to be vaccinated right away. We advise to wait for somewhere between one to three years after the shingles episode.

We've got this vaccine, which we're targeting to the people who it's going to have the greatest impact in, although others certainly can have it. We know that it doesn't just stop the infection itself, but it stops the debilitating pain that can follow it. What about the other side of the coin, what about safety? We've been talking about a live vaccine here. Is this something that we need to be worried about or what have the safety data shown us so far?

Overall, the vaccine has had really encouraging good safety profile both in pre-licensure clinical studies in which there were a number including the Shingles Prevention Study, which enrolled 40,000 adults over the age of 60 years. And postmarket surveillance has also shown a very good safety profile.

Around half of the patients who receive the vaccine get a mild reaction at the injection sites. So, that's just short lived. It goes away without any specific treatment. Generally, on the scale of things, say compared to the pneumococcal vaccine, it's very well tolerated.

That being said, the challenge from a safety perspective for this live attenuated vaccine is that it is contraindicated in patients who are significantly immunocompromised. Now, patients who have chronic conditions can be vaccinated, so many of the listeners will know that in their older population, the prevalence of cardiovascular disease, diabetes, various other conditions, those patients can be vaccinated. But, it is necessary for immunisation providers to screen their patients prior to vaccination and be sure that they're not on an immunosuppressive medication or have a significantly immunocompromising medical condition.

Okay. Obviously, as a rheumatologist, I do give medications like methotrexate and azathioprine. What about my rheumatoid arthritis patients who are on methotrexate 20 mg weekly on a standard rheumatoid arthritis dose, what should I do about Zostavax in that situation?

There is a lot of really detailed information in the Australian Immunisation Handbook. If your patient on a very low dose methotrexate doesn't have any other significant immunocompromising conditions, if they're not on any other DMARDs, if they're otherwise well, they haven't been on say, a recent high-dose course of corticosteroids or even low-dose course of corticosteroids over a long period of time, they would be safe to be vaccinated. So in general, patients on low-dose azathioprine, mercaptopurine and methotrexate, patients on denosumab for example, these patients are all fine to be vaccinated in the absence of any other immunocompromising conditions.

I guess this is a space where we're constantly collecting data as well. I mean, the surveillance system around vaccinations in this country is fairly comprehensive I would've thought.

Look, it is. But I think, again, for the primary care population in particular, this is a new vaccine in the sense that we've never used a live attenuated vaccine in older people before. So, unlike influenza or pneumococcal vaccine, which are not live, they're killed or component vaccines, this vaccine we do have to take those extra steps. We have to screen and then importantly counsel patients about the potential of adverse effects. So, it's important to tell patients that if they were to experience a rash, particularly a pustular-like rash after vaccination, come back and have a review.

But importantly, we have had reports of the occasional patient having a generalised vesicular-type rash in the couple of weeks after vaccination, sometimes in the context of a patient who has been on a degree of immunosuppression. So, if clinicians are making a decision with their patient to go ahead and vaccinate in the context of some mild immunosuppression, just to be sure to have that follow-up to see how that patient is doing.

I guess the other point in this space is the fact that in Australia we do have registered the recombinant subunit zoster vaccine, the non-live vaccine. Can you tell me a bit about where we stand with that?

Absolutely, and that vaccine is called SHINGRIX. There were two New England Journal publications on this vaccine, which shows really very high efficacy in older people. So, even in the 70 year age group that we're talking about, 90% plus efficacy against herpes zoster and almost no cases of postherpetic neuralgia. So, that vaccine holds a lot of promise and because it isn't live can potentially be used in quite immunocompromised patients.

Unfortunately, although that vaccine was licensed in Australia a few years ago, there are global supply issues, but at this stage it isn't something that Australian patients can access, unfortunately.

Right. Well, in the meantime, we've still got Zostavax. It's on the National Immunisation Program. Tell me about how this has been going in Australia. We've had it for a few years now. Where are we at with that at the moment?

Well, we did see a lot of enthusiasm around the program when it commenced in November 2016, so we're talking now a little after three years into the program. We saw a lot of vaccine distributed and anecdotally, a very strong demand at the general practice level.

There were some initial teething problems with the program and indeed an evaluation of the first 18 months or so of the program from my centre, the National Centre for Immunisation Research and Surveillance, showed that there were some challenges and difficulties applying the age criteria, a slightly different criteria for the other vaccines we use in older people. Just a few challenges in supply early on. But, the need to become familiar with screening patients and the contraindications.

There was a lot of vaccine delivered, but unfortunately what we've seen reflected in the Australian Immunisation Register is recorded uptake or coverage of the vaccine of only around 30% or so. So, that's in the catch-up cohort. And then a little bit lower in the annual cohort of 70 year olds. So unfortunately, not as much coverage as we would like to have seen recorded.

The question for us then in conducting this evaluation was, why does coverage appear to be lower than we'd hoped? It's probably due to a few factors. We think that the recorded coverage in the Australian Immunisation Register is underestimated probably due to some factors at the general practice level in terms of perhaps recording how the vaccine is entered into the practice software, how that data is then transmitted up to the Australian Immunisation Register, that the expansion of the register to include adults is new and some GPs may not have had their practices fully linked up. Perhaps, some of the general practices that are giving this vaccine are not realising that the register has been expanded.

Really. All right, so I think the final question I've got on this front is, what can we do about trying to improve that uptake?

Look, there are many ways to improve immunisation coverage in general and also for this particular vaccine. Certainly at the patient level, it's important to provide awareness of the disease, you're discussing it with them, that you're offering the vaccine. Providers can implement a number of measures to ensure that they're making it easy to vaccinate their patients, so they can do recall reminders. They can particularly focus on catching up patients when other vaccines are being delivered such as during the influenza vaccination season. It's perfectly okay to give this vaccine with influenza vaccine, with pneumococcal vaccine.

And then at the broader public health level, obviously feeding back on the data, ensuring that general practitioners and nurses are being educated around the importance of being vaccinated. So, many things I think across the board that can be done and hopefully we'll have this preventative measure offered to all the targeted age group.

Well, let's hope that those things have the impact that we think we all really want. Kristine, thank you so much for joining us on the program today.

Thank you very much, David. It's been a pleasure.


The views of the guests and the hosts on this podcast are their own and may not represent NPS MedicineWise or Australia Prescriber. I'm David Liew. And once again, it's been a pleasure joining you on the Australian Prescriber Podcast.