Influenza: prevention and treatment

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

I'm Dhineli Perera, your host for this episode, and it's a pleasure to be speaking to Professor Dominic Dwyer. Dominic is a medical virologist and infectious diseases physician at Westmead Hospital, Sydney. Dominic writes about the current recommendations for influenza vaccine, as well as critical practice points for their use in influenza. Dominic, welcome to the program.

Thank you.

Okay, so, Dominic can you start by giving us some background around the morbidity and mortality induced by influenza in Australia each year?

Yeah, that's a surprisingly complicated question, because not everybody with influenza gets a test, not everybody is sick enough to seek medical advice, be that through general practitioners or at hospitals, and of course, only a small proportion of people are admitted to hospital. But I think one could say that there's about 1500 to 3000 deaths a year. The proportion of people and the number of people admitted to hospital's a little bit difficult to determine, but it's in the range of many tens of thousands each year across the country. It'll vary a bit, depending on the severity of the season, and the strains that are circulating.

Absolutely. So, it's not a small number of patients that we're talking about.

No, no, it's certainly ... No, no, it's a very significant cause of admission to hospital during winter and of course, often what accompanies the admissions to hospital with confirmed influenza are ischaemic heart disease, pneumonia, or with even cerebrovascular disease.

Yeah. Okay. So, what are the influenza subtypes currently in circulation that will be in this year's vaccine? Do these change year to year?

There are two main types of influenza, influenza A and influenza B. There are two subtypes of influenza A, the H1N1 strain and the H3N2 subtype. Within influenza B, there are two what we call lineages, the so-called Victorian lineage and the Yamagata lineage. So, in fact, there's anything from, really, three or four different subtypes, or lineages, of influenza each year.

The proportion of each one of those is what can vary year to year. So, some years, for example in 2009, when we had the big so-called swine flu pandemic, that was an H1N1 strain, and that was by far and away the most dominant strain, and that continued for a couple of years. But, for example, in the last few years, we've seen a lot of the influenza A H3N2 virus circulating, and some years we have a significant amount of influenza B circulating, as well. So, really, it's a mixture each year, and that's what makes it so difficult to predict.

Right. Okay, so, annual vaccination is recommended for everyone over six months who hasn't had previous allergic reaction to the vaccine. Can you tell us who would be considered higher risk of morbidity and mortality, and are all these groups funded under the National Immunisation Program?

Well, influenza can obviously infect everybody, and the groups most at risk are generally the very, very young, so under six months or so of age, and the elderly. Outside of those age groups, the groups that are most affected are those with underlying medical conditions, and that can include a range of respiratory diseases, like chronic obstructive airways disease, cystic fibrosis, people with cardiovascular disease, myocardial disease, and so on, recent infarcts, are also at risk. People with obesity, and very importantly, pregnant women, and that's something that's been observed, particularly in the last decade or so.

Right. And are all these higher risk groups covered by the Immunisation Program, or is it only some groups?

So, the influenza vaccine, of course, is recommended for everybody. It's available free of charge to certain groups, and they're essentially people at risk of significant disease, so that includes pregnancy, people with cardiovascular disease, obesity, and of course, people aged over the age of 65.

Great. And when would you say is the best time to get the vaccination?

Well, generally, influenza's a winter disease, so it usually starts around June, July, but can sometimes start in August or even September, so logically, you need to get vaccinated before the influenza season starts. Now, the difficultly is, you can't quite predict when it's going to start, so usually, vaccination is available from March or April, depending on the production.

Okay, all right, that's good. Good to know. The standard influenza vaccine for children, adults and pregnant women is now a single quadrivalent preparation, although there are a few groups who require a two-dose regimen, that you mention in the article. Can you tell us about the newer high-dose and adjuvanted trivalent vaccines? What are they? Who should get them? And how do prescribers really decide which ones to use?

Yeah, see, the influenza vaccine environment's become a little bit more complicated in the last few years. Basically, the recommendation is for everyone to have the quadrivalent vaccine. That covers the two influenza A viruses, as well as the two influenza B viruses, but it's quite apparent that in older people, and here we use the definition greater than 65 years of age, that the immune response to the vaccine is not as good as in younger people. So, now there's a couple of vaccines that are available that are either higher dose or adjuvanted, in other words, something to promote the immune response to the influenza antigens, and they're the ones that are actually recommended for people aged over 65, because it's a better boost to their immune system.

Right. Okay. So, moving onto antiviral drugs, starting with the neuraminidase inhibitors, your article explains that they need to be started within 48 hours of symptom onset, and are most effective within 24 hours, however there are three options available in this class in Australia. Which should be the option considered, and is there much difference in their benefits?

There are a number of antiviral agents, as you point out. Basically, they're all pretty similar, in that they target the same part of the influenza virus. They have pretty comparable efficacy, or effectiveness, in established influenza. They are given in different ways. So, for example, the most commonly used one is oseltamivir, and that's given as a tablet twice a day, for five days. There is an inhaled neuraminidase inhibitor called zanamivir, and that has advantages, because you only have to give a number of doses of that, but people do have ... may have difficulty in taking an inhaled agent. So, in fact, the way the market has gone over the last few years, it's the oseltamivir tablets that are the most widely used.

Mm-hmm (affirmative). And I think it mentions an intravenous option, as well?

There are some intravenous preparations that are available. Of course, they're most likely to be used in patients that are admitted to hospital, so in the intensive care environment, where you have an intubated patient, then obviously, an intravenous preparation offers significant advantage. One of the difficulties, of course, is that the trials show that you need to give these drugs within 48 hours to have the best effect. The trouble is, it takes a while for people to perhaps visit their GP and be admitted to the hospital through the ED. Look, there are variations in how people prescribe it, but I think in community patients who are unlikely to require admission to hospital, you could probably say that, beyond 48 hours, the drugs don't offer terribly much advantage.

So, when should antiviral resistance be suspected?

Basically, resistance is uncommon, which is great, so that, for the average reasonably healthy person, highly unlikely to develop resistance. Yes, it has been described, but it's rare. The problem where resistance can emerge is in people who are profoundly immunosuppressed in hospital, so, for example, they're a transplant recipient, and in those people, they tend to shed virus for longer, and in higher amounts, so the antiviral drugs can lose their effectiveness because of resistance.

Okay. I was actually surprised to see that amantadine was the one adamantane available in Australia for influenza prophylaxis. Most of us would be more familiar with its use in Parkinson's. When should prescribers consider this option, if at all?

Oh, look, I don't think these drugs are worth using anymore. Amantadine was a drug that was used for influenza A infections, it doesn't work against influenza B, in decades past. The trouble is, first of all, the drug has very significant side effects, you know, about 30% of people have significant side effects from amantadine. And resistance develops really quickly, much more quickly than with the neuraminidase inhibitors. So, to be honest, there's no value in using amantadine in routine clinical practice.

Okay, well that's good. That rules that out.

Mm-hmm (affirmative).

So, with regards to antiviral prophylaxis, your article clearly states that there is ... it's not really an alternative to vaccination. Individuals do remain susceptible after the course is completed, and extensive use could encourage resistance, but it does have its place. So, could you tell us a bit more about who should be prescribed prophylaxis, when, and for how long?

It's been shown that antiviral prophylaxis, say, for example, with ... well, with any of the neuraminidase inhibitors, does reduce the likelihood of acquiring influenza. I think it's reasonable that, if you have a household member who has laboratory-confirmed flu, if there are other members of the household who, for example, are particularly immunosuppressed, or who may be elderly, or at risk of influenza, in that situation, you could warrant giving prophylaxis. The other option, of course, is advise them to take a treatment course, should they get sick. The other area you might use prophylaxis is in what we call closed environments, where there's lots of people together, so, for example, in a nursing home, or even in a hospital ward. If there's an outbreak, then giving prophylaxis to the others reduces the likelihood of them getting influenza.

Okay. Fantastic. Well, that's, unfortunately, all the time we've got for this episode. Thanks so much for joining us today, Dominic.

That's a pleasure.

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The views of the hosts and guests on the podcast are their own and may not represent Australian Prescriber or NPS MedicineWise. I'm Dhineli Perera, and thanks for joining us on the Australian Prescriber Podcast.