Introduction

Speakers will present the recommendations from the National Advisory Committee on Immunization’s (NACI) Seasonal Influenza Vaccine Statement 2019-2020, and the Association of Medical Microbiology and Infectious Disease (AMMI) Canada’s Guidance for Practitioners on the Use of Antiviral Drugs for Influenza.

Published: 2019

Subject Area(s):

Author(s):

Influenza constantly evolves. Learn about the 2019-2020 recommendations for prevention and treatment of seasonal influenza.

Speakers:
Dr. Ian Gemmill and Dr. Gerald Evans, Infectious disease experts

Speakers presented the recommendations from the National Advisory Committee on Immunization’s
(NACI) Seasonal Influenza Vaccine Statement 2019-2020, and the Association of Medical Microbiology and
Infectious Disease (AMMI) Canada’s Guidance for Practitioners on the Use of Antiviral Drugs for Influenza.

This webcast provides frontline healthcare practitioners and public health vaccine providers with:
• An overview of the epidemiology for recent influenza seasons
• The information they need to support their practice during the
2019-2020 influenza season
• An opportunity to pose questions to infectious disease experts

A copy of this webinar is available upon request. Please contact NCCID Project Manager Aleksandra Wierzbowski to learn more, or get in touch with our Centre via our general email account.

Transcript

Aleksandra:

Hello everyone. My name is Aleksandra Wierzbowski. I am a Project Manager at National Collaborating Centre for Infectious Diseases. I welcome you to today’s Webinar, Guidance on Seasonal Influenza 2019-2020 NACI and AMMI Canada recommendations.

You should be able to hear me well through your computer speakers, or computer headphones. Please turn up the volume on your computer audio. If you find the computer audio is not optimal, please join the Webinar using the Teleconference line provided on your screen. An email address on your screen is provided. In case of other technical difficulties please email us and we will do our best to assist you. Alternatively, you can also alert us using a Chat Box. Today’s Webinar will be recorded and available within the next week.

The objective of this Webinar is to provide an overview of the burden of influenza, the current National Advisory Committee on Immunization (NACI) and Association of Medical Microbiology and Infectious Disease (AMMI) Canada recommendations on the prevention and treatment of influenza, as well as to outline key messages and available resources for 2019-2020 influenza season.

Following the 45 minutes presentation, we will have time for your questions. For those of you who can stay, we will continue with questions past the hour. We encourage you to post your questions in writing in the Chat Box.

Our speakers will address some of the questions in writing as we move along. NCCID is one of the six National Collaborating Centres for Public Health, each focusing on different area of Public Health. NCCID is funded by Public Health Agency of Canada to provide knowledge translation, helping public health practitioners find, understand and use infectious disease research and evidence.

It is now my pleasure to introduce our speakers. Dr. Gerald Evans is the Chair of the Division of Infectious Diseases and a Professor in the Department of Medicine, Biomedical and Molecular Sciences, and Pathology and Molecular Medicine at Queens University. He is an attending Infectious Disease Physician at the Kingston Health Sciences Centre and Providence Care Hospital in Kingston, Ontario. Dr. Evans has been a Medical Director for Infection Prevention and Control at these two facilities since 2011. He is a member of AMMI Canada Influenza Working Group and a past President from 2009 to 2011.

Dr. Ian Gemmill has 38 years of experience in public health in Ontario. He is an Associate Professor in the Department of Family Medicine and Public Health Sciences at Queens University. He is a Fellow of the Royal College of Physicians and Surgeons of Canada in Public Health and Preventive Medicine, an Honorary Member of Canadian Pediatric Society, an Honorary Life Member of Canadian Public Health Association and a Fellow of College of Family Physicians of Canada. He is the past Chair of NACI and is currently the Chair of NACI’s Working Group on Influenza vaccine.

Without further ado, I welcome Dr. Evans, to begin the presentation with the burden of influenza in Canada.

Dr. Evans:

Thank you very much Aleksandra. So we are going to start off with a sort of brief overview of the current burden of seasonal influenza in Canada, with a little bit of a reminder about what influenza infection and illness looks like. We are just waiting for the slides to come up.

So I am always reminded – and people certainly know that influenza is a relatively significant and severe infection in most people. And the illness itself is severe enough that it leads to substantial absences from both school and work for a large number of Canadians every year.

The illness itself can last upwards of a week, versus what you would expect with a common cold, which might be as short as three or four days. It’s estimated every year there are over, you know, 12-thousand hospitalizations and certainly a substantial number of deaths, which can be attributable to influenza. Although, some of those are not necessarily due to the infection itself, but rather complications that can arise, particularly in high risk groups, in which illness from influenza can substantially exacerbate underlying conditions.

There are a lot of different characteristics that sort of impact on the risk of acquiring influenza. As well, there are factors that are important in the severity of influenza when you get it.

In this slide you can see there are a number of groups that – and specifically we recognize that complications as a result of influenza infection can be substantial. And those include pregnant women, children under the age of five, adults over 65 years of age, adults and children who suffer from chronic health conditions, including not just cardiopulmonary disease, but other diseases like diabetes.

Those that reside in nursing homes and chronic care facilities – also often times because of underlying health conditions – can have problems. And for a reason that’s still not well understood and that we are currently working on, it is recognized around the world that Indigenous people have a much higher rate of serious, or severe influenza.

The conditions that are associated with high risk for problems, once influenza is acquired, include cardiopulmonary diseases, diabetes as I mentioned, those individuals who are immunocompromised due to treatment for underlying problems, such as cancer and nowadays of course, immunotherapies directed for patients with rheumatological, gastroenterological and some dermatological conditions.

Those that suffer from end-stage renal disease, those that are anemic, or have hemoglobinopathies are also deemed to have more serious complications.

And we recognized after the 2009 flu pandemic, that those with neurologic or neurodevelopmental problems also had an issue with regards to the development of severe, or complicated influenza.

And then lastly, those with significant obesity, those that have a BMI of over 40 have clearly been noted to have a much higher likelihood of developing severe problems, once influenza is acquired.

So again looking at age groups, one of the interesting things is that there is some difference in terms of how and which influenza viruses tend to produce a higher burden of disease. For those over the age of 65, in which other illnesses can certainly be present – comorbid conditions – they can be disproportionately affected by years when the dominant influenza strain is an H3N2 one.

Conversely, children actually have a higher disease burden when it comes to influenza B infections. And certainly as I mentioned, those under the age of five can have a substantial greater risk for severe influenza-related complications.

This is a little graph which shows the last five years of influenza seasonal activity in Canada. And what you can see here, is last year we had the peak of the influenza season occurring sort of into the late part of February, early March. Although the onset of disease and the recognition of influenza rising in Canada, occurred as early as – the early part of January.

It was a year with a fairly long tail towards the end and that was – as you’ll see in a second – due to the emergence of a different influenza A stream – strain – than one that predominated early in the year. And you can see comparatively, some of the other years actually had earlier onsets of peak influenza activity.

This is a breakdown not of last year, but of the two – of the four previous years to that. And as you can see, each year the kind of influenza type either A or B will change and vary. And those are related often times to population susceptibility and may relate to previous year vaccination and/or the emergence of an antigenically drifting strain for which population immunity doesn’t occur.

And in 2017-2018 you can see with the blue pie part of the graph, influenza B actually accounted for almost half of the strains that were seen in that seasonal influenza.

This is last year, 2018-2019, and sort of expanded over the year. You can see that again with influenza, this is laboratory confirmed cases, so it’s different than our sentinel clinical surveillance, to some extent. These were strains that were found, confirmed positive and then later typed.

And what we saw – and you can see with the darker red bars – is that early on in the season, it appeared to be mostly H1N1 influenza A, very similar to the Pandemic ’09 strain, which was part of our vaccine. And then that seemed to die off a bit and then we had the emergence of more H3N2 activity, following sort of towards the end of February and going out fairly far, almost really to the end of the season, as we normally see.

Last year was not a big influenza B season, but you could see in very small bar amounts that there was some influenza B that started to emerge later in last year’s season. So last year was a predominantly A season with H1N1 early in the season and H3N2 later in the season.

This is surveillance data related to visits to healthcare professionals with influenza-like illness. So these were people who presented with ILI that were just recorded as ILI, may or may not have been influenza, although we recognize – as you can see from this peak which corresponds with the laboratory confirmed data – that most of those were in fact, influenza illnesses.

And you can comparatively look at the previous five year average from 2013 to 2018 and then the solid bar you can see last year’s visits. And it followed a fairly predictable pattern that we would see, other than this sort of extension out to what appeared to be a little bit longer season, although I can say that as one of the Northern Hemisphere countries, it was not as prolonged as we saw in for instance, the country that is our Southern neighbour.

If you look at hospitalizations, and these are breaking it down – this is not last year’s data, but the three previous years to that – you can see that in some seasons there is a tendency towards more hospitalizations in children. And none of these, however, were a B predominance, in which you would expect to see that. And what we see is when H3N2 tends to dominate a lot, or if there is poor immunization of an older population, then the other burden is carried by those over the age of 65 when it comes to hospitalizations for complications and/or severe Influenza.

So I want to take the next three slides to quickly talk about the Southern Hemisphere, because it has got a lot of press -about the concerns. And that concern basically came out as a result of Australia reporting what seemed to be a very early onset to their seasonal influenza, with large numbers. And this caused a great deal of concern amongst many people, as to whether or not this might predict what is going to happen up here in the Northern Hemisphere.

So their season typically starts in June, but they began to actually see an increase that preceded their season and in fact when the season hit, there were already fairly high levels.

It is now apparent and they did publish data on this that showed that the reason for this was actually kind of unique – and it’s uniquely related to the geographical climate of Australia. For those of you who are familiar, or maybe not so familiar with Australia, the northern part of the country is actually tropical and in fact the very northern tips, equatorial.

In tropical and equatorial regions of the world, influenza doesn’t have a season. It tends to be transmitted around in low levels all year round. Whereas in temperate climates, which is southern Australia and of course, Canada, United States and Northern Europe, we tend to see seasonal influenza which then disappears during the inter-seasonal period.

So what actually happened in Australia was there was a fair bit more than usual inter-seasonal influenza, circulating in the northern part of the country and in particular, the largest City in the north of Australia, called Darwin.

And so patients with that inter-seasonal influenza, who had travelled around Australia, were actually carrying it to the other areas. So there was an increased amount of influenza all-in-all in Australia and it appeared to be this very early onset to the seasonal strain.

So the Australians believed that this was unique to them and was related to this unique problem of their geography and the high levels of inter-seasonal influenza. And in fact that’s born out, because if you look at some of the data from other countries – and I’ll just show you the Australian graph which shows this large increase and apparently reported numbers of laboratory confirmed Influenza – that was not seen in New Zealand. It was not seen in the temperate regions of South America, Argentina, and Chile and was not seen in South Africa.

So they’re probably correct in that this was a uniquely Australian issue. And so I’m not sure that it’s going to be predictive of what we’re going to see here in the Northern Hemisphere.

And then lastly I’ll just show you this graph, which is the number of hospitalizations in Australia with the dark – or the bright red line showing the number of hospitalizations. And what you can actually see is although there was an early onset of influenza with hospitalizations, as the season wore on, it actually returned to somewhat normal levels.

And in fact the data that we’ve seen now from Australia suggests that overall, despite an early onset to the influenza season with larger numbers, it panned out to be a typical season, in terms of the numbers of hospitalizations and some attributable morbidity and mortality.

So I think the Southern Hemisphere blip in Australia, probably is unique to them and at this point, I’m not quite sure that we’re going to see the same thing happening here. I will remind everyone there is not a single part of Canada that would be considered equatorial, or tropical.

So on that note, I am going to turn it over to my colleague, Dr. Gemmill, who’s going to talk to you about vaccine use and vaccine availability for the upcoming season.

Dr. Gemmill:

Thanks very much Gerald. I hope that people can hear me. I want to first thank the National Collaborating Centre for Infectious Disease and the Public Health Agency of Canada, for the opportunity to present the recommendations from the National Advisory Committee on Immunization, for the use of influenza vaccine for 2019-2020.

I’m going to be presenting the main changes in the annual statement from last year and just a reminder that this statement can be found on the website of the Public Health Agency of Canada. And please note as well that the recommendations that NACI has made, may differ from the vaccines offered in provincial programs and that LAIV will not be marketed in Canada by the manufacturer this year. I will make a bit more comment about that at a later time.

I also want to remind people as well, if you haven’t already received the slides, they will be available. And there’s several slides here. They’re really just for your reference so you can use it as you need it through the influenza season.

So just to remind you that NACI is an external advisory body to the Public Health Agency of Canada that makes recommendations on the optimal use of vaccine to protect Canadians. And it’s been providing rigorous expert and evidence-based advice on vaccines for over 50 years. It comprises experts in health professions and professional associations that are listed in this slide here, from across Canada.

So carrying on – NACI makes recommendations for vaccination of individuals and more broadly for vaccine programs. Recommendations on the use of vaccines are made based on NACI’s evidence-based process and every year they issue a statement on seasonal influenza vaccine that informs healthcare providers on the optimal use of influenza vaccines, based on the most up-to-date data available. And just to remind you as well that the statement on influenza and the chapter in the Canadian Immunization Guide, are one and the same.

So this autumn, NACI has officially expanded their mandate to include consideration of key programmatic factors – in addition to the scientific factors – in decision-making for vaccine programs. These criteria are based on the model by Erickson and De Wals that is referenced at the bottom of the slide there for you.

In past years, NACI has focused on the four criteria in the bar on the left, including burden of disease, characteristics of the vaccine, such as safety and immunogenicity, immunization strategies and research questions.

This year many of the other criteria of the Erickson and De Wals framework have been considered and are listed on the right side of this bar. So things like feasibility, acceptability and especially cost effectiveness. Some criteria, of course are in the domain of the provinces and territories and those are the ones at the top, political, legal and so on.

So what is new for 2019-2020 – NACI’s Influenza Working Group has undertaken a number of projects over the last year. One such project was to investigate in the literature, whether there was any evidence that split virus vaccines, provided better protection and subunit vaccines – a question that may be of considerable interest when deciding which of the many vaccines are available to provide in a program, or to give to specific patients.

And just to remind you that the split virus vaccines contain all different parts of the virus, while the subunit vaccines contain only purified surface proteins – that is hemagglutinin and neuraminidase. NACI has concluded that there was not enough evidence on the effectiveness or immunogenicity to support specific recommendations on the differential use of these vaccines. And concluded therefore, that there is not enough evidence to make a preferential recommendation on the use of these two different types of vaccines.

Next with the proliferation of the types of influenza vaccines, we’ve had to revise the abbreviations used for clarity and to avoid errors. So for example, there are different kinds of trivalent vaccines, such as standard dose, high dose and adjuvanted.

To distinguish amongst all of these formulations, we have adopted IIV3 – that is inactivated influenza vaccine trivalent instead of TIV, which then allows qualifications of the various vaccines and I’ll explain as we go through this.

HD trivalent – that’s high dose – is referred to as IIV3-HD and adjuvanted as IIV3-Adj to distinguish amongst them. The same process was used for IIV4, which was formerly known as QIV.

This system allows us to expand the inventory of abbreviations in the future as new formulations are developed, such as cell-based, plant-based and recombinant vaccines, which will be coming to you in future influenza seasons, and also aligns largely with terminology used by others, such as the Centre for Disease Control in Atlanta.

So as many of you know, the selection for the strains of influenza vaccine for the Northern Hemisphere is made by the Strategic Advisory Group of Experts (SAGE) in February of each year. There are changes for both the H1N1 components to A/Brisbane and for the H3N2 to A/Kansas. This latter strain circulated more in the U.S.A. than other countries and was the reason for the delay in making the recommendation by SAGE until March of this year.

And this delay is also one of the reasons for the delay that some of you may be experiencing in the availability of influenza vaccine this year. The IIV3 pre-formulation contain B/Colorado from the Victoria lineage that Dr. Evans has mentioned and the IIV4 formulation adds an addition to the B/Colorado, the B/Phuket from the Yamagata formulation.

Here for your reference is a list of all of the vaccines that will be available in Canada for this influenza season. There are four IIV4 vaccines and the age groups for which they’re licensed, I listed there for you. There are two IIV3 vaccines, both licensed for six months of age and older. And in addition to the regular influenza vaccines, there are specialized influenza vaccines designed to enhance immunogenicity in specific age groups, such as the high dose and perhaps the adjuvanted vaccine for adults, 65 years of age and older.

So there are two adjuvanted IIV3 vaccines, one formulation for older adults and one for children age six to 23 months. And there is one high dose IIV3 vaccine for use in older adults. And as I said previously, please note that not all products will be made available in all jurisdictions and the availability of some products may be limited, the decision to include specific influenza vaccines as a part of a publically funded provincial and territorial program, will depend on a number of factors, including the cost effectiveness analysis that the provinces and territories may undertake.

I also want to mention that FluMist, the quadrivalent LAIV authorized for use in Canada will not be available this year. AstraZeneca Canada, the Canadian supplier of FluMist has decided not to market this vaccine in Canada and has cited production challenges with this year’s vaccine that has led to a low global supply.

The decision to market a vaccine in Canada rests entirely of course, with the [vaccine] manufacturer and this vaccine will be used in the U.K. and available in the U.S.A. as I understand it. So you may be hearing something about it from patients who receive their vaccine there. And there’s more about the vaccine shortage on Drugshortages.ca.

So who should receive influenza vaccine? I’m not going to read this entire list, because you’ve actually seen this many times I’m sure. The people with influenza-related complications or hospitalizations and the four different categories are listed there for you that you’ve already heard from Dr. Evans – people capable of transmitting to those at high risk, essential community services, so that we don’t lose our skilled workers in these fields, because they’re ill, and then a special category of poultry workers to avoid the theoretical possibility of some kind of a combination with an avian influenza that may lead to possibly a dangerous combination.

So those are the general groups. Then in terms of the specific groups, you’ve seen this list many times before and Dr. Evans has listed it when talking about the high risk groups for influenza, so it is provided there for your reference.

With regard to older adults, because of immunosenescence, this population are at a greater risk for serious influenza-related complications. And while the severity of influenza varies from season to season, the burden of severe influenza disease including hospitalization and death, is greatest in this population.

And in particular influenza H3N2, disproportionately affects older adults. So this is one of the reasons why we have them on our list. And even in the pandemic of 2009 when there were fewer cases of this pandemic strain in older people, those who did become ill, became quite ill.

So they’ve been on the list for decades and the choice of this vaccine, however, has caused a little bit of confusion. NACI has not identified that adjuvanted vaccine provides better protection than standard vaccine, but you may see out there that some jurisdictions such as the U.K. have made it preferential.

The high dose vaccine is thought to provide better protection, so NACI has made this as a recommendation for older adults. But again, some provinces have made their own assessment of a value and cost-effectiveness of these three choices, so the specific vaccine offered to older adults will vary from province-to-province.

Children younger than five years of age, particularly those younger than two years of age are at increased risk of influenza associated complications, compared to older children and especially for those under the age of two. About a third of the hospitalizations are reported by the IMPACT – Canadian Immunization Monitoring Program ACTive.

And according to IMPACT, since the 2014/15 season, up to eight influenza-related pediatric deaths have been reported each season. So although the deaths are rare, some children do die from influenza every year in Canada.

One other point is that the vaccine is less immunogenic in infants less than six months of age and does not give sufficient protection and that’s why it’s not used in that age group. It’s not because the vaccine is harmful in that age group.

Influenza in pregnancy is worse for both the mother and the neonate. Although the absolute risk is not great, the relative risk is important. The changes to the immune system in the body during pregnancy, make pregnant women more vulnerable to developing complications. The vulnerability to influenza infection does increase with the age of the gestation, so therefore the third trimester has a – there is a greater risk than the second trimester.

And, in addition, influenza infection during pregnancy, increases the adverse neonatal outcome such as low birth weight. We used to recommend avoiding vaccines, including influenza vaccine in pregnancy, unless there was a specific risk to the mother or infant. We now have the evidence to show that there is risk. So the provisions of vaccine in pregnancy, it’s not only safe, but it is also recommended, unless there is a specific contraindication.

In addition to protecting the pregnant women, as I mentioned it also protects the infant. Pregnant mothers who are vaccinated against influenza will pass on antibodies that will help to protect their newborns against influenza. Antibodies provide the newborn – via breast milk from vaccinated mothers – can provide some protection and, of course, if the mother does not contract influenza, then she will not be able to transmit it to her infant.

Now a word or two about the schedule. Just to give you a couple of reminders that the reason why we have annual immunization against influenza [is] that our body’s immune system from vaccination diminishes within that timeframe. And as most of you know, the circulating influenza viruses change frequently, necessitating annual changes in vaccine strains.

And as a reminder, any child under nine years of age should receive two doses, a priming dose and a second dose. The two doses should be in the same season theoretically, but needn’t be if one dose has already been given in a previous season. And it can be given with any inactivated vaccine or LAIV.

For your reference, here are the specific vaccines recommended for various age groups. For children, NACI recommends quadrivalent over trivalent. As Dr. Evans has mentioned, the greater burden of influenza being this group and we want to make sure that if there’s a mismatch between the Victoria and the Yamagata that we have both in there.

For those 65 years of age and older, due to an increased burden, as I’ve already mentioned and good evidence of better efficacy of the IIV3 high dose, compared to standard dose, NACI recommends that the high dose IIV3 should be used over the standard dose for individuals.

And again for your reference is the chart of the doses of the various influenza vaccines for the various age groups and we’ve already discussed the two doses for children less than age nine.

So all influenza vaccines are contraindicated for people who have had an anaphylactic reaction to a previous dose of influenza vaccine. Egg allergy, however is not a contraindication any longer for influenza vaccine. Several seasons of post-marketing safety surveillance in Canada and studies challenging persons with an allergy to egg have shown that egg allergy does not appear to be associated with a greater proportion of a spontaneous reports of anaphylaxis, allergic, or any allergic-type adverse events following immunization. And that makes sense in a way, because the dosage of egg protein in influenza vaccine is so vanishingly low that it is unlikely that it would ever trigger an allergic reaction.

And it’s really important to emphasize the safety of the influenza vaccine, because even more than effectiveness, people want to know that the vaccines are safe. Injection site reactions are the most common and are generally mild and transient. Serious adverse events are rare following influenza vaccination. And in most cases, the data are insufficient to determine a causal association and very important to be able to – to share with patients that the safety of influenza vaccine is continuously monitored by the Canadian Adverse Events Following Immunization Surveillance System. So the bottom line, influenza is a safe vaccine.

And if you look at this in context, if we look at for example, the risk of Guillain-Barré Syndrome (GBS) following influenza vaccine, we know it’s approximately one additional case per one million doses of vaccine. But the analysis by Jeff Kwong and his colleagues, showed that the risk of GBS following influenza illness, is ten times greater.

So the conclusion is that GBS following influenza illness is a greater risk than GBS following influenza vaccine. What can healthcare providers do? Well as a healthcare provider, patients trust your recommendations the most. You are key drivers for vaccine uptake.

And so what is some of the message we can give to people? First of all, healthcare providers can do their part by getting the influenza vaccine themselves and for helping to prevent transmitting influenza to patients, using every opportunity to vaccinate people at risk, even after the influenza activity has been documented in the community and discuss the risks and benefits of the vaccine with patients, as well as the risk of not being vaccinated.

Just a word or two about influenza effectiveness. Vaccine effectiveness (VE) varies according to several factors. First of all, how well the vaccine strains match with circulating influenza viruses, the type and subtype of circulating viruses, the health and age of the individual receiving the vaccine, unexpected inter-seasonal and intra-seasonal drift and mutations that are acquired during the production. We know this happens during production, or using egg-based vaccines.

Effectiveness of influenza vaccine has been a growing concern over the last several years with finding sometimes, far lower than we had assessed two or three decades ago. It is therefore helpful to look at the VE to understand that a vaccine can still protect people, even if the vaccine effectiveness is not 100%.

And it’s very hard to assess this VE. We’re very grateful to the people in Canada who have taken on this responsibility for us and to provide this data for us every year.

So just to give you an example, let’s suppose influenza has an average attack rate of say 10%, this means that in a group of unvaccinated individuals – and we’ll just ignore herd immunity for the moment, ten will be infected with influenza.

If the vaccine were 100% effective and all 100 people were vaccinated, then we would avoid – or prevent ten cases – all ten cases of influenza. But even if the vaccine is only 40% effective, we would still prevent four cases, if all 100 were immunized.

Due to the large burden of illness caused by influenza, even a vaccine with a lower effectiveness can still prevent thousands of cases. The interim VE estimates from the Canadian Sentinel Practitioner Surveillance Network, show that the vaccine was 68% last year effective overall and 72% effective against H1N1 specifically that with predominant strain.

For high risk groups, this vaccine was 88% effective for young children and 64% for adults over the age of 65. But too little influenza A H3N2 were circulating early in the season to obtain an estimate. The final estimates which are expected soon, are expected also to be low.

So don’t forget, when we’re looking at these assessments of vaccine effectiveness, we are looking at four different vaccines really in one, if it’s a quadrivalent vaccine. So there are four different illnesses that we’re actually assessing against.

The implications of low vaccine effectiveness – existing influenza vaccines are by no means perfect; however, they are currently the best available line of defence against influenza and even when there is a less than ideal match, or lower VE against a circulating influenza strain, the possibility of a low VE should not preclude vaccination, particularly for people at high risk of complications.

It’s important to note that vaccinated individuals are still more likely to be protected against influenza infection, compared to those who are unvaccinated. They are protected against several different influenza strains with one dose of vaccine. And it may lessen the severity of their symptoms even if they are affected.

So that’s the end of the first part of my presentation. I’m now going to turn the microphone back over to Dr. Evans, who will tell you about the AMMI Canada’s guidance on the use of antiviral drugs for seasonal influenza.

Dr. Evans:

Thanks Ian. So those of you who attended the seminar last year, you’re going to see a fair bit of stuff that I already previewed and we’re now published in our paper, which appeared in JAMMI (Official Journal of the Association of Medical Microbiology and Infectious Disease Canada). And there is a link to the paper on one of the last slides that Dr. Gemmill is going to show you afterwards. So we’ve now had this published and confirmed and so I’m going to review those again for you.

We identified a number of principles within the document, including sort of the general principles of treating influenza with antivirals, talked about the treatment of non-pregnant adults, as well as infants, children and youth and also had specific sections on what to do with immunocompromised patients, pregnant women. And then I think the section which enjoyed a lot of discussion, which is the use of either post-exposure or pre-exposure of prophylaxis, versus the concept of early therapy.

So the general principles we identified is that if you’re going to use an antiviral for influenza, it should be initiated as rapidly as possible. There was fairly good evidence to support that as a strong recommendation. I don’t think 48 hours pans out to be as important when we’re talking about certain select population. So I would just emphasize that.

We also mentioned that antiviral therapy should be initiated if the influenza was severe enough that it required a patient to be hospitalized, if they were identified to have progressive, severe, or complicated pneumonia. And we defined what those are in that document and you can have a look at the table there. Or, if they were from a group considered to be at high risk. Those included patients like pregnant women, patients suffering from diabetes, or cardiopulmonary diseases, etcetera.

In general, we felt that healthy patients with relatively mild self-limited influenza aren’t really likely to benefit from neuraminidase inhibitor therapy, remembering that by and large, that’s the only group of drugs that we currently use in Canada are the neuraminidase inhibitors. Baloxavir is available in the States, but not in Canada and probably is going to be a very limited drug. A question had been posed about that earlier.

Patients though, if they seemingly have just a mild case of influenza – and recognizing influenza is a nasty disease – should be advised though of symptoms and signs of worsening illness, because that would warrant a reassessment. And the treatment duration should routinely be five days.

This is the algorithm from our paper on the treatment of mild, or uncomplicated influenza in adults, where we’ve divided people into those with risk factors, versus those without risk factors. And recognized that if there were risk factors present – even if it’s over 48 hours since the onset of illness – you should still consider antiviral therapy and remind patients about the potential for progressive disease to develop and what those signs and symptoms they should watch out for.

So this basically again, goes over that issue of duration of therapy and recognizing that 48 – although that was the marker used in clinical trials – may not necessarily be applicable to those who may have risk factors, etcetera.

When it came to progressive, severe, or complicated influenza, though, this algorithm is what we put in the paper which said basically one of the first things you should consider is hospitalization. And possibly, depending on their assessment at the time of being seen at the hospital, whether they should be in ICU. And also to remind clinicians about the fact that sometimes an acute primary bacterial pneumonia can present in influenza season, which may have an impact.

But antiviral therapy should be started immediately. And if the patient is not responding to Oseltamivir, which is the agent that we typically use that you need to consider other diagnoses and of course influenza B where Oseltamivir probably doesn’t have as much activity as Zanamivir does. In those with moderate progressive, severe, or complicated influenza then, the key reminders are consider hospitalization, start Oseltamivir and again if they have normal renal function at a dose of 75 mg twice a day, even if the interval from onset of illness is greater than 48 hours.

In children and youth, with mild or uncomplicated influenza disease, it’s important to remember that under age one year, you need to consider it on a case-by-case basis and you may need to get some expert advice, either from a pediatrician or pediatric ID person.

Those between one and five, although they are at some risk for more significant disease, don’t routinely require antiviral therapy, as well as those over age five, because they fall into now a risk category, which is relatively low.

When it came to modern or progressive, severe, or complicated influenza in children and youth and infants, again hospitalization, start treatment immediately and even if that interval is greater than 48 hours, you should begin antiviral therapy just because of the data that shows that starting antivirals actually has an impact on reducing complications and potentially even death.

For immunocompromised individuals, we said treat as soon as possible without regard to the duration of their illness. And that’s simply because in those immunocompromised individuals the progression and evolution of influenza can be difficult to predict and we do recognize that they may be at added risk, even if they’ve been immunized.

So early initiation of therapy for a symptomatic infection though, is preferred over post-exposure prophylaxis, simply because excessive use of post-exposure prophylaxis we think, may drive resistance problems.

In pregnant women, you should use Oseltamivir. Standard doses are recommended, even though pregnant women do tend to eliminate drug faster because their creatinine clearances rise and they have a higher plasma volume, but standard dose is given – should be given to a pregnant woman who develops influenza, either laboratory proven, or with clinical characteristics of influenza at a time when you know influenza is circulating in your community.

So post-exposure prophylaxis, versus early therapy. You already saw me mention this that early therapy we really prefer over post-exposure, due to the problems of emerging drug resistance if post-exposure prophylaxis were to be used broadly.

So in people who have been exposed to influenza – and you’re right, they’re going to develop it – what you need to do is develop a system to watch them closely and should they be – suddenly develop symptomatic infection, then start the therapy immediately, rather than giving them the drug when they’re still well, worried about the potential of transmission. And that’s because transmission of influenza, even in exposed susceptible individuals, is actually not 100%. And Dr. Gemmill touched on that when he looked at things like the attack rate.

We do think about post-exposure prophylaxis however, to control outbreaks in closed facilities and most of the provincial jurisdictions across the country have developed some guidance into what to do in long-term care institutions, which is probably the most common closed facility you’re going to see this. When to use antivirals in combination with ensuring that vaccine administration is also done to control an outbreak, especially in individuals who may not have been vaccinated, even though they should be.

Pre-exposure prophylaxis, which is to start prophylaxing people who are risk, before they’ve even ever had any sort of contact with influenza is a much more difficult topic. There’s not lots and lots of data on it. But we did say that there could be selective use of pre-exposure prophylaxis as a bridge to vaccine induced immunity in a period of time when you were vaccinating someone, recognizing it may take up to 14 days to develop an actively effective immune response.

And on occasion – at least to protect patients at high risk in their close contacts – when the circulating strain that is in the community at the time may not be well-matched with seasonal influenza virus strains that sometimes can be a bit tricky, because our understanding of how effective a vaccine is, sometimes takes a little bit of time to work on and to get the data out.

This is our algorithm for what to do in terms of using Oseltamivir and Zanamivir prophylaxis in close contacts of suspected or lab-confirmed cases. And recognizing that you can see on the left-hand side of that slide, residents in closed facilities, we do tend to sort of push at least the concept of post-exposure prophylaxis.

For others, it really is a matter of whether or not risk factors exist for the potential for influenza complications. And if they are, there may either be presumptive therapy, or at least early treatment if they develop signs and symptoms.

Lastly, there’s this whole issue about what to do in seasons where the low – there may be predicted low vaccine effectiveness. We published this a few years ago, because in 2017/2018, there was some concern and our plans are to update that paper. So we’re hoping to have that out probably by around November or December.

But recognize that you may want to consider antiviral therapy for individuals who are at high risk of serious influenza complications, irregardless or regardless of whether they’ve received the seasonal influenza vaccine or not, if there’s a concern about a vaccine mismatch.

Antiviral therapy in those individuals certainly should be started as soon as possible and as much as possible. The earlier you do it, sometimes the better. And you may not necessarily consider their influenza vaccination status. So that can be relevant in some years where there looks like there may be an issue with matching of some parts of the influenza vaccine.

So at that point, I’m going to turn it back over to Dr. Gemmill to sum up the key messages and some of the resources you can use.

Dr. Gemmill:

Well thanks again very much Gerald and I’ll be very brief here, because I see there’s lots and lots of questions. First of all: key messages to communicate about influenza prevention. Influenza vaccine is still the safest, longest-lasting and most effective way to prevent influenza.

Everyone six months of age and older may get the vaccine and the only reason we don’t give it people under six months is, as I’ve already mentioned, is it doesn’t work as well. It is especially important for people who are at high risk of complications and those who are especially capable of spreading influenza to those at high risk and it’s important to get vaccinated each year to stay protected, because viruses change from year to year and effectiveness can wear off.

Also the vaccine protects against several different strains each season and even when there was a lower vaccine effectiveness against one strain, the vaccine can still provide protection against the two remaining strains. So every year, we’re trying to guess what is going to be circulating and we do – SAGE does their very best possible analysis of this, but sometimes there’s still mismatches that can occur.

But if, for example as it happened last year when there was a double kind of season, with both H1N1 and H3N2, there is protection against more than one of these strains. In addition to getting vaccinated, other measures to prevent getting the flu are the ones that you are all familiar with, in terms of hand hygiene, coughing and sneezing in the Canadian way in the bend of our arm, not going to work when you are sick and keeping surfaces clean.

And there are a number of resources for you that I’m going to present very quickly here. You will be receiving these slides, so you will have all the tables that I provided for reference. And these references as well – so this is a statement by NACI that you can refer to, the AMMI Guideline that Dr. Evans has just gone over in some detail. The Public Health Agency of Canada also offers free resources and there’s the website for you on influenza and influenza vaccine. Immunize Canada is a very good source of resources for you and they – their website is listed there for you when you get the slide deck.

And finally, it’s really I think good to sign up for FluWatch if you are interested in what’s happening with influenza through the influenza season. You can get weekly updates that tell you exactly what’s going on across Canada, both in terms of the strains that are being isolated, the sentinel physician reports and much, much more. It is a very good resource to have.

And with that, I am going to end this part of the presentation and I’ll turn it back over to our moderator, Aleksandra, for the question session.

Aleksandra:

Okay. Thank you very much Dr. Gemmill and Dr. Evans. We have about ten minutes to 1:00 o’clock eastern time. Like I said in the beginning, our presenters are willing to stay a little past the hour to answer as many questions as possible. A number of questions have come in, so I will just try to post these questions to our speakers in the order that they have been coming.

So the first question is, given the two types of inactivated trivalent influenza vaccine for the geriatric population, who should get the high dose vaccine?

Dr. Gemmill:

Okay. Well I think I should take that one if that’s okay Aleksandra and I’m sorry I wasn’t clearer during the presentation, but just to refer people to the statement for this year, Table 1 of the statement lists the various vaccines that are available for various age groups – the ones that they’re licensed for – and for people 65 years and older, there are four options.

There’s a standard dose IIV3. There is a standard dose IIV4. There is an adjuvanted IIV3 and a high dose IIV3. And this makes things complicated for people to make a decision about which vaccine to choose. All four meet the minimum criteria. They have all shown through the licensing that they are not inferior to the standard that has been put forward, but there have been very few head-to-head trials, because they’re so expensive to conduct.

And so we don’t have a lot of good data to be able to advise us about which ones of these vaccines is the optimum one to use. There is, however, I think growing and mounting evidence that NACI has considered, about the value of the high dose vaccine.

And don’t forget the adjuvanted standard dose vaccine has got 15 micrograms of each of the components. The adjuvanted vaccine has 15 micrograms of each of the component plus the adjuvant that will theoretically cause greater immune reaction and therefore provide for a higher and longer lasting protection. And the high dose actually goes up to 60 micrograms of each of the components of the vaccine. And so therefore, you’re getting four times the dose.

When we looked at the data on these various vaccines, the one we were able to say does provide some – looks like it’s going to have a reasonable chance to providing better protection in this population that is – because they’re immunosenescence, as I mentioned, is already at somewhat increased risk of complications for influenza – it looks like the high dose could be – provide a higher level and longer lasting protection for this population.

And that’s why in the Table, NACI said for the individual – when you have an individual patient you’re looking at and they’re in your office, what should you do? When available, IIV3 high dose should be used over the standard dose, given the burden of influenza A H3N2, as I mentioned in the presentation and the good evidence of better efficacy compared to the standard dose in this age group.

There’s insufficient evidence to be [able to make] individual level of recommendations on the use of IIV3 adjuvanted, or IIV4 standard dose over any of the other four. And so therefore, we just can’t say.

So for the individual patient, yeah probably give the high dose if you’ve got it handy. If you don’t please do give any influenza vaccine that is licensed for this population, because any influenza vaccine is better than no influenza vaccine.

On the same table, under Public health level Decision-making, the issue here is that the cost-effectiveness assessments have not been performed. And so therefore it’s very hard to look at what you’re buying, in terms of value for money on a population basis.

And that’s why some provinces have made different decisions about which vaccine to offer for you to give to people 65 years of age and over. These people should receive some vaccine and if your province provides high dose, you need to respect the criteria for which they have been done. So please do check with your provincial or territorial representative. I think I’ll stop there, unless there’s any further clarification, Aleksandra.

Aleksandra:

Thank you. A similar question – what is the difference between the high dose and the adjuvanted inactivated trivalent vaccine for the elderly? And is one better than the other? You may have mentioned this briefly already. But if you can just recap an answer to that question. Dr. Gemmill, can you hear me?

Dr. Gemmill:

Sorry. I guess I was on mute. Excuse me. Yeah. So very briefly, we haven’t got any head-to-head studies between the adjuvant and high dose. The adjuvanted contains 15 micrograms, but an adjuvant that stimulates the immune system more. So theoretically it might provide some better protection.

We haven’t been able to, how should we say – identify the data is consistent. And don’t forget – what is the importance of vaccine against four different infections over a whole bunch of different seasons, when different ones are prevalent in different years, it’s really hard. It’s really very hard to figure out which quote is better.

I think the best I can say is because it’s got a much higher dose for you looking at people of this age group – if you have it available or they’re willing to pay for it, or it’s in your provincial program, it looks like the high dose is a better option, because the H3N2 is the one that is causing the greatest amount of complications and other negative consequences of influenza for the people over the age of 65. Thank you.

Aleksandra:

On a similar note a question came in that last year there were multiple cases when people got the high dose vaccine who had significant side effects. Are these similar side effects expected with the high dose this year as well, from your experience?

Dr. Gemmill:

Well it looks like what happens with any new development in vaccines, if when we develop vaccines that are thought to give us better protection, sometimes we end up with more side effects. In other words, the immune system is reacting more in some ways as well. Because high dose contains four times as much antigen, one can postulate that there would be more side effects from it.

I have not heard anybody say that they’re too – how would you say – unpleasant – to avoid this vaccine and as a matter of fact, I think NACI would clearly say that if it is available to you, or to your patient, that this is the one to choose even though it may cause more, you know a sore arm, or something like this.

Please also be advised, however, that the matching of the strains is really important. So even a high dose vaccine won’t provide protection, if we’ve got the match wrong. And so it’s better if there is a good match potentially. And a year like last year, when the H3N2 vaccine efficacy was lower, that’s perhaps a good reason to give the high dose vaccine to this age group, because they may get some more protection, even if the vaccine effectiveness is not as good.

Aleksandra:

Okay. Thank you. A question for Dr. Gemmill – you mentioned the live attenuated influenza vaccine is not available in Canada, due to shortage supply. Is it because none of the provinces have ordered this vaccine, due to H1N1 component’s questionable lower effectiveness a few years ago? Could you comment on this question?

Dr. Gemmill:

Well, LAIV has been through a lot of ups and downs over the years as you’ve just mentioned. I think it was around the 2015 or ’16 season, somewhere in there – LAIV was taken off the list by the Advisory Committee on Immunization Practices in the U.S.A. because it looked like the vaccine effectiveness was in the negative area.

So LAIV has had that kind of history. It’s not widely used, or at least as widely used in Canada, as it has been in some other countries. So – and I’m only speculating here – the U.K. has got a program that uses LAIV for kids and so therefore, the manufacturer of course, is going to be supplying that program first. So when they have less available then the people who – other countries that are using it in a routine regular way in a vaccine program – like the U.K. does – I guess are not getting it.

But if people need to know more about the shortage – or not the shortage but the lack of availability of LAIV – they should go to Drugshortages.ca. AstraZeneca really is the ones who have the answers to this question and as I understand it there is more information at that website. Thank you.

Aleksandra:

Thank you very much.

Dr. Evans:

Aleksandra, I just wanted to – it’s Gerald here. I guess the number of people noticed that the guidance for the antivirals is not on the AMMI Canada Website and it is not. And I just posted the link. If those of you who are listening just look at the Chat Box you will see the link.

Aleksandra:

Okay.

Dr. Evans:

It sort of shows up as a blue text, because it’s a corrected link and it actually takes you to the PDF of the article that you can download.

Aleksandra:

Okay. Thank you. There was a question about Oseltamivir in the dosing around pediatric population. Can you comment on that?

Dr. Evans:

Yeah. So I actually answered that question in the Chat Box –

Aleksandra:

Oh okay.

Dr. Evans:

– to [Caitlyn] who had asked it. And we have the Table in the Pediatric – there’s a Table in the article that talks about it, because kids are always a little bit challenging when it comes to weight-based dosing and of course recommendations, there aren’t really any for kids under the age of one year.

Aleksandra:

Okay. Could you comment on the resistance to Oseltamivir in influenza – how common is it?

Dr. Evans:

It’s actually – it is described – we know the mutations that confer it, but it’s very uncommon and certainly has not been seen extensively in any of the circulating viruses that were from the Southern Hemisphere, nor last year in our Hemisphere.

So at the moment, Oseltamivir resistance is a potential possibility, but has not been seen widely, so that’s a good point about – that antivirals still are useful.

Aleksandra:

Okay. Great. What are the side effects of Oseltamivir and Zanamivir?

Dr. Evans:

I’ll talk about Oseltamivir, because it’s used more – one key thing is to remember there is a – although it’s not – it you know, is not as toxic as the old adamantane antivirals were. You still have to know the renal function of your adult patients, because Oseltamivir does have some neurotoxicity associated with it. It’s described more when given to children than to adults. But if you give full dose Oseltamivir to an adult who has some significant renal impairment, there is the potential for neurotoxicity usually manifested as seizures.

Other than that, what we know is about 10% of people who take Oseltamivir will develop nausea and may have some vomiting. With Zanamivir, the big problem is just related to exacerbations of reactive airways disease. So if you give Zanamivir, which is an inhaled product to someone who has asthma and/or COPD, there may be some worsening of their wheeziness and their obstruction, but those are the sort of main common side effects.

Aleksandra:

Okay. Great. Thank you. Another question came in regarding long-term care facility outbreak and should antivirals be used? And is it for the entire duration of the outbreak? Or for how long?

Dr. Evans:

That’s a great question. It pops up every year. We tend to sort of have this view that if you’re going to use it in that setting, you probably don’t need to use it longer than about 14 days. And if you look at most outbreaks that pop up in long-term care homes, that’s about the longest that they tend to be present.

I think if the outbreak lasts longer than that – and there may be some issues that cause that – then it has to be taken on a sort of case-by-case basis, as to whether or not you continue it beyond a sort of 14 day period.

Aleksandra:

Okay. Great. Another question – going back to the shortage of the vaccine supply – a question regarding updates. Will NACI create updated recommendations on the priorities and who should receive the high – among the high risk population who should receive the vaccine first, provided that the shortage will be maintained?

Dr. Evans:

Ian has to unmute his phone.

Aleksandra:

Dr. Gemmill, can you hear us?

Dr. Evans:

Maybe we lost him.

Aleksandra:

I’m not sure if he can hear us. Maybe –

Dr. Evans:

I’ll just sort of chime in. The question in terms of shortages and availability is oftentimes, you know is under provincial jurisdiction in terms of what they ordered and what became – what becomes available, etcetera. So I think that was the genesis of the question – what do you do if there’s shortages?

Aleksandra:

Mm-hmm.

Dr. Evans:

Then you know, although we recommend high dose for adults – for adults over 65 I should say – then you may need to revert to the regular dose IIV3, or an IIV4 for an older adult, just recognizing that you may not get the same amount of immunogenicity.

Aleksandra:

Okay. Is – there was a question regarding thimerosal – or which vaccines do not contain thimerosal?

Dr. Evans:

I’m not – I should be an expert on this area, but I’m not. Thimerosal is actually not used virtually in any vaccine. The only ones that it shows up on – it used to show up on are multi-dose vial vaccines, which are almost non-existent nowadays.

And just [Crosstalk] I mean I can go into the whole issue that thimerosal has – uses ethylmercury – sorry ethylmercury not methylmercury – and it’s methylmercury that’s toxic. And there’s no evidence that thimerosal ever had, or produced substantial mercury-based toxicity in recipients of vaccines, in which thimerosal was used.

Aleksandra:

Okay. I think Dr. Gemmill got cut off and he is trying to get back on, from what I can see in our Chat. So I’m not sure if we’re going to be able to get him back on.

Dr. Evans:

And one of our participants again pointed out that if you have prefilled syringes or single dose influenza vaccine, they are thimerosal free. But I think even the multi-dose ones, don’t tend to have thimerosal in them. That was created, of course by the fact that that is a common concern amongst those who are vaccine hesitant – that somehow, it was the cause of this unseen vaccine safety issue – or vaccine toxicity issue.

Aleksandra:

Okay. I have a question – another question here. Would you consider a retirement home a closed facility, or not?

Dr. Evans:

And that’s a good question. I saw that one and I couldn’t figure how to answer. It depends – some – in some jurisdictions, because it’s a closed population, you know and especially in retirement homes – they may have a common area like a dining-room where they go for meals – some have decided that those are considered to be closed facilities. And they certainly reflect that as a population. But in some places, they are just considered to be sort of really just a small community which may share some things in common.

So I don’t know that I’ve ever seen anybody define it. It’s a great question that I may raise with my colleagues in our working group. Because I’ve seen this question before and I don’t know how to really answer it. Certainly in a retirement home, if there’s a substantial number of cases, it may be that Public Health in your jurisdiction or your province, may decide that that reflects an influenza outbreak and declare it.

If you’re in an outbreak situation then you can apply much of what we’ve talked about, in terms of the use of antivirals in an outbreak in a long-term care facility.

Aleksandra:

Great. Thank you. I have another question. Can you comment on if the influenza vaccine would be recommended for travellers, travelling between hemispheres more than once a year – should they receive more than one vaccine?

Dr. Evans

Yeah. I think Ian is still having some trouble getting on. That’s a – it’s an interesting question. I mean the Southern Hemisphere vaccine this year used a 3C.2a1b clade H3N2 virus, as their vaccine component.

Here in the Northern Hemisphere, we’re using a 3C.3a clade H3N2, so they do – they do differ in that sort of component. I – it’s really hard to say. I mean the immunogenicity of influenza viruses does last for a period of time. It does wane after about 12 months, but if you’re in the – you know, there are inter-seasonal periods in those Southern Hemispheres.

So if the dates of your travel are in an inter-seasonal period, I don’t know that I would worry about it excessively. There’s no harm in getting more than one vaccine shot, as far as we know. We don’t – haven’t really defined whether there’s anything called vaccine interference that may arise.

But you’re probably okay getting what you’ve had and I think if it’s been – if you’re getting close to that 12 month period, you may want to consider getting the vaccine for the next – for where you’re travelling to – recognizing that you can’t get the Southern Hemisphere vaccine in the Northern Hemisphere. You actually have to travel down there first to get it.

Aleksandra:

Okay. Somebody would like to know your thoughts or Dr. Gemmill’s thoughts on – high dose vaccine may cost more, but has it been compared to the cost of morbidity or mortality? Did you want to –

Dr. Evans:

Oh that’s a great –

Aleksandra:

– like to comment about it?

Dr. Evans:

Who’s the pharmaco-economist out there? That’s a really good question. No. I haven’t – I have not seen the costing data. That’s a very good question to ask, which is – is the cost, the higher cost of the high dose – does it produce improvements in outcome and what’s the cost per QALY (quality-adjusted life year)  gained? In other words, you know, is the incremental cost effectiveness ratio (ICER) acceptable within a cost effective vaccine?

I have not seen that data. I think somebody has been working on it, because there was an abstract presented at a meeting where they tried to explore that question. But the answer is, we don’t know from an economical point of view, or economics point of view, whether or not it’s worth the cost of the added high dose.

And it looks like Ian’s back – Ian they were just talking about ICER.

Dr. Gemmill:

Yes and so that’s going to be a consideration for – a future consideration for NACI. We’re heading into the NACI plus, which is the recommendations not only for effectiveness of vaccines, but also cost effectiveness.

So stay tuned on this one. It’s – as you said Gerald – there’s not much available now. It’s going to be a difficult task to complete, but we’re going to do our very best to be able to provide that information to provinces and territories, so they can make informed decisions about using this vaccine more widely in a publically funded program.

Dr. Evans:

Yeah.

Dr. Gemmill:

And I apologize. I got cut off. There was a question I was about to answer. So I’m happy to go back to that Aleksandra, if you wish.

Aleksandra:

I’m trying to find the question that I posed to you – before I realized you were not here, I mean.

Dr. Evans:

Okay.

Aleksandra:

I have [Harpa] helping me here, because there’s quite a few questions coming in and –

Dr. Gemmill:

There’s a [Crosstalk] number of questions, absolutely. So go on to something else as we wait for that then.

Aleksandra:

Okay. I think this has been answered before, but I will pose this question as somebody is asking. Do we have to consider creatinine clearance levels when giving vaccine to the elderly?

Dr. Evans:

Yeah. And I just commented on that and I will re-comment, because it looks like Irene Armstrong posed this question. And I was also on that PHO Teleconference yesterday.

So the problem is – is that if you overdose an elderly person with a substantially low creatinine clearance with Oseltamivir, you can potentially produce neurotoxicity which can manifest itself as seizures. I think what the presenter yesterday was getting at, is that certainly compared to adamantanes, it’s not as severe with, you know with amantadine and rimantadine, we really had to be careful.

But I would still advise caution in a patient who you suspect may have, or you know has some degree of renal insufficiency, to look at the dosing recommendations that we have in our paper, on how to adjust it based on the creatinine clearance.

So there can be a safety issue with Oseltamivir in elderly individuals who receive too much based on their inability to clear the drug completely.

Dr. Gemmill:

And I see in the Chat Box –

Aleksandra:

Okay.

Dr. Gemmill:

– there’s a question here about – do you need to have the creatinine clearance for the vaccine? And someone from – has already answered the question, which is that the creatinine clearance is not relevant when it comes to vaccine. Every person with renal disease should receive influenza vaccine to protect them against influenza.

Aleksandra:

Okay. I do have the question that was – that you got cut off on, when I was in the middle of asking you this question. It’s can you comment on the influenza vaccine, whether you would recommend it for travellers between – who are travelling between different hemispheres, more than once a year? I think –

Dr. Gemmill:

Yeah. This is a tricky question, because as everybody knows the influenza vaccine – sorry the influenza strains can vary from time-to-time and place-to-place. And that’s why the Strategic Advisory Group of Experts makes recommendations for the Northern Hemisphere for our winter and for the Southern Hemisphere for their winter. I think that the best – and then there’s a whole issue of availability of these vaccines as well.

So there are a couple of options here. One is that if someone is going to the Southern Hemisphere during our summer – which is their winter – sure if there is influenza vaccine around, it may provide some assistance if the viruses have not mutated or drifted, or shifted too much.

Another option for people who are at high risk and do not want to get influenza, is to inquire about receiving that vaccine once they arrive. It does take 10 to 14 days to be effective, but it may be better than having no vaccine at all.

So those are the two options I can think of. It’s just that it’s different in the Northern Hemisphere and the Southern Hemisphere, because of the differences that can occur in the time that elapses between our winter and their winter.

Aleksandra:

Great. Thank you. Another question – when you looked at the effectiveness of the vaccine, did you look at the effectiveness of FluMist versus injection?

Dr. Gemmill:

Well again, the interesting thing about influenza vaccines, is that they are licensed based on their demonstrated immunogenicity, not to be inferior to what has already been demonstrated to work. And this is because influenza vaccine – it’s very difficult to look at – to look at the specific head-to-head effectiveness of two different vaccines.

So LAIV, yes a few years ago, the Americans – in the American data – not everywhere but in the American data – they – it looked like there was a negative vaccine effectiveness, which meant that it provided no protection at all. Or some people might even attribute it as making people susceptible to influenza, which I hope wasn’t the case.

But that – there was a number of explanations for that – was that the virus used in the growth medium, was it some insult that occurred by temperature? Because don’t forget, this is a live virus and so therefore, it’s susceptible to temperature insults. Did something happen in transportation that might have caused this to happen?

So all this to say that LAIV – even though it’s not going to be marketed this year – when we did have it, it was a vaccine that was demonstrated to work. And as we know, all the influenza vaccines from – depending upon the year, the strain we’re looking at and so on – there have been examples of low vaccine effectiveness. And I think this was just one of them.

So that’s I think really at the moment all I can comment on it. And in a way, because we don’t have the vaccine this year, it’s not going to be available for children, in any event.

Aleksandra:

Okay. Great. Sometimes we have given the vaccine at the end of the season to someone. Is it okay to give the vaccine at the beginning of the next flu season? So that would be two in one year. Somebody would like to know your opinion on that.

Dr. Gemmill:

Yes. Absolutely no problem with doing that. My advice would be to give it as early as you can when it’s available, because you never know when you’re going to get an early season, but there’s no downside to providing it in this one late in season one and then early in season two.

I would actually recommend doing the latter. Whenever you have the chance to give it early, is a better option than giving it late in the influenza season, because the – by the time the vaccine is given – if it’s given late influenza may already be circulating in that community and the vaccine may be given too late to be effective for that person.

Aleksandra:

Thank you. I think we covered most of the questions in the Chat Box. Some of the questions have been answered by the participants, which we really appreciate. And I will finish off with a couple of last questions.

Are there any statistics to date, on how effective this year’s vaccination will be in Canada? And the second question is – when is the flu vaccine going to be available, I guess Canada wide, province-by-province if you know this already?

Dr. Gemmill:

Well I’ll take the first crack and then Gerald may want to pipe in as well. As to availability, my advice would be to ask your local Public Health Agency, or Provincial Ministry of Health, because they’re the ones who will know the most about when the vaccine will be delivered and will be available.

It’s hard to predict what’s going to be circulating – it’s hard to predict how well the vaccine is going to work from year-to-year, based on mismatches, or simply on some of the other factors that reduce the effectiveness of the vaccine.

So now there’s also the worry that the vaccine that is – has been recommended for the Northern Hemisphere addresses the organism that was most prevalent in the U.S.A. and not so much in other parts of the Northern Hemisphere.

So that is another worry. But I think it would be very – how should we say – ill-advised for me to try to predict how bad the influenza season is going to be at this point in time and how well the vaccine is going to work. That’s something we can really only see in retrospect and kind of speculate in prospect. And Gerald, did you have anything to add to that?

Dr. Evans:

Yeah. I guess my issue is – is if this pans out to be an H1N1 season and/or B season, I think we’re in pretty good shape. There’s a very good matching based on Southern Hemisphere and last year’s season that we’re going to cover it.

The challenge is going to be the H3N2 side, just simply because the decision to put a 3C.3a clade of the H3N2 vaccine strain, was based on the fact that that was what circulated in the U.S. last season. In Australia in the Southern Hemisphere, what we’ve got from data now suggested it was actually a 3C.2a1b strain that circulated. And if so, then that is a mismatch.

And so it really depends, as Ian said – what virus emerges here in the Northern Hemisphere. But I would – you know, I can’t really underscore how important it is to get your flu shot. If it’s a [B and A H1N1] season, you’re going to be well-protected.

And maybe it’s going to be a [3C.3a] season, like the Americans had – in which case then, we’ve got a good match. So people really should get their flu shot, because generally there’s virtually no down side to it and a remarkable up side that you’re going to benefit from and those around you who are going to benefit from it.

Dr. Gemmill:

That’s right. I mean I think the message is, safest, longest lasting and most effective – even though it’s not 100% – the most effective way we have of preventing this – what could be quite a nasty disease and may actually cause some matching complications as well.

Aleksandra:

Thank you very much. I think with this, we will conclude our webinar. I just want to thank everybody for attending and especially for all of the 200 participants who stayed on 20 minutes past the hour. So on behalf of the NCCID and Public Health Agency of Canada, I would like to thank our speakers for an informative presentation, as well as all of you for participating in today’s webinar. We hope you found it useful.

The webinar recording, as well as the slides, will be shared with all who registered, within the next week. We will now ask you to complete the evaluation form at the link that you see on your screen. Hopefully we can go back to it, or that link will be emailed to you as well.

Your feedback is very important to us and essential for planning our future events. Thank you and goodbye for now.