Activity Transcript

Segment 1

Andrew T. Pavia, MD, FAAP, FACP, FIDSA: Hello, I'm Andrew Pavia, George and Esther Gross presidential professor and chief of the division of pediatric infectious diseases at the University of Utah, and director of the hospital epidemiology program at Primary Children's Hospital in Salt Lake City. I want to welcome you to this program titled: What Is New with the Flu: Prevention and Treatment for the 2022-2023 Influenza Season.

In this program we'll review recommendations for antiviral use in treatment and chemoprophylaxis, populations at high-risk for influenza-related complications, and influenza in pediatric populations. These topics will be covered in 3 segments, so let's move on to the first segment.

In this segment I'm joined by Dr Michael Ison. He is professor in the division of infectious diseases and organ transplantation at Northwestern University Feinberg School of Medicine in Chicago, Illinois. And the title of the segment is: Treating the Flu: What Do You Do?

Welcome, Mike.

Michael G. Ison, MD, MS, FIDSA, FAST: Thanks for having me.

So, what we'll start with is a review of the available antiviral medications that are available for the treatment and prevention of influenza. There are 2 classes of antivirals that are currently available. There are the neuraminidase inhibitors, oseltamivir, zanamivir and peramivir, and the polymerase inhibitor baloxavir. All of these drugs are active against influenza A and influenza B. And all are recommended for treatment, with prophylaxis being an option for oseltamivir, zanamivir, and baloxavir.

The mode of delivery is slightly different with each of these. Oseltamivir and baloxavir are given as an oral delivery. Zanamivir is inhaled. Peramivir is given intravenously (IV). The age for use is slightly different for each of these agents, with oseltamivir being available for all age groups for treatment, and for prophylaxis in individuals greater than 3 months of age. Zanamivir is approved for treatment in patients 7 and older and chemoprophylaxis in greater than 5 years of age. Peramivir is approved only for treatment and baloxavir is currently approved for treatment and postexposure prophylaxis in patients 12 and older.

Dr Pavia: Mike, what do we know about how well these agents are used? That is, how often are they prescribed for patients for whom there're indications?

Dr Ison: Yeah. That's a great question, Andy, and one where I think we really need to be doing better. As you can see from this study published just a few years ago, with about 1300 patients with influenza-like illness, only 20% of those patients were actually prescribed antivirals. And really, that is far lower than we would ideally like. Some of this may be that we know that patients sometimes come to seek care later during their clinical course. But there have been other studies that have looked at this.

What's of great concern is underutilization is greatest in some of our highest risk populations. Those less than 2 years of age, where only about 11% of these children received a therapy. And those patients over 65 years of age, where only about 22.6% of patients received therapy. These are 2 of our highest risk populations. We know that early therapy reduces the risk of severe infection and complication in these patients, and yet we're really not delivering the treatment well to these patients.

In this additional study, which I actually find to be really interesting, this looks at high-risk patients that are presenting within 2 days of symptom onset that really would be eligible for treatment. And despite that, only 15% of patients overall received therapy. And even those with laboratory-confirmed influenza, we only got the treatment up to about 37%.

So really, these data show that the majority of patients that would benefit from therapy, particularly these high-risk individuals, really are not receiving the best possible therapy for this infection.

Dr Pavia: These data are really kind of disturbing, particularly when you focus on the high-risk patients and those who present, clearly, early on, and who would qualify for treatment. Can you speculate on some of the reasons why those patients aren't receiving treatment?

Dr Ison: Yeah. I think it's a good question, and one where we definitely need more research to really understand: what are the drivers? Clearly, one driver is that patients aren't necessarily seeking care early on, within the first 1 to 2 days after symptom onset. That may change in the era of COVID-19, where patients are more attuned to respiratory symptoms and the desire to get tested. I think the challenge now is: are they getting tested for influenza or just COVID-19?

I think the other challenge is, is that providers feel uncomfortable, for a range of reasons, in prescribing these medications. What I find interesting, which we didn't talk about, is despite only 37% of the high-risk patients with polymerase chain reaction (PCR)-confirmed infection getting antivirals, a large proportion of these patients -- about the same percentage, about 40% -- also received antibiotics, which probably aren't needed in those patients. So, I think it's an opportunity not only to help the providers better understand the benefits of these therapies, but also the potential harm in giving things like antibiotics when they're not needed.

Dr Pavia: Yeah, those are all really good points. I suspect another issue is some confusion over the timeframe in which these drugs are active ii different groups and when the benefit is most helpful in those with low-risk influenza, as well as those who are hospitalized. Can you review, for us, the treatment recommendations? Who definitely should get treatment, and for whom is it an optional thing that we can offer?

Dr Ison: Yeah. So, I think the first and foremost thing is, if you're going to decide to treat a patient for influenza, giving them the therapy as soon as possible really provides the greatest benefit. There was an old study done early after the approval of oseltamivir, and it showed if you're able to get the drug into patients within the first 12 hours after symptom onset you actually get about a 4-day benefit in terms of clinical recovery. That goes down to about 1 day as you get closer to that 48-hour time window. So, the sooner we get the therapy, the better. This is particularly important in certain populations where therapy really should be delivered early. In hospitalized patients, the earlier you get the therapy on board the better, patients that have severe complicated or progressive illness and those at higher risk of influenza complication.

I think, even though we have more access to diagnostics, the current guidelines recommend starting the therapy as soon as you begin to think that the patient may have influenza. That empiric approach is beneficial. These medicines are incredibly well tolerated. In addition, if the patient doesn't have influenza, there's no concern for putting pressure on resistance since the virus isn't colonizing the patients as antibiotics would be.

For non-high-risk outpatients, this is where the guidelines say: consider early therapy in patients presenting within the first 48 hours after symptom onset. And again, the way that I always look at this is it's clearly been shown that patients feel better quicker. I think that's why we're oftentimes giving therapy for our patients with infections, not only to help them recover but to feel better and get back to normal activity as quickly as possible.

Dr Pavia: And you emphasized, for hospitalized patients, that the sooner you treat the greater the benefit. But there's certainly are data, aren't there, that suggests that there's some benefit, out to as long as 5 days after symptom onset, for patients who are hospitalized?

Dr Ison: Yeah, definitely. And I think this is an area where there's oftentimes confusion, where people are getting admitted and they're beyond the 48 hours and don't get antiviral therapy started. The data is clear, you get improvement in terms of outcomes, including mortality, if started up to 5 days.

We have shown that even if it's beyond 48 hours, but the therapy is started within the 6 hours of hospitalization, you're able to shorten the length of stay, reduce progression to pneumonia, and reduce mortality in those patients. So definitely getting those patients started early, even if it's beyond 48 hours, is a benefit.

Dr Pavia: It's probably helpful to our listeners if you'd go over the medications again, the dosages and the duration, so that they're more familiar and feel more comfortable prescribing these antibiotics, particularly if they're going to do it early or presumptively or over the phone.

Dr Ison: Yeah. So, there are a number of different medications that can be considered for patients presenting with influenza. If a patient is an outpatient, with a complicated or progressive influenza that's either proven or suspected, oral oseltamivir is usually the drug that we would turn to for these patients. With patients with a suspected or confirmed uncomplicated influenza, I think you can use any of our currently approved medications, oral oseltamivir, inhaled zanamivir, IV peramivir, or oral baloxavir. In those patients at high-risk of developing influenza complications, baloxavir has specifically been studied and is approved in that population. For hospitalized patients with suspected or confirmed influenza, oseltamivir is still considered the drug of choice for these patients. There were some thoughts that perhaps, in the hospitalized patients, using combinations may be of benefit. But recent publication failed to show significant benefit with that combination therapy, although there may be a reduction in the risk of resistance in those patients.

In terms of duration of the therapy, 5 days of therapy are recommended for oseltamivir and zanamivir, and a single dose of IV peramivir or baloxavir is appropriate. Baloxavir, unlike the other medications, is dosed based on weight, so that patients that are less than 80 kg are given a 40-mg dose and those 80 kg or greater are given an 80-mg single dose.

Dr Pavia: The studies that have led to licensure really focused on the duration of symptoms and time to clinical improvement, but other endpoints have been looked at. So, what other benefits have been demonstrated and are supported by the evidence?

Dr Ison: Yeah. So, what we have the greatest evidence for -- and this is predominantly in the outpatient population -- is that the early use of these therapies is associated with a shortening of fever and illness duration. So, the symptoms get better much more quickly in the patients that receive treatment than those patients that go untreated. There's also clear data that antiviral therapy is associated with a reduction in the risk of influenza complications, such as otitis media in children, pneumonia and respiratory failure in all patients. And this has been studied in both retrospective and prospective studies for the available antivirals. Among hospitalized patients, clearly antiviral therapy is associated with reduced death in hospitalized patients. And particularly when that therapy is started early after a hospitalization, shortening of the duration of hospitalization is been clearly demonstrated.

But it's important to recognize that the clinical benefit is greatest when patients are started early, ideally within the first 48 hours after influenza onset. In hospitalized patients, that benefit extends to 5 days. So, patients with a more severe progressive or complicated illness, patients that are hospitalized and immunocompromised patients, still likely receive benefit even being started after 48 hours. But again, getting that therapy started as quickly as possible after they present for care really provides the greatest benefit.

Dr Pavia: Thanks, that's a great review of treatment. One of the areas that we get a lot of questions, and I think there's a lot of questions, about the optimal use and when to use antivirals for chemoprophylaxis.

Dr Ison: Yeah. Well, I think the first thing, before we talk about drugs, is we have to remind everyone that the annual influenza vaccine is still the best way to prevent influenza. And our overarching goal should be to get patients vaccinated against influenza. And even if we're going to use chemoprophylaxis, because of risk of exposure to an individual, still recommending and delivering the influence vaccine is really critical. Because even if they got exposed early in the flu season there are other subtypes that may emerge later in the flu season that the vaccine can prevent and avoid the need for chemoprophylaxis.

There are 2 types of prophylaxis that can be given. Preexposure prophylaxis, which can be used in very limited settings, such as in nursing homes or other institutional outbreaks. They have been studied in immunocompromised patients that are expected not to mount a good response to the flu vaccine. But the most common way that the chemoprophylaxis is used is as a postexposure prophylaxis. So, when an individual is exposed to someone with influenza, this can be considered. It's not something that we routinely recommend for our patients because the virus can be replicating, and since we're using lower doses of some of the medications, resistance may emerge, and for most patients awaiting to see if they develop symptoms, since only a relatively small proportion of exposed individuals may become sick with influenza.

That being said, if you do decide that you would want to consider chemoprophylaxis, there's certain situations where they can be considered. All of these are appropriate for individuals 3 months of age or older. Those patients at high-risk of developing influenza complications, who have a contraindication to influenza vaccine, can get a prophylaxis for the duration of the flu season. Likewise, patients that are unlikely to respond to the vaccine, such as patients early after stem cell transplant or a lung transplant, can receive the seasonal prophylaxis as well. Patients who are not yet vaccinated and at a high-risk of developing complications from influenza can have a preexposure prophylaxis used while waiting for the administration of the vaccine. And likewise, close contacts of persons at high-risk of developing influenza complications, where vaccine is contraindicated or they're unable to take the vaccine, the chemoprophylaxis is an option for these individuals.

In terms of postexposure prophylaxis, really, I think that, again, this is an option for patients ages 3 or older, those at very high-risk of complications, such as severely immunocompromised patients in which flu vaccine is contraindicated, unavailable, or expected to have low effectiveness, and in patients that aren't yet vaccinated and who have household contacts of a person at very high-risk of complications from influenza, like the severely immunocompromised, are populations that we would consider giving postexposure prophylaxis.

For the neuraminidase inhibitors, these need to be started within 48 hours after exposure and continued for 7 days after the last exposure. Whereas, for baloxavir, this is administered as a single dose based on weight within 48 hours of exposure.

There are definitely some things to remember if you're going to use a chemoprophylaxis. One, even if this is given, you need to monitor the patients. And if they develop the symptoms, consider treatment, perhaps with a different drug. If you choose not to give prophylaxis, again, watch the patients closely and give them clear guidance to give you a call back if they develop symptoms, particularly fever or respiratory symptoms. If patients present for prophylaxis after 48 hours it's not recommended to give them the prophylaxis. And again, if the patient is on chemoprophylaxis, either pre or postexposure, and develop a febrile respiratory illness, they should really seek care to see if it's influenza or a different infection. And then antiviral medications are effective, about 70% to 90% effective, in preventing influenza if the virus is susceptible. So that if they are being used, it's a great option for these patients.

Dr Pavia: Thanks. So, the messages, I think, are: we use chemoprophylaxis sparingly, for our patients at the highest risk. We're careful not to give it after 48 hours. I guess the 1 group for which we strongly recommend chemoprophylaxis is for interruption of an outbreak in a nursing home, where it really is our best tool. And we use it frequently in that setting.

Mike, thank you so much. This has been an excellent review. Hopefully our audience will find it really helpful in taking care of patients this coming winter.

Dr Ison: Thanks. It was great joining you.

Segment 2

Andrew T. Pavia, MD, FAAP, FACP, FIDSA: Hello, and welcome to segment 2, entitled: Influenza in the High-Risk Adult. I'm joined by Dr Rachael Lee, who's an Associate Professor of Medicine at the Division of Infectious Diseases at the University of Alabama in Birmingham, Alabama. Welcome Rachael.

Rachael A. Lee, MD: Thank you for having me.

Dr Pavia: Can you help us understand the burden of disease, particularly in higher risk adults from influenza?

Dr Lee: Yeah, I think it's helpful to start with an overall burden of influenza that we know for at least this past season. So, from October of 2021 through May of 2022, there have been anywhere from 7.4 million to 12 million flu illnesses. Now, these numbers are lower compared to years prior, but not as low as compared to last year. These have resulted in anywhere from 3.5 million to 5.6 million flu visits. And interestingly, most of these flu visits have actually been occurring between March and April of this year. From there, we've seen anywhere from 76,000 to 160,000 flu hospitalizations and anywhere from 4,700 to 14,000 flu deaths. So, those numbers overall are much lower compared to prior to COVID-19, but these numbers are starting to tick up again when we compare to the 2020 season.

Dr Pavia: I think most of us have some familiarity with the risk factors for severe disease, but can you go over them and give us some of that new information?

Dr Lee: Yeah. I like to put those who are at high risk for influenza-related complications into 3 specific buckets. So, I think by age, so elderly or very young, those with underlying chronic health conditions, or specific situations. And we'll elaborate a little bit further on these different groups.

So, for instance, those who are elderly, age over 65, are at high rate for having influenza-related complications and becoming hospitalized for influenza. And if you look at age less than 5, specifically ages less than 2, which would be kind of in your arena, those children are at high complications for influenza. And it's interesting when you look at the Centers for Disease Control and Prevention (CDC) data for United States last year, I think there were very few pediatric influenza deaths. And this year we had very few as well. I'd love to hear from your standpoint, what you've been seeing clinically.

Dr Pavia: We've seen a very unusual influenza season this year in children, where we had quite a bit of disease in November and December. And then when Omicron peaked, influenza dropped off substantially. Then it came back in February and it's really not gone away. We've seen influenza well into the early part of the summer. It's finally beginning to decrease and I think that's true for most more temperate areas. I don't know if it's the same in the warmer climate where you are.

Dr Lee: Yeah, I would agree. And in looking at the CDC influenza data, it looks like those numbers have peaked and are coming back down. Interestingly, those have all been influenza A, very few Influenza B cases this season.

So, when you think about underlying chronic health conditions, you can typically think about 2 different ways, so a condition that can become exacerbated by having influenza, such as asthma or kidney disease or liver disease, or you can think about those with weakened immune systems and may see higher complications from having influenza.

And then finally, when we think about special situations, people who are pregnant can have complications with their own health, but also complications with their baby. We can see higher rates of preterm birth and even stillbirth with that. And then also certain racial and ethnic minority groups have higher risks of complications. So, data from the CDC has shown disparities in hospitalization rates, admission to the intensive care unit, and in hospital death rates, specifically in non-Hispanic Black people, with a rate as high as 69 per 100,000, compared to white people where it's anywhere from around 30 to 38 per 100,000.

When we look at the burden of influenza in these high-risk groups, data from the 2020 influenza season saw 57% of hospitalizations were among those who are adults over the age of 65. 30 million had heart disease and are 6 times at increased risk of heart attack within 7 days of influenza infection. 39 million of these adults had asthma and/or chronic obstructive pulmonary disease (COPD) and that put them at greater risk of serious flu-related complications. And 34 million had diabetes and were 3 times more likely to be hospitalized and die from flu-related complications. And then lastly, 75% of flu-related deaths have occurred in adults of age over 65. And that was based on 2018 to 2019 season. Now, this data does look different since the COVID-19 pandemic, but we do still see complications of influenza, in addition to complications from COVID-19.

Dr Pavia: The complications of influenza are much broader than most people realize. Can you tell us a little bit about the direct and indirect complications?

Dr Lee: Yeah, that is a great question. I mean, if you look at just this most recent season, preliminarily, we've seen patients with hypertension, those with diabetes and obesity all have higher rates of being hospitalized for influenza.

And the way that I like to think about it is if you have influenza and you have a chronic condition such as COPD, that then can exacerbate that chronic disease. So, you may have COPD exacerbation, which then leads to going and frequenting the clinic, which then may lead to hospitalization. And then that can increase your frailty if you were hospitalized or in the intensive care unit, and that can increase your risk of mortality.

So, the direct effects or the things that we think about are the respiratory effects. So, you can think breathing problems, sinus infection, you can have bronchitis and pneumonia, whether it be directly from influenza, or you can have a secondary bacterial infection following your influenza infection. Or you can think about the more indirect effects which we see as infectious disease physicians, and those can be some sort of trigger of your exacerbation of renal disorder, diabetes. You can also see acute myocardial infarction and cerebrovascular disease. Rarely influenza can cause side effects like encephalitis or myocarditis, which we can see just rarely.

Dr Pavia: So, this helps us identify those patients that we see that are really at the highest risk of complications. And of course, we'd like to prevent disease in everyone, but how do we go about preventing and treating influenza in these most high-risk patients?

Dr Lee: Well, I think first and foremost, prevention is key and so anyone over the age of 6 months of age should get a flu vaccine every season with very rare exceptions. As an example, my son has an egg allergy and I know that people have probably heard that egg allergies, he should not get flu vaccine, but that has been disproven time and again, and I can say that my son has safely received his influenza vaccine every year. And really, if you think about timing, you want to be fully vaccinated before the influenza season starts. So, I typically recommend that people should be vaccinated by the end of October.

I think people have heard about the benefits of influenza vaccine, but to talk about it again, we know that even if there's not as high of a vaccine matching with the current strain, there has been data that has shown less severe influenza illness if you're fully vaccinated, fewer hospitalizations, reduced occurrence with heart attacks and strokes, and then preventing exacerbation of chronic health conditions, and finally reducing all-cause and influenza-associated mortality. When I talk to my patients, I think one of the hardest things to combat is saying, "Well, I got the flu, even though I got the flu vaccine, so what's the point?" And it really helps to have this data in your back pocket to tell people the benefits of getting vaccinated. And Andy, do you have similar stories with parents and children?

Dr Pavia: Yeah, I think it's even more difficult sometimes with parents of children because they're already getting a lot of vaccinations. And the tendency is to think of influenza as just another cold, which kids of course have many, many of. And you have to really talk about the potential that child's going to miss a week of school, that they may end up in the hospital, and they may even have more serious complications.

Dr Lee: If you look at the influenza vaccination coverage in adults through from 2010 to 2021, we've had a slow and steady increase, which I think is really good news overall, but we still have a long way to go. So, if you look at this data, you can see that young, healthy people are less likely to become vaccinated. Whereas people who are over the age of 65 have higher vaccination rates, which is really important. Interestingly, if you look at the data from children show the similar slide to this, in 2021, the data actually was reduced in terms of those receiving vaccines. And Andy, I don't know if you've seen kind of similar data in your institution, where people were probably not able to come to the doctor as frequently due to COVID restrictions or other things in that manner.

Dr Pavia: Yeah, we've certainly seen that locally. And just recently, there's been a piece in the New England Journal looking at vaccination rates and correlating it with COVID vaccination rates. And in the states where the lowest uptake of COVID vaccine, there's been a fairly large drop in influenza vaccine and much less so in the states where COVID vaccine has been readily accepted.

Dr Lee: Yeah. I mean, I hope that as we continue to learn more about effective ways to communicate vaccination with the COVID-19 vaccine, we can see improvement in influenza vaccination as well.

So, number 1, preventing with vaccination is very important. But what do you do when you have a patient that is presenting with signs concerning for influenza? And I think the key here is that we recommend antiviral treatment as soon as possible for any patient who is suspected or confirmed to have influenza if they're hospitalized, regardless of the timing, if they have some sort of severe or complicated or progressive illness, or they're at higher risk of influenza-related complications.

Typically, we say there's no need to wait for that confirmed influenza virus if you are suspecting influenza. So, I like to think about in terms of your positive predictive values, so if you're in a time when you're having a high amount of influenza during the season and someone presents with those symptoms, then you may want to consider starting that treatment while you're awaiting test results.

Dr Pavia: Rachael, many people have heard that antivirals are not as effective after 48 hours in adults who have uncomplicated influenza. What about patients who are at higher risk or hospitalized?

Dr Lee: I think that the data do support the use of those antiviral medications, particularly in people who are hospitalized. There's been pretty strong data that regardless of the timeframe between when your symptoms began and when you received those antiviral medications, if you were hospitalized, your risk of mortality is significantly reduced. So, in the hospitalized patient population, I would say, give it regardless. If they're presenting for an influenza illness, it's important to do our best to try to prevent those complications. Now, for those who are still in the outpatient setting, but may have risk factors for having influenza-related complications, I think that may be a more individualized approach depending on how the patient is feeling and their symptoms and whether or not you would do a risk benefit trying to treat them vs potentially holding it.

Dr Pavia: I think in writing the 2019 Infectious Diseases Society of America (IDSA) Guidelines, we tried to differentiate between those patients who should get treated and those patients who may want to choose to get treated. So, for outpatients, who didn't have risk factors and who were able to get treated within 48 hours, it's reasonable to offer them treatment because it can reduce the duration of illness and get them back to work more quickly. But for the groups you described to us, those at highest risk, those who are hospitalized, those with severe disease, it has potential to prevent hospitalizations and deaths. So, it's really a situation which you should treat and you should strongly make it possible for your patients to get treated in a timely manner.

Dr Lee: Right. I agree completely.

Dr Pavia: So, as infectious disease docs, we don't normally like to prescribe anything over the phone and do things before we have all the data in front of us on the actual diagnosis and susceptibility, is that the way we should think about influenza or should we get it started as soon as possible and we suspect it?

Dr Lee: Yeah, I think a hundred percent getting it started as soon as we possibly can. I think this is where we've really learned a lot about eMedicine and telehealth and how can we leverage that system to help prevent hospital-related complications in patients who are at high risk. So, in these settings, if a patient sounds like influenza and we're concerned about it and we can get them to get tested, we can also start therapy sooner rather than later, which will prevent downstream complications.

Dr Pavia: And I think another thing that we are able to do, particularly when we see patients who've had transplants, who are in the hospital with multiple complications, is we kind of prepare them for the fact that if they think they have influenza, they should contact their primary care physician or reach out to telehealth, but they should expect to get treatment if they have flu.

Dr Lee: Right. I agree.

Dr Pavia: We haven't really touched on antiviral drugs for prophylaxis and the indications are fairly limited, but when should we consider using antiviral drugs for prophylaxis?

Dr Lee: So, in my world, which I do infection prevention in a hospital, one of the biggest ways for chemoprophylaxis would be in a long-term care facility where you potentially are having an increased number of cases on a unit. I think the data has been very supportive of trying to prevent an outbreak when you give everybody chemoprophylaxis. There's also really strong data about chemoprophylaxis for patients that are at high risk for complications, say that they have a loved one at home that has influenza, you can give them chemoprophylaxis and that has been shown to help prevent having influenza later on.

Dr Pavia: Yeah. One of the pitfalls of prophylaxis is that we often don't get it started soon enough. And if there's been more than 48 hours since the exposure, they may be incubating disease already. So, in that case, it may make more sense to start presumptive treatment at full dose than to begin prophylaxis.

Dr Lee: Right. I agree.

Dr Pavia: Thank you, Rachael, for that really nice summary of influenza in high-risk patients.

Dr Lee: Thank you, and thank you for having me.

Segment 3

Andrew T. Pavia, MD, FAAP, FACP, FIDSA: Hello and welcome back. In this final segment, I'm joined by Dr Leigh Montejo, who's a family nurse practitioner and clinical assistant professor at Catholic University of America in Washington, DC. The title of this segment is Influenza and the Pediatric Population. Welcome, Leigh.

Is influenza really a big deal for children? Can you tell us about the burden and which children are at the greatest risk of complications?

Leigh Montejo, DNP, FNP-BC: Each year, influenza directly affects pediatric patients and their families. Millions are infected annually. Influenza accounts for many pediatric office visits, especially in children under 5 years old. And thousands of hospitalizations occur annually. Even death can occur in pediatric patients due to influenza.

This graph represents the number of influenza-associated pediatric hospitalizations during the 2019 season, which is more representative of the typical season. It's important to note that there's a significantly greater number of hospitalizations in pediatric patients ages 0 to 4.

This further illustrates that the highest rates of influenza associated hospitalizations occur in young children with rates decreasing with increasing age. The data provides strong support for the expanded use of influenza vaccines in young children, especially those less than 2 years of age.

While not common, influenza associated deaths can occur in the pediatric patient population. This graph represents the pediatric associated influenza deaths from 2018 to 2019 season through the 2021-2022 season.

Dr Pavia: We often think of diseases as icebergs with deaths being the very tip of the iceberg. What are some of the other serious complications of influenza in children that we should be aware of?

Dr Montejo: There are a number of complications associated with influenza that can affect pediatric patients. These include secondary infections, like pneumonia; infections in the sinuses and of the ears; dehydration; worsening of chronic medical conditions, like asthma or congenital heart disease; seizures and encephalopathy; inflammatory processes that affect the muscular and skeletal system and the heart, like myositis and myocarditis.

Of the already vulnerable pediatric population, certain children are at a greater risk for influenza complications. Those at a greater risk are children less than 6 months of age due to their inability of vaccines for this age group and their reliance on herd immunity through vaccination, especially from those who will be in close contact with them in the early months of their life; children 6 months old to 5 years of age; and children with underlying health conditions. Additionally, children aged 2 to 5 years old are more likely to present for medical visits to an ambulatory care urgent emerging care center, and children of American Indian and or Alaskan natives are more likely to develop severe illness that results in hospitalization or even death.

As we take a closer look at the 119 reported influenza associated pediatric deaths during the 2019-2020 season, we see that 44% occurred in children that were less than 5 years old, 6% in children that were less than 6 months old, 56% in children 5 to 17 years old. 43% of these children had a preexisting diagnosis and 22% had received an influenza vaccine.

Dr Pavia: Thanks, Leigh. I think it really emphasizes that children shouldn't be dying, and the 200 deaths is really 200 tragedies that we should be trying to prevent. It's also, I think really helpful the way you pointed out the groups that are greatest risk of dying, that include those with underlying conditions, like neurologic disease, and underserved groups. Tell us about how we can go about preventing these deaths.

Dr Montejo: The data on the burden of influenza for the pediatric population definitely indicates that there's a severity of burden. And it can vary as you mentioned, amongst individuals, and with the greatest risk being mortality. So, it is important to understand how the burden of influenza can be decreased for this vulnerable population.

Vaccination is the best protection against influenza. Everyone ages 6 months or older should receive the influenza immunization annually, except for in rare occasions based on individual circumstances and healthcare provider recommendations. It's important to note that egg allergies are not a contraindication for immunization, and there are egg-free options available. Vaccinations should occur as soon as the influenza immunization becomes available, ideally by the end of October, prior to the typical trends for illness to begin to peak in November. It is also important to note that vaccination can be co-administered with COVID-19 vaccines and all other pediatric vaccines.

During the 2019-2020 season, predominance of 2 anti-genetically drifted influenza viruses offered an opportunity to assess vaccine effectiveness against critical illness, life threatening influenza disease, and non-life-threatening influenza. Overall, vaccine effectiveness was 63% for all ages against critical illness when a child was fully vaccinated. Vaccine effectiveness was 75% against life threatening influenza and 57% against non-life-threatening influenza. A benefit of vaccination is a reduced risk of critical and life-threatening influenza illness.

From August 2010 through July 2014, 358 laboratory confirmed influenza associated pediatric deaths were reported among children aged 6 months to 17 years. Of these 358, vaccination status was determined for 219. Of these 219, only 75 or 26% had received the vaccine prior to the onset of their illness. While effectiveness can vary among season and virus type, strains and age, the overall effectiveness against death was 65%. A benefit of vaccination is a reduced risk of influenza associated pediatric death.

Dr Pavia: So, Leigh we're seeing an increased variety of influenza vaccine products, which I think can be confusing to some providers. Can you help us think about the different types of vaccines and how they compare?

Dr Montejo: Yes. Most influenza vaccines are formulated with non-live influenza virus. Of the non-live vaccines, there is a standard dose and a high dose formulation. The high dose vaccines are recommended for older adults and are egg based. The standard doses are used in all their populations, including pediatrics, and they are available in both in egg and an egg-free formulation. There are 4 egg-based vaccines and 2 non-egg-based vaccines. There is only 1 live influenza vaccine, which is administered intranasally.

Dr Pavia: You mentioned that you can co-administer influenza vaccines with the COVID vaccine, which is now very important since we're vaccinating down to 6 months of age. Are there any pediatric vaccines that would be a contraindication to getting an influenza vaccine at the same time?

Dr Montejo: It is safe to administer any annual influenza vaccine along with any other routine pediatric vaccines. This includes the COVID-19 vaccine, which can be administered at the same time as the influenza vaccine. We have seen that the flu and other viruses have started to spread alongside COVID-19 now that children are back in school, parents are working and people are resuming travel.

Dr Pavia: So, with all of the efforts to try and get immunization rates up for influenza in children and the disruption caused by the COVID pandemic, how are we doing? What does vaccine coverage look like for children?

Dr Montejo: That's a great question. I think it's important to evaluate how we are doing with vaccination coverage as a preventative strategy, since it is one of the most important strategies we have. You will see this graph depicts the coverage in the United States for the pediatric population by age during the last 11 seasons. The overall vaccination coverage for all ages averages about 66% over the past 11 seasons. The highest rate of coverage was during the 2019-2020 seasons. However, we have seen again, this decline as noted in the following seasons here. Overall, adolescents have the lowest vaccine coverage rate for all seasons.

Dr Pavia: It's kind of upsetting that we see the biggest drop occurring in the group 6 months to 4 years of age, who are the kids who have to come in for a lot of routine immunizations as well that are really important. And I think we know that a lot of that disruption has had to do with the COVID pandemic and with some of the vaccine hesitancy that's been drummed up over COVID vaccines. What are some of the strategies that you're using to help get immunization rates back up and overcome some of these barriers?

Dr Montejo: Yeah. So overall, we have seen influenza immunization uptake be very low in the pediatric population, and this is definitely something that needs to be improved. So, we look at different interventions that can help improve this through things like increasing access, through community flu vaccine events, providing retail pharmacies influenza vaccine and their ability to immunize pediatric patients, as well as school and clinic-based initiatives are important. Utilizing support staff and electronic health record alerts and encouraging compliance is also helpful. Offering incentives, gift cards, et cetera, can increase immunization rates as well. As you mentioned, decreasing disbelief in a vaccine efficacy through evidence supported education is very important and one of the strategies that we can use to help increase vaccine uptake in this population.

Dr Pavia: Some of my colleagues in primary care remarked that during the worst months of the pandemic, they just didn't have appointments for routine childhood immunizations. And now they actually have big blank spots in their schedules and they're actually having trouble getting kids to come back in for routine care. Are you seeing that?

Dr Montejo: Yes. We have seen a decrease in preventative health appointments, especially for pediatric patients who are otherwise healthy. There's been some belief that presenting for wellness visits or for vaccinations in a clinic where there are also sick children could potentially increase exposure to illness. We've also been seeing a lot of parents who had developed habits of wellness visits and annual visits. Those habits for the past 2 years have not been upheld and reestablishing those habits has been challenging for us. So, we are trying to maximize every opportunity that we see a patient to have the conversation about preventative health in that appointment. With the gaps in the schedule, we have a little bit more time so it has allowed us to have an opportunity to have these conversations. But we've always operated under the idea that a missed opportunity to talk about an immunization during a sick visit even is one that we don't want to miss.

So, we've still applying those principles to every practice. And we've really utilized our support staff and having those conversations with the parents prior to the provider even coming into the room. So, as we've really had a good outcome with having the education start with our own staff, and having buy-in in our own staff, and then our staff being able to then have the conversation with our patients, and then the provider coming back in and reiterating the conversation and addressing any hesitancy.

Dr Pavia: Yeah, it's such a great point. Educating people about vaccines is a process. It doesn't happen in the 5 minutes in one visit. Friend of mine used to say, "never miss an opportunity to vaccinate, never miss an opportunity to talk about vaccines."

Another thing, you mentioned the use of other settings for getting kids vaccinated. And I think initially primary care providers were reluctant to recommend vaccine away from the medical home because they couldn't track it and they didn't get that information. And I think in most states, the immunization information systems have really helped with that, because even if a flu vaccine dose or a COVID vaccine dose was given in a community event or in a pharmacy, it's now part of your ongoing medical record for that child and it's not such a disadvantage. Is that true for your practices as well?

Dr Montejo: Yes, I would say that was a huge strategy that has improved just the comfort of being able to deliver vaccines outside of the primary care pediatric setting, and being able to satisfy either, we talk about electronic medical record (EMR) alerts and being able to satisfy those other interventions. It's kind of all kind of flows in together. So yes, the universal, or it's state specific vaccine databases have tremendously helped. As well as there was some hesitancy in parents even presenting to outpatient settings. They didn't think the information would get to the schools or would be counted. So, with having a universal way or a state-based way of tracking those immunizations has really been helpful.

Dr Pavia: Yeah. I think pretty much all of the pharmacies that participate in vaccination use the immunization information systems, and many health-department sponsored events also do that. So that's been really helpful.

Let's turn briefly to antiviral drugs. We're really focused on vaccines, which is our number 1 tool. But when influenza actually does happen, can you just briefly remind us about antiviral drugs and how we can use them?

Dr Montejo: Yeah. So, the importance of prevention with immunization is definitely key, but things do happen and disease does occur. And I think the most important thing to remember with any antiviral treatment is the recommendation is to administer this as soon as possible to patients who have suspected or confirmed illness, especially those who are hospitalized; or at risk for complications; or have severe, complicated, or progressive illness. The greatest clinical benefit is achieved when the antiviral therapy is started within 48 hours of the symptom onset. However, children at high risk for complications can still benefit from antiviral therapy that is started after 2 days of symptoms onset. And this should be considered as a treatment option for these high-risk children in this population.

Dr Pavia: And what drugs do we have that are currently approved for use in children? And what ages are they available for?

Dr Montejo: So, there are 2 oral and 1 inhaled antiviral medication that can be used in treatment or chemoprophylaxis, and 1 IV medication that is used only for treatment in pediatric patients. Oseltamivir is an oral medication that can be used to treat patients at any age, and it can be used in chemoprophylaxis at age 3 months or older. Baloxavir is another oral medication that can be used to treat and used for post-exposure chemoprophylaxis in patients 12 years and older. Zanamivir is an inhaled medication that can be used to treat patients 7 years old and older, and for chemoprophylaxis in patients age 5 and older. Because this medication is administered through inhalation, it is not recommended for patients with underlying air disease, such as asthma. Peramivir is administered IV for treatment and it is not recommended for chemoprophylactic use.

Routine use of chemoprophylaxis is generally not recommended pre- or post-exposure. However, it can be considered in patients 3 months of age and older, pre- or post- who are at very high risk for developing influenza associated complications and who have not received influenza immunization due to these contraindications. Chemoprophylaxis was fully covered in the first segment of this presentation.

Dr Pavia: Leigh, thank you for that great discussion, very comprehensive review of disease in children. It's been really helpful.

Dr Montejo: Yes. Thank you for having me present on this very important topic.

Dr Pavia: So, I hope that you found these 3 sections helpful. We are going to in all likelihoods, see a fair bit of influenza this coming winter. We're going to have to deal with it against the background of continuing infections with SARS-CoV-2. And knowledge is power so I hope we've empowered you to treat this viral infection as well as COVID 19, which has occupied so much of our attention for the last 2 and a half years.

I want to thank Mike, Rachael and Leigh for joining me on this program and for a really great discussion. And thank you for participating in this activity. We hope you found this information valuable.

This is a verbatim transcript and has not been copyedited.