2018-2019 Recommendations for Influenza Prevention and Treatment in Children: An Update for Pediatric Providers

Moderator: Ibad Khan

Presenters: Lisa Grohskopf MD, MPH; Flor Munoz, MD, MSc, FAAP

Date/Time: September 27, 2018, 2:00 – 3:00 pm ET

Ibad Khan:

Good afternoon. I’m Dr. Ibad Khan and I am representing Clinicians Outreach and Communication Activity, COCA, with the Emergency Risk Communication Branch at the Centers for Disease Control and Prevention. I would like to welcome you to today’s COCA Call: 2018-2019 Recommendations for Influenza Prevention and Treatment in Children: An Update for Pediatric Providers.

You may participate in today’s presentation via webinar or you may download the slides if you are unable to access the webinar. The PowerPoint slides and the webinar link can be found on our COCA webpage at emergency.cdc.gov/coca. Again, the web address is emergency.cdc.gov/coca. Free continuing education is offered for this webinar. Instructions on how to earn continuing education will be provided at the end of the call. In compliance with continuing education requirements CDC, our planners, our presenters, and their spouses/ partners wish to disclose they have to financial interest or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters.

Planners have reviewed content to ensure that there is no bias. Content will not include any discussion of the unlabeled use of a product or a product under investigational use. Except Dr. Lisa Grohskopf would like to disclose that ACIP recommends that people with egg allergies should receive the influenza vaccine even though an egg allergy is a labeled contraindication for most influenza vaccines. Dr. Flor Munoz would like to disclose that the use of influenza antivirals in hospitalized, severely ill patients is off label, and the use of influenza vaccines in pregnant women is off label. However, these are recommended by CDC and AAP. CDC did not accept commercial support for this continuing education activity.

After the speakers have presented, you will have the opportunity to ask questions. You may submit questions at any time through the webinar system by clicking the Q&A button at the bottom of your screen and then typing your question. For those who may have media questions, please contact CDC Media Relations at 404-639-3286, or send an email to media@cdc.gov. If you are a patient please refer to your questions to your healthcare provider.

At the conclusion of the session, the participants will be able to accomplish the following. Summarize data from the 2017-2018 US influenza season and the 2018 Southern Hemisphere season to inform about preparations for the 2018-2019 US influenza season. List key recommendations in the AAP influenza policy statement, “Recommendations for Prevention and Control of Influenza in Children, 2018–2019” and in the CDC Advisory Committee on Immunization Practices document, “Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2018-2019 Influenza Season.” Outline background information about updated recommendations for the use of intranasal live attenuated influenza vaccine (LAIV4) in children. And finally, list recommendations for influenza antiviral use in children.

We would now like to welcome our two presenters, Dr. Lisa Grohskopf and Dr. Flor Munoz. Dr. Grohskopf is a Medical Officer in the Influenza Division at the Centers for Disease Control Prevention and works in influenza vaccine policy development and also serves as lead of the ACIP Influenza Work Group. Dr. Munoz is a pediatric infectious disease specialist at Texas Children’s Hospital in Houston. She is also a member of the Committee on Infectious Diseases of the American Academy of Pediatrics as well as a representative in the Committee on Infectious Diseases on the Influenza Working Group of ACIP. Thank you to both of you for joining us today. Dr. Grohskopf, you may begin with your presentation.


Lisa Grohskopf:

Thanks very much. I’m going to present three parts in this presentation. One, a brief overview of surveillance mostly from last season, a little bit of information on the influenza antiviral medication recommendations, and an update on the ACIP influenza recommendations for 2018-19.

First, with regard to surveillance, a quick review of last season. As most people know, last season was a high-severity influenza season with high levels of outpatient clinic and emergency department visits for influenza-like illness, a high degree of influenza-related hospitalization rates, and elevated and geographically widespread activity across the country for an extended period of time. Activity began increasing in November and reached an extended period of high activity during January and February. Overall, influenza A (H3N2) viruses predominated for the season. Influenza B viruses began to be reported more frequently than influenza A viruses from about early March until mid-June. The majority of circulating viruses were similar to the cell-grown reference viruses that were present in the 2017-18 influenza vaccine. Next slide.

So we have some surveillance slides coming up next, some graphics. This is data from the CDC Influenza-like Illness Network or ILI.net which is in this slide comparing data from several seasons. Each season is represented by a different line. The lines summarize five different seasons prior to the 2017-18 season and on the Y axis, we have the percent of illnesses or the percent of visits that were due to ILI and then on the X axis, we have calendar week. The most recent season, 2017-18, is in the red line with the triangles. We can see that for last season, ILI was associated with a high proportion of visits reported to this network and the peak actually that you can see around week 4 or 6 in the calendar is actually almost as high as that for the 2009 pandemic which is the gray line, that’s the peak all the way off to the left of the graph. Moreover, it’s higher – that peak – than all of the other seasons that are pictured. Next slide.

These bar graphs provide some insight into the types of virus that were circulating last season. These are the results of influenza-positive tests reported to CDC by US clinical and public health laboratories. The clinical labs are up on the top graph, the public health labs on the bottom graph. The clinical laboratories don’t often – many of them don’t subtype out flu A and flu B so we have basically two classes here just all A, all B for the most part with the A’s in the yellow and the B’s in green. You can see overall, we have a predominance of influenza A and as mentioned earlier, we do begin to see an increase in B later in the season with a later peak of B. If we go to the public health laboratories, by and large, these laboratories do subtype out A viruses and conduct lineage testing on B viruses. You can see overall, our predominance is in the red there which are the H3N2 viruses. We do have some H1N1 in orange but much less. Next slide.

This is lab-confirmed influenza-associated hospitalizations, so the last line graphed two slides ago was outpatient visits. This is hospitalizations and this comes from the surveillance system Fluserve.net. These data are presented cumulatively so we still have on the X axis the MMWR calendar week and we have on the Y axis rates per 100,000 population for hospitalization and because these are cumulative rates, we expect that the curve is going to go up as we move from the left to the right across the graph. The most recent season, 17-18, is that sort of pale green line that’s up at the top with the very highest hospitalization rates. For 2017-18, the cumulative rate was 104.9 per 100,000 which is far higher than its next highest neighbor which was the 2014-15 season at 64.2 per 100,000. Next slide.

These two slides summarize two different types of mortality data and on the left, we have pneumonia and influenza mortality. This is from the National Center for Health Statistics. These are not laboratory-confirmed influenza cases but these are data that come largely from death certificates and it’s basically the percent of all deaths reported that were reportedly due to PNI or pneumonia and influenza, again not confirmed flu cases and there are multiple seasons. Actually, pretty much each red peak that you see in that graph represents a season. The most recent season 17-18 is the one on the right-most side of the graph. We see the peak is similar in magnitude to that of our most recent severe season prior to that which was the 2014-15 season which is the second peak from the left. Now, in contrast to the National Center for Health Statistics data, on the right we have the pediatric mortality data. The deaths of children that are associated with confirmed influenza have been reportable since 2004 so this is one instance where we get actual mortality data that’s confirmed due to influenza. For 2017-18, we unfortunately have a total thus far of 180 pediatric deaths which is higher than the previous three seasons. Next slide.

This is a slide that attempts to summarize some results from a severity index which takes into consideration outpatient visits, hospitalizations, and deaths and here we have seasons from 2009-10 so that the pandemic season, when H1N1 pdm09 first emerged all the way up through 2017-18, the most recent season. One notable thing about our past season was that this was the first season where the index met high severity criteria for all three age groups. You can see, in each cluster of bars, we have a light blue bar that’s all age groups and then we have them broken down by category in the next three bars – children, adults, and older adults, so this just sort of points out the severity of the season across the age spectrum. Next slide.

This is the last surveillance slide and it’s a little busy but we just wanted to give you a little bit of an impression of what’s been going on in the Southern Hemisphere. This slide has data similar to the bar graph that we saw earlier but this is for various regions in the Southern Hemisphere and broken down by season with the summer 2018 Southern Hemisphere season all the way off to the right. We can see that the picture isn’t the same as we move from region to region. We have some areas where H1N1 – those are again the orange viruses predominate. We have actually some where there’s a little bit more of a presence of that blue/green which is H3N2. The peaks are in different places. We don’t see the same thing everywhere and by extension, just something important to note is that we really can’t predict what we’re going to see in the Northern Hemisphere in terms of necessarily what viruses we’re going to see predominate, how similar they’re going to be to vaccine, what the E is going to be, how severity is going to be. We really can’t predict what’s going to happen here based on what happened in the preceding summer Southern Hemisphere season. Next slide.

Just last little bit, winding up for surveillance, these are just a couple of links for additional sources of surveillance data going forward for 2018-19. Typically beginning in October, we start to have more detailed reports as the US influenza activity typically then begins to pick up on FluView so that’s something to watch. We have a static report that will come out weekly as well as FluView Interactive which is an online application where you can get some data and break it down according to different seasons or different age groups. Next slide.

Okay, moving on to antiviral treatment recommendations. There’s not a great deal new here and I know also, Dr. Munoz will be covering this as well but just some reminders that antiviral treatment is recommended as early as possible for any patient with confirmed or suspected influenza who is hospitalized, has severe complicated or progressive illness, or is at high risk for influenza complication. Next slide.

Just a reminder of folks who are considered to be at high risk and for whom antiviral treatment is recommended. Children under 2 years old. Really, all children under 5 years old are considered at high risk for complications from flu but the risk is particularly high in those under 2. Adults 65 years of age and older, pregnant and postpartum women, children under 18 receiving long-term aspirin therapy or really any therapy with aspirin or salicylate-containing medications, American Indians and Alaska natives, those with underlying medical conditions, and residents of nursing homes and chronic care facilities. I kept some adult material here because my understanding is, at least for vaccines, maybe not so much for antivirals – some adults are vaccinated in provider offices but we’ll focus on the pediatrics mostly. Next slide.

In addition to the folks mentioned in the slide before last, those for whom antiviral treatment is recommended who you see here again in the first bullet in this slide. There are also groups of folks for whom antiviral treatment can be considered and not necessarily recommended but based on clinical judgments, it can be considered and those are basically for any previously healthy symptomatic outpatient who is not necessarily at high risk who has confirmed or suspected influenza on the basis of clinical judgment if the treatment can be initiated within 48 hours of illness onset. The clinical benefit is greatest for everybody when antiviral treatment is initiated early. For the current period of time, we have three FDA-approved antivirals that are recommended for use in the US. These are all neuraminidase inhibitors – oral oseltamivir, inhaled zanamivir, and intravenous peramivir. Next slide.

Brief mention of potentially a new antiviral that you may hear about sometime in the next year – Baloxavir which targets a polymerase in the virus. This is a new and different mechanism of action from the previous drugs that we’ve had at our disposal. It’s given orally in a single dose and the application is for treatment of acute uncomplicated influenza in patients ages 12-64 years. In preclinical studies, it’s been noted to be associated with shorter time to alleviation of symptoms than placebo and more rapid declines in infectious viral load; however, there has been emergence of viral escape mutants noted that have reduced susceptibility so that will be something to keep an eye out for once this drug gets approved. Okay, next slide.

Lastly, update on the ACIP recommendations for influenza vaccination for 2018-19. Next slide?

Again, you’ll see some mention of adults in here but we’ll focus on the kids. Groups recommended for vaccination – nothing’s really changed here. Routine annual influenza vaccination is recommended for all persons greater than or equal to 6 months of age who don’t have contraindications. While vaccination is recommended for everyone in this age group, there are some for whom it’s particularly important including those 6 months and older who are at increased risk of complications and severe illness due to flu which we’ll go over in the next slide, sort of our high-risk groups. Contacts and caregivers of persons under 5 years of age and those over 50 years of age and also contacts and caregivers of people with medical complications that put them at higher risk for severe complications from flu and those folks are summarized on the next slide.

This looks somewhat similar to the one for high-risk groups for antiviral treatment. Again, children 6-59 months and adults greater than or equal to 50 years, those would be folks that are high risk and should be prioritized for vaccination. Of note, also, children under 6 months old. Those tiny babies are still at high risk but we can’t vaccinate them yet because we actually don’t have a licensed vaccine for that age category. It’s very important for that group to vaccinate contacts and caregivers. Also, persons with chronic pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic, or metabolic disorders. Immunosuppressed persons, women who are or will be pregnant during the influenza season, children and adolescents who are receiving aspirin or salicylate-containing medications, residents of nursing homes and long-term care facilities, American Indians and Alaska natives, and persons who are extremely obese, specifically those with a BMI of 40 or higher. Next slide.

Quick overview of the updates for this season. We sort of have four categories of changes to the ACIP guidance for the season coming up. As usual, we have an update in the strain composition of the vaccine for 2018-19. Next, we have the reintroduction of LAIV4 as an option for vaccination for the season. We have a very small update in vaccines for egg-allergic persons and two labeling changes for existing vaccines. Next slide.

First, I won’t spend too much time on this, the 2018-19 vaccine composition. For trivalent vaccines, we have an A/Michigan/45/2015 (H1N1) pdm09 and A/Singapore/INFIMH-16-0019/2016 (H3N2). This is an updated H3N2 from last year and a B/Colorado/06/2017-like Victoria lineage virus which is also an update from last year. So many of you I’m sure remember, for trivalent vaccines, we have three influenza viruses represented. They’ll be an H1N1, an H3N2, and one B. B viruses come from two different lineages and in the trivalent vaccine, only one of those is represented. There was a Victoria lineage virus last year as well but it’s just been changed slightly for this year. Quadrivalent vaccines which it’s anticipated will be most of the doses available for this season. Over time, we’ve had a decrease in the number of trivalent doses available as the quadrivalent has become more common. The quadrivalent vaccines will contain the above three viruses but also a Yamagata lineage B virus which is B/Phuket/3073/2013 which was also the Yamagata lineage virus that was in the quadrivalent vaccines last season. Next slide.

This is the second change which is a somewhat larger one. We have ACIP recommendations for the use of LAIV4 for 2018-19. As you know, LAIV was not recommended for any population during 2016-17 or 2017-18 largely due to concerns about low effectiveness of the vaccine against the influenza A H1N1pdm09 viruses among children 2-17 years of age that was noted during the 13-14 and 15-16 seasons. This after some study is thought to be due to poor fitness of the H1N1pdm09 virus that was contained in the vaccine during those periods. In February 2018, ACIP reviewed some additional data in basically three categories of data, two of which were pooled analyses of previous seasons’ data primarily from observational studies and also some manufacturer data on shedding immunogenicity of a new H1N1pdm09 vaccine virus which exhibits some improved replicated fitness compared with previous H1N1 vaccine viruses. As a result of this, for 2018-19, LAIV4 is again an option for those for whom it is appropriate. Importantly, we do not yet have any U.S. VE data on the new formulation with the H1N1pdm09. The manufacturer data was not efficacy data so it remains to be seen how well the vaccine will work for that particular virus. Next slide.

Just to follow up a little bit on that. We do have a bit of a difference between ACIP and the AAP recommendations in that ACIP makes no preferential recommendations for one vaccine type over another where more than one is appropriate and available for any given recipient. AAP currently recommends IIV as the primary choice for children. I just feel it’s important to point out that the recommendations share the same principle that influenza is a problem for kids. It’s an important source of morbidity and mortality burden for children. Vaccination is an important preventive strategy and both encourage that. Next slide.

Very brief reminder and it’s getting close to time so I won’t spend too much time on it but because we didn’t have LAIV recommended for the last couple of years, I just want to remind folks that the contraindications and precautions list is a bit longer for the LAIV than it is for the inactivated vaccine. Nothing has changed here. Nothing has been added in terms of contraindications and precautions. It’s just a bit more long of list than there is for IIV. We have three categories of people who shouldn’t receive IIV, those who are on the first bullet outside of the licensed age indication, under 2 or over 49 years old. Those that have labeled contraindications in the package insert which would be history of severe allergic reaction to any vaccine component. Now, I’m going to say one thing and this is noted in the preface. That includes egg in the package insert because it’s an egg-based vaccine LAIV. Note, however, that ACIP makes one exception with regard to the history of severe allergic reaction language in the package insert in that ACIP does recommend vaccination for persons with egg allergy of any severity. The other one would be concomitant aspirin or salicylate medicine-containing therapy for children and adolescents. In addition, ACIP also recommends – these aren’t labeled contraindications but ACIP recommends LAIV not be used in pregnancy, immunocompromised persons, children under 5 with a history of asthma or wheezing, caregivers or contacts of persons requiring a protected environment so really the most severely profoundly of the immunosuppressed and persons who have received influenza antivirals within the previous 48 hours. Next slide.

Precautions for the use of LAIV. Two of them are pretty similar to the ones we see with all the other influenza vaccines, moderate or severe illness with or without fever, Guillain-Barre syndrome within 6 weeks following a previous dose. There are a couple of precautions specific to LAIV which include asthma in persons 5 and older and other medical conditions from the list we’ve already reviewed that predispose to increased risk of severe influenza illness. Next slide.

For egg allergy, the main change here is that LAIV is an option for persons with a history of egg allergy this year. That was actually approved by the ACIP in 2016 before it was recommended that LAIV not be used for the following season so this is really the only change here. I just want to point out again that ACIP recommends that people with egg allergy of any severity should be vaccinated and again, this is a difference from the FDA-approved labeling for most inactivated vaccines and also for LAIV in which severe egg allergy is a contraindication. Most of them read severe hypersensitivity reaction to the vaccine or any component including egg so this is something where the ACIP recommendations depart from package labeling. Next slide.

Two licensure changes very quickly. We had in the last year two vaccines already approved that basically just had expansions in their age indications that they’re licensed for. Afluria quadrivalent was 18 and older, now it’s 5 and older since last August 2017. Fluarix was originally 3 years and older, now it’s 6 months and older so for the 6- through 35-month-old children, we now have a total of three inactivated vaccines that are licensed. Of note, the dose volume for Fluarix like FluLaval for this age group is the same dose everybody else gets, 0.5 mL. Next slide.

Now, this can potentially make for some confusion. As I said, we now have three licensed products for this age group at least in terms of the inactivated vaccines. We have Fluarix and FluLaval which are 0.5 mL dose and we have Fluzone which is still a 0.025 mL dose so one potential point of confusion is just know what you have on hand and what the appropriate dose is. Another thing that we got questions about last season was dose volume versus number of doses. We did get questions about if a child got FluLaval quadrivalent which was licensed last season at a 0.05 mL dose but they were one of those kids, say they’re a first-time vaccinee who is a year old and they need two doses – do they still need two doses if they got 0.05 mL of FluLuval and the answer is yes because the dose volume is distinct from the number of doses so that child still needs a second dose of vaccine at least 4 weeks later. Next slide?

I think this is close to my last one. So this is just the algorithm for determining the number of doses needed for those 6 months through 8 years old. This approach is the same as last season and I believe the season before. It is essentially if the child received at least two total doses of trivalent or quadrivalent vaccine prior to July 1, 2018, they need only one dose for 2018-19. If that isn’t the case, if they’ve not gotten any doses or only one dose or if you don’t know what their vaccination history is, they would need two doses administered at least 4 weeks apart. Next slide.

This is just a page with some links to additional resources. We have information on surveillance, vaccination coverage, information for healthcare professionals as well as the general public, and the last one is actually an activity book for children which the cover is pictured off to the side there. Next slide?

Thank you very much for your attention. I know that was kind of quick. I’d like to now turn it over to Dr. Munoz.


Flor Munoz:

Thank you very much, Lisa, and thank you everyone for the opportunity to be here with you this morning. My presentation is going to focus a little bit more on the AAP recommendations for 2018-2019 for influenza prevention and treatment in children and with that in mind, just to give you a quick review about the Committee on Infectious Diseases and the American Academy of Pediatrics recommendations. COID is in charge of reviewing any information regarding influenza including epidemiology, vaccines and antivirals, and providing recommendations for the prevention, treatment, and diagnosis of influenza in children and this process happens every year and is updated similar to what happens with ACIP and there is participation of various committees, councils, sections, and even the AAP board into these recommendations. The information is available in the red book but also on line through the different venues as you can see. The recommendations for influenza prevention for 2018-19 from the AAP as you will see are aligned with those of the CDC and ACIP because, indeed, we rely heavily on the information that is collected by the CDC and their recommendations to be able to put together recommendations specifically for children. As you have heard, the one difference with the recommendations this year is that the inactivated vaccine is recommended by the AAP as a primary choice for children this season with LAIV being an option for those who would not otherwise receive the inactivated vaccine. The recommendations this year also affirm the vaccination for egg-allergic patients as was previously discussed and then we do have brief updates regarding the recommendations for treatment with antivirals as well, so I will go over those today.

As you can see and as was mentioned by Dr. Grohskopf, the most important message that we want everyone to take from this presentation is that everyone should be vaccinated against influenza starting at 6 months of age and this is the main recommendation which is a universal vaccine recommendation in the United States. The populations that are at particular risk as were described before include, of course, the children less than 5 years of age, those over 65, and certainly pregnant women and I would like to point out to your attention here the fact that in addition to those with underlying medical conditions as listed here, we do have to keep in consideration that anyone in contact with these individuals in these four groups – so children, persons over 65, pregnant woman, and those with underlying conditions should also be vaccinated in order to provide protection to them so it’s healthcare personnel and also household contacts of these individuals.

The recommendations differed a little bit this year as you know and this is the wording that was included in the AAP and just to give you a little bit of background about this particular recommendation, during the routine meeting in April of the Committee of Infectious Diseases, the information that was available to that date regarding LAIV and IIV effectiveness was reviewed and as you can see, the AAP recommends that it is an inactivated influenza vaccine either trivalent or quadrivalent that is used as a primary choice for influenza vaccination in children because with that information available at the time, we data about the effectiveness of the LAIV4 being inferior in the previous seasons and no data for effectiveness for the current formulation of LAIV4. However, the AAP indicates that quadrivalent live attenuated vaccine could be used for children who would not otherwise receive influenza vaccine, specifically those who might refuse the inactivated vaccines or the shot and it has to be for children who are age appropriate as recommended for 2 years and over and who are otherwise healthy without underlying medical conditions.

The rationale for the recommendations was based on the same literature that was reviewed by both ACIP and AAP and I just wanted to point you to these two publications, one MMWR. The main author is Dr. Grohskopf and then in AAP News that goes over the rationale of why these recommendations were put into place and what you will see as it was mentioned before is that the data that was reviewed by both AAP and the ACIP was similar in the sense that we both looked at observational studies that had pooled data analysis for the effectiveness of LAIV and IIV for previous seasons including 2013-14 to 2015-16 in children specifically. Also, meta-analysis that looked at all published literature for the 2010 to 2016 seasons for both types of vaccines including in this case LAIV3 and LAIV4 and then the study conducted by the manufacturer that Dr. Grohskopf mentioned as well where it was not an efficacy study but it was a study looking at what is the best strain to utilize in the vaccine to be able to improve the immunogenicity of the vaccine and with that information, these were some of the observations from those studies. When you look specifically at the A(H1/N1) efficacy for those studies, depending on the source, it was noted that the LAIV was better than no vaccination for children 2-17 years old but in the meta-analysis, this was true only for the non-US studies. The IIV was better than LAIV for all age groups in the United States and when you look at the formulation of LAIV4 with the new A/Slovenia strain that was selected, this information is important because this vaccine has been used already in the previous season 2017-18 in the UK, Finland, and Canada but we have no data for the United States yet as was mentioned with this particular strain. It is expected that information regarding its effectiveness will be available and that, of course, this will inform future recommendations. In these analyses, the effectiveness for H3N2 was similar of LAIV and IIV and also for B strains, you can see that LAIV actually had some advantage with better effectiveness.

Now, I wanted to also mention a couple of other recommendations that became available so for example, for ACOG which is obstetrics and gynecology, at the same time in April, they were reviewing similar data and you can see how for ACOG whose role is to give recommendations for pre-pregnancy, pregnancy, and postpartum, they consider influenza vaccination as an essential element of prenatal care and postpartum care as well and they have no particular preference. Basically, any of the licensed recommended age-appropriate inactivated influenza vaccines could be given during pregnancy.

In other updates, in terms of other recommendations, you might have seen the American Academy of Family Practitioners’ recommendations that came up in July where their recommendation is similar to that of the AAP with the preferential recommendation for IV for 2018-19.

So I think that in general, again, most important message that we would like to give is that universal influenza immunization is recommended annually but all the organizations, that IIV or LAIV can be used during this season. The AAP has no preference for trivalent or quadrivalent vaccine and certainly, when using LAIV, it has to be based on the specific recommendations for age and also for health status. Dr. Grohskopf already went in detail through the contraindications and precautions but these are based on the different vaccines related to either severe allergic reactions for contraindications or precautions as mentioned with acute febrile illnesses or history of Guillain-Barre syndrome.

This is just a table from actually the MMWR that goes into detail if you want to use it as a resource for the different types of vaccines indicating what would be contraindications and what would be the precautions for the use of these vaccines.

Now, the AAP also has a statement regarding the number of seasonal influenza doses that are given to children 6 months to 8 years of age. Remember that in this age group, two doses of vaccine are necessary to achieve good immunogenicity when children are receiving the vaccine for the first time or if they haven’t received at least two doses of an influenza vaccine before the start of this season and this is well established. After two doses, you will be able to get adequate immunity for the season and the reason this is relevant to us as well is because we want to make sure that these young children are fully vaccinated before influenza starts circulating.

We get asked often when is it too early to give the flu vaccine because as you know, we would like to make sure that all children especially are fully vaccinated by the time influenza starts circulating and because influenza circulation is unpredictable, we’ve had seasons where we have already influenza in October, sometimes December, sometimes after the new year but because of that, the recommendation from AAP is that complete vaccination should be achieved if possible by the end of October and that means that we need to keep in mind some programmatic issues to make sure that those who need two doses have those two doses before the end of October. It is important to keep in mind that even if you’re not able to get to that goal of continuing vaccination, offering the vaccine throughout the season is critical because you can have protection for more than one strain and you also can have different exposures during the season.

This question about waning immunity has also been addressed in recent studies and so it is expected that the antibody levels will decay naturally after vaccination and this usually starts approximately after two months from the vaccination but the waning immunity has been reported mostly in adults, especially elderly adults, and even though it happens naturally again in anybody that is vaccinated, in pediatrics, these waning antibodies have now been associated with increased risk of disease. Therefore, again, start vaccinating if you have influenza vaccine already available. There should be enough protection afforded by those vaccines for the next six months which is when we expect to see influenza.

Now, these are additional recommendations that the AAP has as well in terms of ways to potentially improve uptake of influenza vaccine in your office by making it accessible for all children, making sure that you let your families know that the vaccine is available, either have a set of vaccination clinics or allow individuals to come in to receive their vaccine, provide available hours, and any opportunity such as well-child checks including actually patients who might be in the hospital who don’t have other contraindications for influenza vaccination could be offered vaccine prior to discharge, particularly when their reason for admission is not something that affects their immune system. Other options to improve coverage include the use of standing orders, making sure that all family members are covered to protect, especially those younger children who might not be able to receive vaccine, being able to work with any venues where families receive the vaccine to document that you have those patients receiving their vaccination and that should be clear in their medical records, and then, of course, making sure that all contacts and healthcare personnel are vaccinated in your practice.

The egg allergy recommendations have already been discussed and this is just a brief summary indicating that we now know that egg allergy does not increase the risk of anaphylactic reactions in individuals who have egg allergies or history of it and, therefore, any licensed recommended influenza vaccine could be given to them without special precautions other than those recommended for routine vaccines.

I am going to give you just a couple of pointers regarding diagnosis and then we’ll talk about treatment but basically, the diagnosis of influenza as you know is most reliable when you use molecular detection assays so PCR-based laboratory confirmation is the most accurate. We have as you know available many new options right now for CLIA-certified point of care rapid diagnostic testing and certainly, in large institutions and hospitals, PCR seems to be the main method of diagnosis but it is important to consider when influenza is already circulating in your community to be able to start testing or start considering influenza, especially when you’re relying on a clinical diagnosis which can be made as well of course.

This is just a table to have as a reference of different diagnostic tests and, again, the fact that with the rapid molecular assays, you are able to have a diagnosis rather promptly within 20 or 30 minutes and that you are able to detect both influenza A and influenza B. I’m not going to spend much time on that.

A couple of points regarding the clinical presentation of influenza in children to remind you that children might be a little bit different from adults in the sense that they do have usually a febrile illness but they have also more respiratory symptoms that could be consistent with any other respiratory virus illness and they could have also gastrointestinal symptoms so a little bit more varied presentation.

Nevertheless, it is different from a cold because, indeed, for most flu cases, you will have more systemic symptoms including body aches, headaches, malaise, and irritability in the very young children and then we need to make sure that it is clear for families that a cold is different from the flu because the flu does have potential consequences that can result in hospitalization and we can actually prevent them by using vaccination and also there are diagnostics and treatments available.

The different complications that we need to keep an eye on for this season include just the fact that influenza in and of itself can cause pneumonia. It can be associated with a secondary bacterial infection as well and that you have other complications such as myositis, otitis, myocarditis, also encephalopathy and different types of manifestations such as febrile seizures that can occur. Young babies can present with a sepsis-like syndrome or just high fever and teenagers and other children can have exacerbation of asthma so certainly, all of these are important to keep in mind during the flu season. Among the complications that we see in children, the youngest as was mentioned before, especially those under 5 are going to be more likely to have these complications and require medical attention and that is true, especially for those under 2 years who are more likely to be hospitalized. Keep in mind that in the United States, it’s going to be approximately 1% of those children who have influenza illness that will be hospitalized and the mortality that we have seen tends to be associated in many cases with some of these secondary bacterial infections but also it could be associated with complications of influenza itself.

Dr. Grohskopf showed you this slide already where you see the mortality and how we had a very severe season last year so it’s important to keep in mind that this is the reported cases; there could potentially be more cases out there.

When you look at the cases of mortality last year, the main age of these children was 7 years and you can see how it could be young babies a couple of months of age to teenagers 17 years of age that were affected by influenza. Most of those children that died from influenza last year had to be hospitalized and you see how an important point here is that almost half of them, so 49% did not have any high-risk conditions that were recognizable and were previously healthy when they were affected by the flu. Similarly, the majority, nearly 80% were not vaccinated and this is a reminder about the fact that we do need to vaccinate and that we need to cover all children.

I do want to mention that when we do have to answer questions from families about the effectiveness of the vaccine, we do need to keep in mind that there could be an effect of the vaccination against the severe complications of influenza. There are at least two studies that are important to have in your files. One is by Jill Ferdinands from the CDC who looked at ICU hospitalizations to see what the effect of vaccination could be in preventing these most severe cases that require hospitalization in the intensive care unit and in this study, vaccinated children were either 74% to 82% less likely to be admitted to the ICU for influenza versus other children who were not vaccinated that were either in the ICU or community controls and then Brendan Flannery, also from CDC, looked at the effect of vaccination against death. Again, in children in looking at those who were vaccinated versus not vaccinated, those who were vaccinated were 65% less likely to be die of influenza so protection that is higher potentially than just the general effectiveness that you see for acquiring influenza illness, so keep that in mind.

Finally, I will not go into a lot of detail on this because Dr. Grohskopf already mentioned to you but the recommendations for treatment of influenza in children from the AAP are in line with those of the ACIP and important to know that treatment of influenza does not require laboratory confirmation. You would be able to start treatment based on clinical suspicion and so we would like to make sure that especially for those children who are hospitalized, those that have severe or progressive influenza, or that have high-risk conditions that increase their chance for complications are offered antiviral treatment as soon as possible and that you consider treatment as we saw in the recommendations any child with suspected influenza and especially those who live with persons of high risk. Ideally, the treatment should be started within 48 hours of onset of symptoms but in those more progressive and hospitalized children, starting late could be effective as well.

The conditions at risk that increase the risk of complications have already been mentioned so I am not going to go into this and these would be again in line with the CDC and this is a table that is included in the AAP recommendations to start treatment of influenza in children.

The antivirals, we continue to rely on the neuraminidase inhibitors so oseltamivir, zanamivir, and peramivir which can all be given to children. This table is also available in the AAP recommendations and you can see that for oseltamivir, you can start as early as birth if necessary so young children can receive treatment very early on and zanamivir because of the inhalation requirements by mouth, it’s for older children 7 and older while peramivir which is a single dose can be given intravenously starting at 2 years of age. The recommendations for prophylaxis are a little bit different and again, for prophylaxis, we want to think about those children who cannot be vaccinated or whose immune system does not allow them to respond well to vaccines or who might be at particular risk and not be protected from vaccine when influenza is already circulating.

My conclusion are that as you can see, the American Academy of Pediatrics recommends that influenza vaccine is given to everyone starting at 6 months of age and that we recommend two doses the first time or for those who are incompletely immunized and are 6-8 years of age. Everyone else should receive one dose, so 9-17 years of age and those who have been previously vaccinated and especially focusing on the groups at risk but again, everyone could be considered at risk not necessarily because they have an underlying medical condition but because of age. Complete vaccination by the end of October and continue to vaccinate throughout the season. You can use trivalent and quadrivalent without preference. The most important point here is to make sure that children are vaccinated and that you don’t wait for a vaccine to be available and as we mentioned before, this year’s primary choice is IIV with LAIV an option for those who are 2 or who would not otherwise be vaccinated. We have no special precautions for egg allergy and the only real contraindication that is cited is allergic reactions to any component of the vaccine. Therefore, you know, probably one last comment is that we will continue to monitor, of course, along with the data that CDC provides any activity of influenza this season and as well which type of influenza virus is going to be the predominant one and how the vaccines are going to be performing this year. With that, I thank you for your attention. I am sorry, I have this one last slide.

Neuraminidase inhibitors, the recommendations are the same so I don’t have any additional points after that. Thank you so much.


Ibad Khan:

Thank you so much, Dr. Grohskopf and Dr. Munoz. We will now go into our Q and A session. Please remember, you may submit questions through the webinar system by clicking the Q and A button at the bottom of your screen and then typing your question. We already have quite a few questions so I am going to go ahead and get started with our questions.

Our first question states you mentioned that high morbidity and mortality in children, especially when they are co-infected with MRSA, is this a nosocomial infection or are there other complications related to this relationship between these co-infections?


Flor Munoz:

So thank you for that question. Actually, it’s not necessarily a nosocomial infection. Children that have either MRSA or pneumococcal secondary bacterial infections tend to actually come from the community and we saw that during the pandemic. Unfortunately, this is a well-known complication of influenza, particularly with those two bacteria which are bacteria that are carried in the respiratory tract and, therefore, carriers can become infected when they have influenza in addition to just being carriers so it’s not necessarily a nosocomial complication.


Ibad Khan:

Thank you for that. Related similar to that topic is another question we received. So should asymptomatic close contacts such as family members be treated with prophylaxis antivirals such as Tamiflu?


Flor Munoz:

So I can start with that and maybe Dr. Grohskopf has other comments so the indications for chemoprophylaxis are related to the risk for the individual who is in contact with an index case so it’s not automatic that every household contact should be put on prophylaxis. I think it’s important to keep in mind the host status and the vaccination status of those individuals and then follow the recommendations for chemoprophylaxis based on that.


Lisa Grohskopf:

Just to follow on that. I would agree. Basically, you have to consider the health status of the individual who has been exposed and certainly, if they meet those criteria of severe illness or being hospitalized or being in a high-risk group, you would certainly be recommended to do that but there may be some others for whom it would be more of a consider rather than a recommend.


Ibad Khan:

Thank you both. Our next question asks what would you recommend as the best way to protect children under 6 months old from influenza?


Flor Munoz:

I can start also with that one and, indeed, they are group of concern but keep in mind that we have a beautiful system in place which is the transfer of maternal antibodies from mother to infant and it is very clear now through clinical studies and also epidemiologic studies that infants born to mothers who receive their influenza vaccine during pregnancy are protected against influenza, protected against hospitalization from influenza and even from complications of influenza in the first few months of life. It is very, very important I think to make sure that mothers who are pregnant or will be delivering during the influenza season are vaccinated against influenza for themselves but also because it is one way of protecting their babies. The other way to do this is to make sure that household contacts – so in this case, this cocooning strategy so to speak where the baby is not able to be vaccinated but can be indirectly protected if no one in the household gets the flu so making sure that siblings, parents, grandparents, caretakers are also vaccinated is another method of prevention.


Ibad Khan:

Thank you, Dr. Munoz. Speaking of immune response, we have a question that asks that if patients are vaccinated in early September and immune response may wane in a couple of months, what is a strategy to protect them as the influenza season peaks?


Flor Munoz:

Let me actually clarify that and I also will ask Dr. Grohskopf to comment on this because it doesn’t mean that their immunity wanes at 2 months. So the clarification I would like to make is that for any vaccination – this is not just exclusive for influenza – any vaccination after you receive a vaccine, your immune system is going to actually take a week or two to start developing or producing the antibodies and in general, you do see a peak response a month to two months after the vaccination. That’s the peak so a natural decay of antibody after that peak is expected for any vaccine and so it doesn’t mean that you completely lose the antibodies after two months. It is actually possible to see antibody levels and measure them for several months after that and even years after that. The point here is that waning immunity is not necessarily a concern in terms of increasing the risk of children to get influenza, mainly because for the most part, you will see that there is also memory immunity so if the child gets exposed, those antibody levels would actually increase and have some memory response that will allow them to protect and indeed, there is a need for a certain level of antibody to be more likely to be protective but that natural decay that occurs after vaccination is not sufficient to really compromise the effectiveness of the vaccine as best as we know right now in terms of breakthrough disease and I think that at this point, more studies are being done. Like I said, most of the data is coming from adult studies. Dr. Grohskopf, would you like to comment on that?


Lisa Grohskopf:

Yeah, thanks. I agree. I think the only thing I would add is that the data on waning immunity is not consistent across seasons or populations or across studies necessarily. We see studies, for example, of antibody levels – in not all of those studies did the antibodies actually decline. There are some studies that are actually VE studies. Typically, these are observational case control-type studies that have shown vaccine effectiveness to drop over the course of the season but not consistently in every study. It may be more of an issue with older adults, for example, than it is for younger adults and children and it also may be something that is more of a problem with H3 viruses than with the H1 viruses but overall, the literature is really a bit too inconsistent to really know. There is a lot that I think we have yet to learn about this.


Ibad Khan:

Thank you both for answering that question. Noting that this call is related to pediatric patient population; however, this is a question that popped up a couple of times in our Q and A so we have to ask. Can you describe and kind of elaborate on the increased risk to Native American populations, assuming that it also would be prevalent to Native American pediatric population. What are some strategies that you would like to recommend or reiterate for protecting that particular patient population?


Lisa Grohskopf:

Do you want me to take that, Dr. Munoz?


Flor Munoz:

Please do, yes.


Lisa Grohskopf:

So the increased risk for not just American Indian/Alaska native populations in the US but also in indigenous populations in other parts of the globe to my knowledge was really first noted and kind of elucidated during the beginning of the 2009 pandemic and there have been a couple of studies that have looked at that population group to try to tease things out and determine if it’s something inherent to the population or if there are some other factors that influence it but the bottom line is that during that period – and since we also still have that virus circulating – that group was added to the list of high-risk individuals so really I think probably the most important thing to suggest in terms of prevention is that the most important thing is to get vaccinated as with any other group and should you get infected and should you get flu or have symptoms of flu, see a physician. We have the list of three basic preventive strategies. Everyday health activities – try to avoid sick people, try not to go out and spread your illness if you are sick, get vaccinated, and take antivirals if your healthcare provider prescribes them.


Ibad Khan:

Thank you, Dr. Grohskopf. Next question is related to the newer and upcoming antiviral in the pipeline, Baloxavir, and the question is if Baloxavir is approved and available, would you recommend that it be used in an off-label way similar to other antivirals or do we not have that information yet?


Lisa Grohskopf:

I don’t think we have enough information to be able to answer that yet.


Ibad Khan:

Thank you. Our next question is what are the biggest takeaways that you would like clinicians to know about the difference between last flu season and this season?


Lisa Grohskopf:

I would say we did have a bad season last year. We can’t predict what this season is going to be like yet. The most important thing is get vaccinated.


Ibad Khan:

Thank you. What led to AAP’s recommendation for the limited use of LAIV4 for the 2018-2019 influenza season? I know you discussed it during your presentation but I know that is one of the points that was different last season so if you would like to please share that with us.


Flor Munoz:

Sure and again, I would refer you to the AAP news publication and also to the MMWR to look at the specific data but as mentioned, the main concern was not having effectiveness data for the formulation that is being used for this year; however, there is no concern in the sense that it wouldn’t be effective at all so that’s why there is an option to utilize it. I think that the main piece of information that we would like to see is effectiveness data with this vaccine. So we should be able to have that information. There is reassurance that this vaccine should be effective as well and like I said, it’s not a vaccine that should not be used at all. As long as children can get vaccinated, that is important and we should have information to update the recommendations in the next year.


Ibad Khan:

Thank you, Dr. Munoz. At this time, we would like to conclude our Q and A session. On behalf of COCA, I would like to thank everyone for joining us today with a special thank you to our presenters, Dr. Grohskopf and Dr. Munoz.

The recording of this call and the transcript will be posted within the next few days to the COCA website at emergency.cdc.gov/coca. Again, the web address is emergency.cdc.gov/coca. All continuing education for COCA Calls are issued online through TCEOnline, the CDC Training and Continuing Education Online system at www.cdc.gov/TCEOnline.

Those who participated in today’s COCA Call and would like to receive continuing education should complete the online evaluation by October 29, 2018 and use course code WC2922. Those who will participate in the on demand activity and wish to receive continuing education should complete the online evaluation between October 29, 2018 and October 30, 2020 and use course code WD2922.

Please join us for our next COCA Call, where the discussion will be on the Multi-State Hepatitis A Outbreak. The date is yet to be determined.

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Page last reviewed: November 19, 2018