2025 – 2026 Clinical Recommendations for Seasonal Influenza Prevention and Control

Good afternoon. I'm Captain Ibad Khan and I'm representing the clinician outreach and communication activity KOKA with the Office of Emergency Risk Communication at the Centers for Disease Control and Prevention. I'd like to welcome you to today's COCA call 2025 to 2026 clinical recommendations for seasonal influenza prevention and control. All participants joining us today are in listenonly mode. To view live captions, choose more from your menu bar. Choose language and speech, then choose show live captions. If you would prefer to view only the content on the slides without the distraction of seeing the thumbnail view of the gallery of attendees, you can switch your settings to focus mode. To enable focus mode, once again, go to your menu bar, click view, then choose focus on content. Free continuing education is offered for this webinar and instructions on how to earn continuing education will be provided at the end of the call. In compliance with continuing education requirements, all planners, presenters, and moderators must disclose all financial relationships in any amount with ineligible companies over the previous 24 months, as well as any use of unlabeled product or products under investigational use. CDC are planners, presenters and moderator wish to disclose they have no financial relationships with ineligible companies whose primary business is producing, marketing, selling, reselling or distributing healthcare products used by or on patients. content will not include any discussion of the unlabeled use of a product or a product under investigational use with the exception of Dr. Dr. Lisa Groskoff's discussion of the CDC ACIP influenza vaccination recommendations that include discussion of the unlabeled use of influenza vaccines in the recommendations for persons with a history of egg allergy and for solid organ transplant recipients ages 18 through 64 years. With regard to persons with a history of egg allergy, history of severe allergic reaction, for example, anaphilaxis to the vaccine or any of its components which include egg for certain vaccines is a labeled contraindication to receipt of most trivalent inactivated influenza vaccines and trivalent live attenuated influenza vaccine. However, ACIP recommends that all persons ages 6 months or olders with egg allergy receive influenza vaccine. Any influenza vaccine, egg based or non- eggbased, that is otherwise appropriate for the recipients age and health status can be used. With regard to solid organ transplant recipients ages 18 through 64 years, the trivalent highdosese inactivated influenza vaccine and the trivalent aduanted inactivated influenza vaccine are approved for persons ages 65 years or older. However, ACIP recommends that solid organ transplant recipients ages 18 through 64 years who are receiving immunosuppressive medication regimens may receive either the trivalent highdosese inactivated influenza vaccine or the trivalent aduanted inactivated influenza vaccine as acceptable options without preference over other age appropriate trivalent inactivated influenza vaccine. or trivalent recombinant influenza vaccine. In addition, content will not include any discussion of the unlabeled use of a product or a product under investigational use with the exception of Dr. Tim Uki's discussion that CDC recommends Osel Tamavir treatment for persons of all ages. FDA approval is for persons ages 14 days and older and that CDC recommends Osalovia treatment for hospitalized patients. FDA approval is for outpatients. CDC complies with applicable federal civil rights laws and does not discriminate based on race, color, national origin, age, disability, religion, or sex. To learn more, visit www.hh hhs.gov/civil rightights. At the conclusion of today's session, participants will be able to accomplish the following. Highlight key recommendations in the CDC Advisory Committee on Immunization Practices document prevention and control of seasonal influenza vaccines. Recommendations of the Advisory Committee on Immunization Practices, United States 2025 to 2026 influenza season. Describe influenza testing recommendations in outpatients and in hospitalized patients with suspected influenza and review antiviral medications for influenza and CDC's recommendations for antiviral treatment for patients with suspected or lab confirmed influenza. After the presentation, there will be a Q&A session. You may submit questions at any time during today's presentation via the MS Teams platform. Please note that the ability to ask a question during the live webinar is limited to the first thousand attendees who joined the webinar. If you are unable to ask a question during the webinar, you may submit your question after the live session by emailing [email protected]. Kindly note that we receive many more questions than we can answer during our webinars. If you're a patient, please refer your questions to your health care provider. And if you're a member of the media, please contact CDC media relations at 4046393286 or send an email to media at cdc.gov. I would now like to welcome our presenters for today's CocaCol. We are very pleased to have with us Dr. Dr. Tim Uki, who's the chief medical officer in the influenza division at the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, and Dr. Lisa Groskoff, who's a medical officer in the influenza division at the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention. It is my pleasure now to turn it over to Dr. Ueki. Dr. Uki, please proceed. >> Thank you, Captain Khan. Today's presentation is an update on influenza United States 2025 2026 influenza season. Next slide. So the findings and conclusions in this presentation are those of the speakers and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Next slide. In this presentation, we'll describe 2024 2025 seasonal influenza epidemiology and disease burden. We'll discuss 2024 2025 influenza vaccine effectiveness and influenza vaccine recommendations for the current 2025 2026 season and we'll discuss influenza testing and antiviral treatment recommendations. Next slide. We'll just start off with key points of this presentation. Last season the 2024 2025 influenza season was a high severity um influenza epidemic in the US. There was high morbidity and mortality and a wide range of respiratory as well as non-respiratory complications. Influenza vaccine effectiveness last season was moderate against both uncomplicated illness and severe disease in the US. Now we know that um from our surveillance influenza activity is increasing in the US right now and therefore that the time to get vaccinated for this season is right now for those persons aged 6 months and older who have not received influenza vaccine this season. Molecular influenza tests are recommended. That includes rapid molecular tests for outpatients as well as rapid and other molecular tests for hospitalized patients as well as the use of multipplex assays when indicated. Influenza antiviral treatment is recommended as soon as possible for outpatients at increased risk for influenza complications. Ideally, antiviral treatment should be initiated within two days of illness onset with either oscult. However, for progressive or severe disease, regardless of the time since illness onset, including greater than 2 days after illness onset, osel tamavir treatment is recommended. For hospitalized patients, osculted as soon as possible. Uh, next slide, please. So, we'll just start off with some background information about influenza as well as influenza activity and disease burden. Next slide. So background on seasonal influenza. This is a contagious respiratory illness caused by infection of the respiratory tract particularly the upper respiratory tract with influenza A or B viruses. And these this is associated with seasonal influenza epidemics during fall, winter and spring in temperate climates of the northern and southern hemisphere uh including in the US and worldwide. Transmission is via large and small infectious respiratory particles that are expelled from an infected person to a susceptible individual in close proximity. The incubation period from the time of exposure and infection to uh onset of symptoms is approximately 1 to 3 days. So this is a short incubation period. The spectrum of infection ranges from asymptomatic infection and most people experience mild uncomplicated illness but there are some people that do progress to severe complications including resulting in death. Signs and symptoms typically of uncomplicated influenza include an abrupt onset of signs and symptoms. This is not typically gradual onset of symptoms over a number of days but typically abrupt onset and this may be fever or feeling feverish or chills but not all patients with uncomplicated influenza actually manifest fever or feverishness. Um non-productive cough is common, sore throat, runny or stuffy nose, headache, muscle or bodyaches and fatigue. Most people do experience uncomplicated influenza. Next slide. However, there are people that do experience complications of influenza and these include moderate or severe to um to critical complications. Examples of moderate complications include otitis media in young children or sinus infections as well as exacerbation of underlying chronic disease that is not severe. However, there are many people that have underlying chronic disease that may not be well controlled or influenza may precipitate a very bad exacerbation of that underlying condition and that may um require uh hospitalization. There are many different respiratory complications of influenza and most commonly that is pneumonia. Cardiac complications uh can occur um but they are more common in people particularly adults with underlying coronary artery disease but uh in young children and in some adults there are rare complications that can occur in otherwise healthy persons. neurologic complications. There is a wide spectrum of neurologic complications that can be transient to very fulminate. Um and bacterial co- infection community acquired is not uncommon um to result in severe disease. And the most uh common bacterial uh that are associated with bacterial co-infection with influenza requiring hospitalization are staflaccus orius both methasylan sensitive and methasylan resistant streptocous pneumonia and group a streptoccus. There are muscularkeeletal complications, inflammation of muscle tissue that can be mild but in severe cases can result in muscle breakdown and rabdtomyolyis. Multi-organ failure um occurs in patients with critical illness particularly respiratory and renal failure as well as septic shock. And don't forget healthc care associated infections um in people particularly who um are intubated because both uh bacterial or fungal ventilator associated pneumonia can occur. Next slide please. So influenza associated and seephalopathy common and most well described in children. This is a known complication of influenza. We we do not have established US surveillance um for this complication and basically it's me influenza virus infection of the respiratory tract can precipitate uh neurologic complications that u manifest in impaired consciousness or altered mental status with brain dysfunction. This may be very transient over a number of hours and self-limited but it also can be fulminant with progression to coma and death within 24 hours. Um the most severe syndrome within influenza associated in sephylopathy is called acute necroizing and seephalopathy or A&E. And what you see in the image is um the the two arrows point to bilateral theamic um inflammation which is the hallmark of acute necrotising and seephalopathy. Last season we started to hear about some of these cases in January and February and we requested um that clinicians and health departments report possible cases of an influence associated and sephylopathy to CDC. We had 109 influenza associated encphylopathy cases. 37 that had acute necrotising and sephylopathy. These were typically young children with a median age of 5 years. Of note, 55% were otherwise healthy without underlying medical conditions. And of uh particular importance was that the vast majority of these cases were not vaccinated. only 16% of vaccine eligible had received influenza vaccine last season prior to um their illness. The median time from symptom onset of influenza to neurologic symptom onset was 2 days. So rather fulminate um after uh influenza signs and symptoms had occurred. There was very high severity. 74% were admitted to a pediatric intensive care unit. 54% required invasive mechanical ventilation and 19% died and of those with acute necrotising and sephylopathy AMA 41% died. Next slide. So we know from many kinds of studies there are certain groups that are increased risk for influenza complications and severe illness. And these include young children aged less than two years and adults 65 years and older. Persons with chronic medical conditions including pulmonary or cardiovascular excluding isolated hypertension and persons with underlying renal hypatic neurologic conditions including those who have had a stroke and neurodedevelopmental, hematic, metabolic or endocrine disorders and those with certain disabilities. Persons who are imuno compromised, persons with extreme obesity, children and adolesccents who are receiving aspirin or salicellate containing medications chronically who might be at risk for ry syndrome after influenza virus infection. Residents of nursing homes and other long-term care facilities. Pregnant women and those up to two weeks postpartum. people from certain racial and ethnic minority groups including non-Hispanic black, Hispanic or Latino and American Indian or Alaskan native persons. Next slide. So last season was a predominantly influenza A season. There was a low amount of influenza B circulation mostly occurring a little bit later in the season and we had an almost even proportion of influenza AH1N1 PDM9 viruses circulating as compared to influenza A H3N2 viruses circulating and the season overall peaked in late January early February on a national basis with some differences regionally as expected. Next slide. So over a number of seasons and here are 10 season data from um a number of seasons and there is a wide range of severity from season to season. We know that some influenza epidemics are milder than others. Last season was more severe. Um but typically there's an estimated range of 9.3 million to 41 million illnesses due to influenza. um resulting in approximately 120,000 to 710,000 hospitalizations and a range estimated from 6,300 to 52,000 deaths uh per per season. So the bottom line is that there is a variability in the severity of influenza epidemics in the US. Next slide. Now this is data um uh from 10 seasons and what you see in the red dotted line is last season and this is cumulative lab confirmed hospitalization rates. So this is populationbased uh surveillance and you can see that last season had very high hospitalization rates. This is all ages compared to prior seasons. Next slide. What this shows is a breakdown by age group. Same kind of data to highlight the fact that typically in an influenza season, the highest hospitalization rates, cumulative rates are in those 65 years and older, followed by those 50 to 64 and then followed by young children. And of note, you can see that uh adults 18 to 49 years and school age children typically have much lower um rates of hospitalization due to lab confirmed influenza than other age groups. Next slide please. When you look at children, same kind of data. Cumulative influenza associated hospitals hospitalization rates are highest the younger the age. So you can see the highest are those less than one and then school age kids and particularly adolesccents have much lower hospitalization rates. Next slide. Uh what this slide illustrates looking at different age groups is that in older adults aed 65 years and older, you can see in the purple the deaths and the green the hospitalizations that older adults uh dominate hospitalizations and deaths due to influenza in the United States. Next slide. Um since the 2004 2003 influenza season, pediatric influenza associated death has been nationally reportable. So we've been tracking this for many years. What you see are four seasons including last season. Um and unfortunately these are uh the majority of these are preventable. Uh and this is really really tragic. Um last season uh the latest data I've incorporated uh data that will be presented um in the weekly flu view. Tomorrow we had one more death reported. So 288 deaths reported for last season. This is um the highest number of deaths for a seasonal influenza epidemic since we've been keeping track and clearly highlights the fact that we need to do a much better job at preventing influenza and preventing influenza associated death in children in the United States. Next slide. So last season preliminary estimates uh of uh last season's disease burden are that there were a range of 47 to 82 million influenza illnesses resulting in 21 to 37 million estimated medical visits and an estimated 610,000 to 1.3 million hospitalizations and a wide estimate of 27,000 to 130,000 influenza associated deaths in the US. There will be uh in the uh a little bit uh in the near future there'll be some final estimates of influenza disease burden for last season. Next slide. That's all to say that last season by all indicators was a high severity season and one of the highest that we have experienced in the US. Next slide. Um, in August of this year, CDC influenza division laboratory scientists identified a new influenza AH3 and2 virus subclaid K, which is antigenically drifted uh, compared with the influenza AH3 and2 vaccine virus for the 2025 2026 uh, influenza vaccine. Now um this has drawn a lot of attention with early season activity reported in a number of countries associated with this uh influenza A H3 and2 virus subclaid K. Um and uh we have not been experiencing such early influenza activity in the US as some other countries, but um influenza activity is now increasing throughout the US and influenza A H3 and two viruses to date are the most frequently reported uh influenza viruses. Although this is very early and we cannot predict um whether these viruses will predominate throughout the season but among those H3N2 viruses that we have characterized so far at CDC this season 87% belong to the subclaid K. Um and none of the three influenza AH3 and 2 viruses collected this season in the United States were well recognized by post infection ferret anti-era against the northern hemisphere 2025 2026 influenza vaccine strains. Next slide. It will be updated tomorrow as usual on a weekly basis every Friday. Um just to show that uh public health laboratories have reported that the vast majority of influenza viruses identified in the US this season uh have been influenza A viruses and of those more than um 75% have been this influenza AH3 and2 virus and of those H3 and two viruses uh the vast majority have been this subclate K. Um so there is still some influenza AH1 PM9 viruses that have been uh identified almost a quarter but um uh it's it's hard to say um what will happen throughout this season and that's why we need surveillance to really track this with a low proportion of influenza B viruses identified to date. Next slide. So with that I'm going to turn over to Dr. Gkoff. Hey, thanks very much Dr. Yaki. Um, I'm going to be taking you through a brief overview first of what is new in the 2025 2026 influenza vaccine recommendations. Next slide, please. Now, in the interest of time, we're going to focus on mostly what's new, but I'm going to mention some of the old stuff, too. Um just to to remind folks um to summarize some of the topline items that are the same as last season as previously routine annual influenza vaccination is recommended for all persons aged 6 months and up without a contraindication to vaccination. So anybody in that age group 6 months and older who does not have a contraindication to receive flu vaccine is recommended to be vaccinated and this is to protect against influenza and its complications. Also, as previously, multiple formulations and brands of the trivalent influenza vaccine are available in the US for the 202526 influenza season, including inactivated influenza vaccines or IIV3s, which are available in multiple brands, the recombinant influenza vaccine or RIV3, um, also known as flu block. It's the name of that one. Um, and the live attenuated influenza vaccine or LIV3, which is flu mist. Um, also similar this season, just a couple of things to mention. Um, there are, uh, like we said, a number of vaccines available, a total of nine unique brands this season, as there were last season. All are trivalent. Um, each has its own approved age range for approved use by FDA. In general, people should get a vaccine that is appropriate for their age. That is, that's been approved for their age. Um, the one exception is, as uh, Dr. Dr. Con mentioned at the top solid organ transplant recipients who are between the ages of 18 and 64 years and are on imunosuppressive medication recommend uh medications can receive as acceptable options either the highdose inactivated or the advent that's not a preferential recommendation that's basically considered an acceptable option they can also receive any other vaccine approved for their age. Um second point, we don't have any preferential recommendations for a particular vaccine for any one person. For most people, there's going to be more than one acceptable option. Um but the one pref one exception is the preferential recommendation for adults 65 and older for whom the highdosese vaccine, the recominant vaccine or the adgivvented vaccine are preferentially recommended. If none of those are available, any other um age appropriate vaccine is acceptable. And lastly also as mentioned at the top um for egg allergy we still get a lot of questions about egg allergy. Egg allergy is no longer a consideration for the selection of influenza vaccines. Any person with egg allergy of any severity can get any vaccine for influenza that's otherwise appropriate for their age and health status. So I'll go to the next slide now. So now we're going to focus on what's new and the recommendations for this year. Um the 202526 influenza vaccination recommendations were published in MMWR on August 28th of this year. It's a shorter format this year that focuses primarily on updates for the season, but you will see um some highlights of some things that were from the previous season including the three things I just mentioned. Um the new information just to summarize it quickly for 25 2020 uh 202526 is that um we have the updated US influenza vaccine composition. As you know, composition of flu vaccines is reviewed every year because influenza viruses are constantly changing. You can find more information about the exact composition in the influenza statement in the MMWR. But um just to mention briefly, um there's an update in the H3N2 virus for this season. Second, we have the availability of flu mist, the intraasal live attenuated influenza vaccine or LIIV3 as we abbreviate it for self or caregiver administration. We're going to go over that in another slide very shortly. Um, next, a new approved age range for flu block, which used to be recommended for 18 and up, but now is recom I'm sorry, approved for 18 and up, but now is approved for 19 uh 9 years and up. We'll talk about that in another slide shortly. And lastly, there's a new recommendation that only vaccines that do not contain thyosol as a preservative are recommended for all recipients. So seasonal influenza vaccines um historically the multid-dosese vile formulations have contained thyarosol as a preservative to um to prevent bacterial or other microbial growth. Um there's a recommendation for this season that only seasonal influenza vaccines that do not contain thyarosol as a preservative are recommended for all recipients. Next slide. So this slide and the one that follows just have a little bit of updates on the two vaccines that had um changes in their uh FDA licensing. Um the first we're going to talk about is Flumist LIIB3 which is now approved for self or caregiver administration. Essentially consumers can now order Flumist for delivery for eligible recipients. Eligibility screening is performed by an online pharmacy um based on the ACIP criteria uh that currently exists for who is recommended to get fluist or who is not recommended to get fluist because LIV is not recommended for some populations. LIV is approved for self- administration for persons aged 18 through 49 years or if the recipient is younger. administration by an adult caregiver aged 18 or older if it's being given to a recipient aged 2 through 17 years. The ACIP recommending recommendations regarding the appropriate populations, contraindications or precautions to the use of LIIB are the same for self or caregiver administration as they are for healthcare provider administration. So, of note, one thing to remember, LIIV is approved and recommended only for ages 2 through 49 years. So it has a bit of a narrower age band than some of other vaccines do and it's not recommended in pregnancy imuno compromise and in certain other medical conditions which are detailed in the 202526 influenza recommendations. Next slide. We next have a new approved minimum age for flu block or RIV3. Um this is the recombinant influenza vaccine. It was previously approved by FDA for those 18 years and older. The new approved age indication is 9 years and older. This approval was based on a study which compared immune response and safety of flu block among 9 through 17 year olds with that among 18 through 49 year olds. Next slide. So for our next topic, we're going to go over briefly um influenza vaccine effectiveness estimates focusing primarily on work from our four CDC influenza vaccine effectiveness networks. Next slide. CDC assesses influenza vaccine effectiveness annually through four networks which provide estimates in the reduction in medically attended influenza illness associated with influenza vaccination. And these networks include the new vaccine surveillance network or NVSN which examines influenza associated medical encounters in inpatient and outpatient settings among children. The virtual SARS kov influenza and other respiratory viruses network or vision which examines influenza associated medical encounters in inpatient outpatient settings among children and adults. the US flu vaccine effectiveness or US fluve network which as examines influenza associated medical encounters in outpatient settings among children and adults and the investigating respiratory viruses in the acutely ill or IV network which examines influenza associated medical encounters in inpatient settings among adults. Um so you see there's a bit of a variance in among these four networks in the age groups they cover and whether they cover inpatient, outpatient or both. But taken together, these networks cover inpatient and outpatient influenza illness in both children and adults. Next slide. Now, some of these networks, you may have noticed by their names, they um cover not just flu viruses, but other respiratory viruses, but the results I'm going to present to you are focusing on flu only. And these are preliminary estimates for the season that just ended 202425. So first up we have preliminary influenza vaccine effectiveness estimates from the four four networks for the pediatric population that is children aged 6 months through 17 years. Estimated vaccine effectiveness ranged from 32% to 60% for outpatient illness and 63 to 78% for inpatient influenza illness. All of these estimates are statistically significant. That means the 95 confidence interval does not cross zero. Um, and also this is for all viruses, all subtypes. As would be expected, there's some variability in the ve estimates among the networks which might reflect regional variations in circulating viruses. The ve estimate is slightly lower here for US fluve network compared with the other networks. This network had a higher proportion of subtyped specimens that were H3N2 viruses at 67% compared for example with the NVSN for which the proportion that were H3N2 was 48%. Vaccine effectiveness overall is generally lower for H3N2 viruses than it is for H1N1 viruses. Next slide. These are the preliminary 2425 influenza vaccine effectiveness estimates from the same four networks for adults aged 18 years and older. Estimated vaccine effectiveness range from 36 to 54% for outpatient influenza illness and 41 to 55% for inpatient influenza illnesses. These estimates are also statistically significant. Again, we see a slightly lower VE estimate from US fluve network, which again might reflect regional variations in circulating viruses, particularly the proportion that were HVN2 in circulation. Taken together, these interim estimates of 2425E indicate that influenza vaccination was effective in preventing medically attended influenza associated illness in children, adolescence, and adults in the United States. Next slide. So, we've talked a little bit about the past 24-25 season. Um, having discussed that, we're going to pivot a little bit and briefly consider the season in front of us, 202526. Um, at this time, we don't really know what VE is going to be like for this season. Activities really getting underway in the US and it takes a little while before accumulating enough activity and specimens to be able to calculate VE. As Dr. Uki mentioned um we had the new drifted H3N2 subclaid called subclaid K which has been identified and which is antigenically different compared with the 2526 influenza AH32 virus that is the virus that's represented in the current season vaccine. It's too early to know what impact exactly this new subclave will have on the influenza vaccine effectiveness for this season. However, early estimates of 2526 influenza VE against influenza AH3N2 virus associated hospitalizations in England where the flu activity is described as having begun earlier than usual um for the season and which is also se seeing a predominance of subclaid K. Um, ve estimates preliminary so far have remained within the expected range of 70 to 75% for children and 30 to 40% for adults, suggesting at this point that influenza vaccination remains an effective tool in preventing influenza related hospitalizations for the season. So far, influenza vaccine effectiveness networks continue to collect real world data to produce early estimates of influenza v in the United States. Next slide. And with that, I'm going to turn things over back uh back over to Dr. Yucky. Thank you for listening. >> Uh thanks Dr. Grosskoff. Now I'll I'll cover influenza testing. Next slide, please. So why use influenza tests? And the main reason is because a clinical diagnosis of influenza may be inaccurate because influenza can present with non-specific signs and symptoms that overlap with other respiratory virus infections. And this is true both for uncomplicated illnesses as well as for severe illness. Um now we know from uh various epidemiologic studies that clinical predictors of influenza typically are abrupt onset of fever with cough, cough, fever, runny nose or muscle aches and then fever particularly um higher temperatures and cough. But use of influenza tests can really help guide clinical management decisions and this includes whether to start antiviral treatment. There are studies to suggest that uh identifying influenza may actually reduce prescriptions for uh unnecessary antibiotics uh may reduce the use of other diagnostic tests and actually will help inform infection prevention and control measures. Next slide. So the point of this slide is that influenza viral shedding typically peaks within 24 hours of illness onset. You can detect influenza viruses in the upper respiratory tract of infected individuals one day before illness onset. U and these virus levels peak within 24 hours after symptom onset. We know that the highest infectious period for most people uh who are who are imunompetent is within three days after illness onset. And what you see from the figure on the right is that uh influence of viral RNA detection in the upper respiratory tract really drops off after 2 to three days after symptom onset. So um there are some exceptions and that is very young children can be infectious for longer periods and critically ill patients might have longer influenza viral replication in the lower respiratory tract. Next slide. So what are the best respiratory specimens for detecting seasonal influenza viruses? So the best respiratory specimens are high up in the uh respiratory tract and that would be nasopereneal swabs ideally collected within 3 to 4 days of illness onset. And these viruses can be generally detectable for about 3 to 4 days by antigen detection tests but longer about 5 to 6 days by molecular assays in people with uncomplicated disease. um but for longer periods in infants and imuninompromised persons. Uh depending upon the test other acceptable specimens may be nasal swabs particularly mid-turbinate nasal swabs, nasoparangal aspirates, nasal aspirates or combined nasal and throat swabs. In general for detection of seasonal influenza A or B viruses, uh throat swabs will have the lowest yield. So you really want to go higher highest up in the uh uh res upper respiratory tract. Um and just to say that in imunosuppressed persons there can be longer um viral replication and longer duration of u virus detection. Now we know that in persons who have um severe disease particularly critical disease with uh say influence of viral pneumonia there can be prolonged viral replication. Um and in fact uh some patients may be able to clear uh influenza viruses in the upper respiratory tract but still have ongoing replication in the lower respiratory tract. And we have some data from the 2009 H1N1 pandemic when the diagnosis of influenza in some critically ill patients um these are adult patients was made by actually um uh using bronchi alvolola lavage fluid specimens for testing. uh when upper respiratory tract specimens tested negative for influenza. Next slide. So there's a wide range of influenza diagnostic tests available to detect influenza viruses and respiratory specimens. These differ by the time to produce results, what information is actually available, what are approved respiratory specimens and what is the approved clinical settings. And they also vary by accuracy. So in general there are the antigen detection tests and some of these are multipplex assays and some are also available for over-the-counter use uh at home. Um there are the others are nucleic acid detection we refer to as molecular assays. Um there are both singleplex as well as multipplex assays uh that detect other respiratory viruses particularly SARS KV2 and there's one molecular test um that can be used over the counter at home. Um some of these tests are uh clea waved uh for point of care that can be done uh at the bedside um or in any clinic and others uh the majority are moderately complex which require testing in a clinical laboratory and then there are highly complex tests that require testing to be done in large clinical laboratories or public health laboratories. Next slide please. So a summary of these kinds of tests are the rapid antigen detection tests that can produce a result in 10 minutes. Um you get only an influenza A or type A or type B result. Um no influenza A subtype information. Uh the advantage is a quick uh result. The disadvantage is low to moderate sensitivity compared to molecular assays. There are some multipplex antigen assays as I mentioned that are antigen detection tests that can detect SARS KV2 as well as other respiratory viruses. Now the molecular assays as I mentioned are um have much higher accuracy. They have much they have moderate to high sensitivity and both uh antigen tests and molecular tests have high specificity suggesting that false positive results are low with either kind of test. However, with the rapid diagnostic tests, false negative results are more likely particularly during peak community influenza activity. Um there are some molecular assays that don't produce results so timely. The rapid assays do produce results in 15 to 30 minutes but others may take an hour or several hours to do. Uh the most important issue is to properly interpret the test results especially when interpreting negative results and thinking about and actually might have influenza and interpreting the results properly particularly those of antigen detection tests. Slide. So recommended influenza tests for outpatients are rapid influenza molecular assays. These are recommended over rapid influenza antigen tests and again it's because of the higher sensitivities of the rapid molecular assays. Um the for hospitalized patients molecular assays are recommended including RTPCR and rapid antigen detection tests in uh immunofllororesence assays which are also antigen detection tests. These are not recommended and should not be used unless molecular assays are not available uh at a hospital. For imunompromised patients, one should also consider other respiratory viruses and so multipplex assays that target a wide panel of respiratory pathogens including influenza A and B viruses are recommended. Some key points for clinicians. Do not order viral culture for initial or primary diagnosis of influenza because the results will not be timely to inform clinical management of the patient. And do not order corology for influenza because this re requires uh collection of paired acute and convolescent serum specimens collected two to three weeks apart and that corological testing needs to be done at specialized laboratories. Next slide. So self-nowledge check which influenza tests for respiratory specimens are recommended to inform clinical management of hospitalized patients with suspected influenza. Select all that apply. A rapid influenza molecular assays. B rapid shell vial culture. C RTPCR influenza assays. D multipplex rapid antigen assays. E multipplex immunofllororesence viral respiratory panel assays. or F uh multipplex molecular assays. Uh next slide. So the answer is A rapid influenza molecular assays, C RTPCR influenza assays and F multipplex molecular assays. And the rationale is that molecular influenza assays are recommended due to high sensitivities to detect influenza viruses in respiratory specimens. However, antigen tests including multipplex immunofllororesence and multipplex antigen tests and viral culture are not recommended for hospitalized patients with suspected influenza. Next slide. Let me move on to summarize influenza antiviral treatment. Next slide. So recommended antivirals for treatment of influenza this season. There are four FDA approved antivirals that are recommended and there is no evidence of resistance among circulating seasonal influenza A or B viruses to these um recommended antivirals and all of these have demonstrated efficacy in randomized control trials uh versus placebo and they are FDA approved for early treatment within two days of illness onset in outpatients with uncomplicated influenza. A and these include two classes the neuromminidase inhibitors and the cap dependent endonucleus inhibitor. So the neuromminadase inhibitors block the release of influenza viruses from infected cells. They do not um kill viruses but they result in the um reduction of the spread of influenza viruses in the respiratory tract. The most commonly used and recommended antiviral that's a neuromminidase inhibitor is also tamir. Um zenamavir and paramavir are also available although less widely available. And the there's one cap dependent endonucleus inhibitor um called blloxir maroxil. We refer to it as blloxir. And this um antiviral in contrast to the neuromminidase inhibitors bloxave inhibits influenza viral replication and is associated with a reduction of influenza viruses in the upper respiratory tract rapidly within 24 hours of treatment. So you can see the table there lists the antiviral drugs with different routes of administration uh and recom different recommended ages for treatment. I'll just say that also tamarin available are given twice daily for 5 days. Paramir is a single intravenous infusion and bloxave is a single oral dose. Next slide. So our antiviral treatment recommendations are focused on prompt treatment of persons with severe disease and those at increased risk of influenza complications. Antiviral treatment is recommended. It has the greatest clinical benefit when started as soon as possible for patients with confirmed or suspected influenza who are hospitalized. And this includes without waiting for testing results if influenza is suspected. And this would be either oral or interic anti- um oscultated uh who are not able to take an oral medication. uh outpatients with complicated or progressive illness of any duration, oral oel tamavir is recommended and outpatients at high risk for influenza complications. Um oral oel tamavvere or oral box are recommended uh if the patient has presented within uh 48 hours of symptom onset. Now for otherwise previously healthy non- high-risk outpatients with confirmed or suspected influenza if they present early um antiviral treatment can be considered with either oral osal tamover or oral blox u but we do really focus on those that are um more severely ill or at high risk for progression um to severe complications of influenza. Next slide. So there are some special pro populations just to say that for pregnant women also tamir is recommended for treatment of influenza um as well as uh in those uh women up to two weeks postpartum. Bloxave is not recommended for treatment of pregnant women or breastfeeding mothers and the reason is that um there's a lack of efficacy or safety data in for blox and pregnant or lactating women. uh in contrast there is substantial global uh evidence of also tamir safety for u pregnancy and birth outcomes there's no concern um for imuninompromised persons because severely imunompromised persons in particular can have prolonged influenza viral replication with emergence of antiviral drug resistance during and after treatment. Uh the monitoring for antiviral resistance is advised with serial with serial collection of respiratory specimens and influenza testing and infection prevention control control precautions are recommended to reduce nocomial transmission rest risk in healthc care uh settings. uh neuromminidase inhibitor treatment is recommended for example with ocel tamavir and blloxir monootherapy is not recommended because of the increased risk of resistance emergence compared to also tamavir now combination antiviral treatment with antivirals of different mechanisms of action for example you could use also tamavir and blloxir this can be considered there are some clinical trials in progress uh next slide So let me just quickly summarize um some of the evidence that we have. So for ocel tamavir randomized controlled trials have shown that ocel tamavir treatment has significant clinical benefit um when started within 36 to 48 hours after illness onset versus placebo or uncomplicated influenza. There's a pulled metaanalysis of five randomized control trials in children when treatment was initiated with oscults. Symptom uh illness duration was reduced by 18 hours overall. When you exclude children that had asthma, there was a reduction in illness duration by 30 hours um with oscult asthma compared to placebo. And overall there was a reduced risk of otitis media by 34%. It's important to also realize there was a increased risk of vomiting in children uh with influenza treated with also tamir versus placebo. Um a pulled metaanalysis a randomized control trials in adults. Um when treatment was started with also tamu tamir within 36 hours of illness onset there was a reduction of illness duration by uh a little more than a day and there was a 44% reduction in the risk of lower respiratory tract complications occurring more than 48 hours after treatment requiring antibiotics. There was also um an increased risk of nausea in adults treated with osal tamavir versus placebo. Next slide please. So there are many different um observational studies of also tamir effectiveness in hospitalized influenza patients. The vast majority of these show uh treatment that there is effectiveness with osel tamir treatment in hospitalized influenza patients and by and um the trend is that the earlier you initiate antiviral treatment with oel tamavir right at the time of hospitalization or shortly thereafter compared to later uh initiation of treatment or no treatment in hospitalized patients with influenza. There is much greater clinical benefit when you start treatment as soon as possible including a reduction in mortality um during the hospitalization or within 30 days of hospitalization. Um also a reduction in the odds of ventilatory support um when treatment is started uh with early within two days of symptom onset which may or may not be possible in a hospitalized patient. Um and so in general um as soon as you start um oeltamir treatment after or at the time of hospital admission there is much greater clinical benefit uh compared to starting treatment later or not at all. Next slide. Similarly for hospitalized pediatric patients there are observational studies reporting u also tamiver effectiveness and the greatest clinical benefit. similar to um in adults who are hospitalized is that when uh treatment is started as soon as possible. Um ideally within two days after symptom onset, but also when you're treated um right at the time of admission or shortly thereafter. You can reduce u the duration of hospitalization. You can reduce the duration of ICU length of stay. you can um reduce the risk of uh readmission um ICU transfer and reduce the risk of the composite outcome of death or ECMO use. Uh next slide. So for bloxave um there are randomized control trials that have demonstrated the efficacy of blloxir for treatment of uncomplicated influenza and in these uh studies in children as well as adolescence and adults. Um these studies have shown that blox treatment has similar clinical benefit to oscultam uh versus placebo um and and in children and adults when blloxir treatment was started within 48 hours after symptom onset. Um and so a single dose of bloxave had a similar um clinical benefit to reducing um influenza signs and symptoms. um uh versus 5 days twice daily of oeltam treatment. Um I in general um this has also been shown for persons with high risk with at least one high-risisk condition. Um so a single dose of blox was equivalent to the clinical benefit of 5 days twice daily of also tamir. Now um two things need to be pointed out. One is that in these trials, bloxave significantly reduced influenza viral RNA levels in the upper respiratory tract at 24 hours and reduced infectious virus detection versus also tamir. Um and then and in a subgroup of patients with influenza Blox significantly reduced um the um the the time to improvement of influenza B symptoms compared to also tamavir. So if the patient is known or suspected to have influenza B uh bloxave is superior to osal tamavvere treatment. Next slide. Um just to close towards the end to show um a concerning trend which is in recent years there's actually been a um there's been low utilization of antiviral treatment in children and adults particularly at higher risk of um uh severe complications. So here are some data from the new vaccine surveillance network in the US NVSN during the 2023 2024 season. These are outpatients at higher risk for influenza complications uh who sought medical care. And you can see that in children aged less than 5 years and those with a high-risisk condition or those both aged less than 5 years and with a high-risisk condition um there was a pretty low proportion of those children who are actually treated with antivirals. So 28 to 39%. Next slide. This slide shows in all ages over a number of years particularly prior to the co 19 pandemic um you can see that there's been a drop off since the co 19 pandemic um in hospitalized uh in antaviral treatment of hospitalized patients in the US kind of in all ages. Next slide. When we look at uh children who are hospitalized or high-risisk outpatients, a similar thing, but the drop off has been even greater in children specifically. You can see that compared to uh prior to the uh co 19 pandemic, there's been a big decline in antiviral treatment of children who are um hospitalized. That's the figure in the left there. And then on the right, two examples, children hospitalized um in a different um uh hospital network, the NVSN, only a little more than 50% had received antiviral treatment. And at the bottom right, you can see that uh children um who presented to an emergency department with lab confirmed influenza, only 32% were prescribed antiviral treatment. Uh next slide. So, self-nowledge check. Which antiviral is recommended for outpatient treatment of influenza in an older adult resident of a long-term care facility who presents with three days of poor appetite, decreased activity, and mild cough and tests positive for influenza. Select the best answer: Zenamavir, Rhyantine, Bloxave, Paramavir, or Ocultam. Next slide. The answer is E. The rationale is that also Tamavir treatment is recommended for patients at high risk for influenza complications. Even if presenting in this patient uh so even if presenting more than two days after symptom onset this patient presented with three days of symptoms. So Rhyantine is not recommended. um uh both amantine and rhymeantine are not recommended for treatment of influenza in the US and the reason is that uh they're only active against influenza A viruses and they're also there is also a very high prevalence of resistance to rhymeant and amantadine. So, Zanamavir, Bloxave, and Pramavir are recommended for treatment of influenza within two days of symptom onset. And this person uh is high risk. They're an adult um long-term care resident uh long-term care facility resident who's been symptomatic for more than two days. And so, this is where also tamar treatment would be recommended. Next slide. So just to uh repeat the key points as I mentioned at the beginning last season was a high severity seasonal influenza epidemic with high morbidity and mortality and a wide range of respiratory non-respiratory complications. Influenza vaccine effectiveness was moderate against in uncomplicated illness as well as severe illness in the US. Influenza activity is increasing in the US. The time to get vaccinated for this season is now for persons aged six months and older who have not received influenza vaccine so far this season. Molecular influenza tests are recommended both for outpatients as well as for hospitalized patients and antiviral treatment is recommended as soon as possible for outpatients at increased risk for complications. So for those presenting within two days of illness onset either also tamavir or bolaxe. For those with progressive or severe disease regardless of the time since illness onset that would be also tamir. And for hospitalized patients with suspected or confirmed influenza also tamavir treatment is recommended as soon as possible. Next slide. So these are some resources um from CDC on influenza prevention and control. Um next slide and thank you for your kind attention and I'll turn it back to Captain Khan. Thank you. >> Thank you presenters. Thank you so much for providing this timely information to our audience. We will now go into our Q&A session. We have time for one question. The question asks um can you clarify when bloxover would be recommended over osult tamavir for treatment of influenza in outpatients and what are the advantages and disadvantage of vexavir versus osult tamavir. >> Yeah that's a great question. So there are some age approval differences in the recommendations. So blloxir treatment is recommended for persons aged five years and older whereas also tamavir is recommended for persons with influenza of all ages. So for a child less than 5 years of age also tamir treatment would be recommended. Blox would be recommended over oelaltam which we have really not been observing in the US. Um but it might be possible for example it could emerge um and also for a patient with known or suspected influenza Blox has much greater efficacy against influenza B compared to also tamavir. Um the advantages of bloxave are there are overall fewer adverse events. it's generally well tolerated and I mentioned that also tamir has a higher risk of nausea in adults uh versus placebo and a higher risk of vomiting in children versus placebo. So a single dose of bloxave um is is not associated with many side effects and and fewer side effects compared to also tamavir. The other thing is for patients um me I think mo every patient would prefer a single oral dose uh bloxave versus uh 5 days twice daily of also tamavir treatment. Um I'll just say the other advantage of um uh blox is that there is a reduction of influenza virus levels in the upper respiratory tract rapidly within 24 hours. But I also should use this opportunity to just mention a few disadvantages. Um and one disadvantage of blox is that u it is associated with emergence of blox resistance up to about 10% in randomized control trials in adolescence and adults. So and in fact we know from other trials in other studies there's a higher frequency of emergence of bolaxive resistance in younger children. Um and this u uh emergence of black severe resistance uh is associated with longer duration of symptoms. And fortunately um transmission of a black severe resistant uh virus from person to person has been very very uh limited. uh it's been reported but it appears to be very uncommon and there's no circulation of blox resistance viruses um or also tamir resistant viruses in the general population um and just to say also tamir would be recommended over bllox for pregnant women um for hospitalized patients for patients with progressive illness and for imunompromised patients and and I'll just stop there by also saying that I uh we need more data for treatment of influenza in hospitalized influenza patients. So severe influenza and for that we need more data for combination uh antiviral treatment for example also tamavir plus bloxave and I'll stop there. Thank you. >> Thank you very much. And a reminder to our audience that if you were unable to ask a question during the webinar today, you may submit your question after the live session by emailing koka at cdc.gov. 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