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2015-2016 Influenza Activity and Clinical Recommendations

Moderators:Ibad Khan

Presenters:Fiona Havers, MD, MHS

Date/Time:February 16, 2016 — 2:00 pm ET

Coordinator:       
Welcome and thank you for standing by. At this time all participants are in a listen-only mode. During the question and answer session please press Star 1 on your touch-tone phone if you’d like to ask a question. Today’s conference is being recorded. If you have any objection please disconnect at this time. I’d like to turn the meeting over to Mr. Ibad Khan. Sir you may begin.

Ibad Khan:         
Thank you Yomi. Good afternoon. I’m Ibad Khan and I’m representing the Clinician Outreach and Communication Activity, COCA, with the Emergency Risk Communications Branch of the Centers for Disease Control and Prevention. I am delighted to welcome you to today’s COCA call: 2015 to 2016 Influenza Activity and Clinical Recommendations.

You may participate in today’s presentation by audio only, via Webinar, or you may download the slides if you are unable to access the Webinar. The PowerPoint slide set and the Webinar link can be found on our COCA Web page at emergency.cdc.gov/coca. That’s emergency.cdc.gov/coca. Click on February 16 COCA call. The slide set is located under call materials.

Free continuing education is offered for this COCA call. Instruction on how to earn continuing education will be provided at the end of the call.

CDC, our planners, presenters and their spouses, partners wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services or commercial supporters. Planners have reviewed content to ensure there is no bias. This presentation will not include any discussion of the unlabeled use of a product or products under investigational use.

At the end of the presentation you will have the opportunity to ask our presenter questions. On the phone dialing Star 1 will put you in the queue for questions. You may submit questions to the Webinar system at any time during the presentation by selecting the Q&A tab at the top of the Webinar screen and typing in your question. Please note that questions are limited to clinicians who would like information on CDC’s current influenza recommendations for vaccination and anti-viral medications. 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 your questions to your healthcare provider.

At the conclusion of today’s session the participant will be able to describe the current status of influenza activity in the United States, discuss the circulating influenza strains seen this season and the implications for clinicians, discuss the use of influenza diagnostic tests and the role in clinical care and discuss anti-viral treatment implications for patients evaluation treatment and testing.

Today’s presenter is Dr. Fiona Havers. Dr. Havers is a Medical Officer for the Influenza Prevention and Control Team within CDC’s National Center for Immunization and Respiratory Diseases. Dr. Haver’s earned a Bachelor’s of Art Degree from Yale University and a Doctor of Medicine from the University of Washington. She completed training in Internal Medicine and Infectious Diseases at the Johns Hopkins University. She also earned in a Masters of Health Science in Epidemiology from Johns Hopkins Bloomberg School of Public Health. Dr. Havers completed the epidemic intelligence service training in the influenza division at CDC and is board certified to practice internal medicine and infectious diseases.

While at CDC Dr. Havers research interests have focused on the epidemiology, prevention, and treatment of influenza. Her research includes studies on influenza vaccine effectiveness and preventing hospitalization, the use of influenza anti-viral medications in outpatient settings, and the impact of seasonal influenza on children with neurologic disorders. Her current primary research focuses on influenza anti-viral treatment as well as influenza vaccine effectiveness.

At this time please welcome Dr. Havers.

Dr. Fiona Havers:
Thank you very much. I really appreciate you having me on this call today.

So today I’m going to give a brief overview of influenza activity this season as well as review our treatment and testing recommendations for influenza. Before we begin I want to make a note on influenza season timing because timing of influenza activity in the United States can be variable.

Most often it peaks between January and March. But during the three most recent influenza seasons activity began relatively early and peaked in last December and January. However, compared to the three most recent seasons the current season activity began to increase in mid-December which is a more typical influenza activity pattern. And since mid- December we have seen activity slowing increasing up until, you know, mid-February where we are now.

Influenza activity is very hard to predict. And how long the season lasts is difficult to know. For the past 13 seasons influenza-like illness activity has remained at or above the national baseline for between one and 19 weeks each season, with an average of 13 weeks. So we expect that activity will probably continue to increase over the coming weeks but it’s difficult to predict how long influenza season will last.

So I will now go over a summary of the 2015-16 influenza activity that we have seen so far. To do this I will use information from our National influenza surveillance systems all of which is publicly available and updated weekly at the Web site shown on this screen. And that’s if you go to cdc.gov/flu/weekly/fluactivtysurv.htm or if you Google FluView you’ll find this Web site.

This map shows the influenza-like illness activity level indicator, which is determined by data reported to ILINet, one of our national flu surveillance systems. For this slide and for many of the subsequent slides this data is current for the week ending February 6, 2016 and is the most recent data that was reported on the FluView website as of last Friday.

So here we see that activity is still relatively low in many parts of the country. Puerto Rico and one state experienced high ILI activity. Two states experience moderate ILI activity. New York City and eight states experienced low ILI activity and 38 states experienced minimal ILI activity and the District of Columbia and one state had insufficient data.

This map shows weekly influenza activity estimates as reported by state and territorial epidemiologists. Widespread influenza activity was reported by Puerto Rico and seven states by this measure. Guam and 17 states reported regional activity and 16 states reported local activity with sporadic activity reported by the District of Columbia-District of Columbia and nine states.

From October to mid-December 2015 influenza activity remained low across most regions of the United States. The current season is show in red on this slide. And as you can see activity began to increase in late December 2015 and continued to increase slowly throughout early 2000-early February 2016.

This slide shows the percent of visits to outpatient providers which were for influenza-like illness or ILI. As I mentioned, the current season is shown in red and activity has been increasing in recent weeks. For the week ending February 6 the proportion of outpatient visits for ILI was 2.5% which is above the national baseline of 2.1%. Other seasons are shown for comparison here, with last year’s season shown in the blue line.

This slide shows positive influenza tests reported to CDC by US public health laboratories. As many of you know every year different influenza types and subtape- subtypes circulate each season. And often we will see one virus predominate.

This season, however, we’ve seen multiple types and subtypes circulating. This slide shows that for influenza A viruses we see both H3N2 viruses, which is shown in red, and H1N1 viruses shown in orange. Although in recent weeks the proportion of viruses that were identified as H1N1 has increased.

In addition there’s also been a significant amount of influenza B viruses which generally belong to two lineages, the Victoria lineage and the Yamagata lineage. These are show in different shades of green on this slide.

The types and subtypes of viruses circulating is important as viruses seem to have varied epidemiologic profiles and tend to affect specific age groups differently.

As you can see here this season so far the largest proportion of viruses identified in children and younger adults have been H1N1 viruses shown in orange. However, we have also seen that H3N2 viruses shown in red have been the most frequently identified viruses among those adults over the age of 64. CDC also tracks laboratory confirmed influenza hospitalizations through FluSurv-NET, which is a multi-state population based surveillance system.

This slide shows the rates of influenza hospitalization per 100,000 persons for this season so far by age group. A cumulative rate for this season of 3.2 laboratory-confirmed influenza hospitalizations per 100,000 populations was reported. The highest rate was among adults 65 years and older shown in green. This is at 10.2 per 100,000 population followed by children age zero to four years. We will see that hospitalization rates are increasing as we would expect as flu activity increases. But as you will see on the next two slides, they are lower than what we’ve seen in previous years. This shows the cumulative hospitalization rate for children under 5 over multiple seasons. This year is shown in orange and last year’s season is shown in green with the 2009 pandemic shown in red.

This slide is similar but it shows the cumulative hospitalization rates for adults 65 and older over multiple seasons. Note that the Y axis is a different scale than on the previous slide.

Compared with last year, which is shown in green, when we saw incredibly high influenza associated hospitalization rates in this age group, this year shown in orange has much lower rates this seasons so far although activity is increasing.

This slide shows the proportion of hospitalized cases with specific underlying medical conditions. Children are shown in green, adults in blue and women age 15 to 44 years of age are shown in purple. Among women in this age group hospitalized with influenza 24% of them were pregnant. And among those hospitalized with influenza more generally 89% of adults and 47% of children had underlying medical conditions. I’d also like to note that while many people hospitalized for influenza have underlying medical conditions. In particular, more than half of the children hospitalized with influenza for whom we had medical record information available did not have an identified medical condition. So we should - clinicians should remember that healthy children are also frequently - are also hospitalized with influenza.

Another group that I would like to highlight is people with neurologic and neuromuscular disorders. Both adults and children with these conditions are at greatly increased risk for severe complications from influenza. And they make up a disproportionate number of those hospitalized with influenza. And they are shown here in the black box.

CDC also tracks pneumonia and influenza mortality. Here in this slide, we show that pneumonia and influenza mortality from the National Center for Health Statistics Mortality Surveillance System.

This slide shows pneumonia and influenza mortality activity for the last several seasons with the area highlighted on the right is the current season activity. Based on NCHS mortality surveillance data available on February 4, 2016, 6.9% of the deaths occurring during the week ending January 23, 2016, which is week three, were due to pneumonia and influenza. And the percentage here was below the epidemic threshold of 7.6% for week three. Note that this data has lagged further back as there is more of a delay than with some of the other surveillance systems.

The CDC also tracks influenza-associated pediatric deaths, which is a reportable condition. The numbers reported for each season show on this slide beginning in 2012 and 13. The total of 11 influenza associated pediatric deaths have been reported during the 2015 influenza season. Two influenza associated pediatric deaths were reported to CDC during week four. One death was associated with an influenza A H1N1 virus that occurred during week two and one death was associated with an influenza B virus and occurred during week four.

So the information I just presented is from our National influenza surveillance systems. However I did want to draw clinicians’ attention to the fact that in recent weeks CDC has received reports from several states of severe respiratory illnesses among young to middle aged adults. A number of these patients required intubation and fatalities have been reported. Most of these persons were infected with influenza A H1N1 pandemic viruses. And some of these patients reportedly tested negative for influenza by rapid influenza diagnostic tests. Their influenza diagnoses were made later with molecular assays. And most of these patients were reportedly unvaccinated.

Earlier this month CDC issued a health advisory through the Health Alert Network or HAN urging rapid anti-viral treatment of very ill and high risk – and high risk suspect influenza patients without waiting for testing. With the HAN and now with these continued reports we wanted to bring these to the attention of clinicians as we know that H1N1 virus infection in the past has caused severe illness in some children and young and middle-aged adults. In addition we want to remind clinicians to consider influenza as a diagnosis and to start antiviral treatment of severely ill and high risk patients if influenza is suspected or confirmed. We will go over anti-viral recommendations in more detail in a moment. I also want to remind clinicians that in a negative rapid influenza antigen diagnostic test does not exclude a diagnosis of influenza and that treatment should not be delayed for even for a few hours to wait for the results of testing. We will also discuss testing recommendations in a moment as well.

In addition to prompt treatment, it is not too late to think about influenza vaccination as a way of protecting your patients. Last year there was a mismatch between the vaccine virus strains and the circulating influenza viruses causing the vaccine to be not as effective. Fortunately, however, we are not seeing this this year. Most of the influenza viruses characterized from October to February are antigenically similar to the vaccine virus strains recommended for inclusion in this year’s Northern hemisphere vaccine although we don’t have any interim vaccine effectiveness estimates available yet.

We do want to remind clinicians that influenza vaccination is the best way to prevent influenza infection and that clinicians should continue to vaccinate patients this season for as long as influenza viruses are circulating.

Annual influenza vaccination is recommended for all persons six months and older. So for the influenza seasonal activity to date activity began to increase in late December and is continuing to increase slowly through early February 2016. Influenza A H1N1 viruses are currently the most frequently identified viruses. And we have received reports of severe disease in some children and young and middle-aged adults. We expect activity to continue to increase but it is difficult to say for how long.

As I mentioned before a number of the patients that had severe influenza illness this season reportedly had rapid influenza diagnostic tests. I’m now going to review testing guidance for influenza. Not all patients need to be tested for influenza. However, if it will inform or influence clinical management testing is recommended in the following groups of people: high risk outpatients who present with acute respiratory illnesses within five days from illness onset, which is the time when most patients are shedding virus; hospitalized patients with fever and acute respiratory illness anytime from illness onset; elderly and infants with sepsis; and immuno-compromised patients with ARI anytime from illness onset because patients in this group may have prolonged viral shedding.

Before ordering an influenza test, clinicians should ask themselves - will the result change clinical care?

We have an algorithm which is also on our Website which goes through the different types of tests and should help guide clinician judgement in terms of whether or not an influenza test should be ordered. First it’s obvious to ask does the patient have clinical signs and symptoms compatible with influenza? If not, influenza virus testing is probably not indicated. If they do, will the results of influenza virus testing change the clinical care of the patient or influence clinical practice for other patients in terms of infection control and other issues? If the answer is yes, consider influenza virus testing. However the type of test that is used is very important. There are a number of diagnostic tests available. There is viral cell culture, rapid sale culture of shell vial and cell mixtures. There is immunofluorescence testing including DFA or IFA antibody staining. One that is increasingly used is RT-PCR and other molecular assays. And then there are rapid influenza diagnostic tests. And here I’m referring to antigen-based testing. There are some new rapid molecular assays that are available in a short period of time but when I refer to rapid influenza diagnostic tests I’m referring to the antigen based ones which are the most commonly used.

Now a word of caution about rapid influenza diagnostic tests or rapid tests. They have a number of advantages. The results are available in 15 to 20 minutes often. They can be done as point of care testing. However they can be quite insensitive. There are different studies that have lifted the sensitivity of rapid tests compared with PCR but the sensitivity can be as low as 10% but is usually in the range of 40 to 70 percent. In addition when the prevalence of circulating influenza is low specificity is reduced so some false positives can occur. But in general false negatives for rapid tests can be quite frequent.

On the right-hand side there’s an algorithm for how to interpret a rapid influenza diagnostic test. If it’s positive, especially during influenza season or when there’s known influenza circulating in the community, influenza virus infection is likely and a clinician can initiate anti-viral treatment for influenza if clinically indicated. However, if a rapid-test is negative, you cannot rule out influenza virus infection. The clinician should use clinical signs, symptoms, history, examination, information on local influenza activity in the community to decide if anti-viral treatment is indicated. Do not rely exclusively on a negative rapid influenza diagnostic tests for clinical decision-making or for public health decisions, including identifying influenza outbreaks or for decisions on infection control measures. If the patient who has suspected influenza has a negative rapid test, you can consider additional influenza testing if indicated. But this should not necessarily be used as the basis for a decision to withhold treatment.

We do know that clinicians are heavily influenced by the results of rapid influenza diagnostic tests in terms of how they inform anti-viral use. In a survey of outpatient providers the use of rapid influenza diagnostic tests in 2010, 80 to 90 percent used RIDTs to confirm influenza before antivirals were prescribed.

As I mentioned before if a patient does have influenza and the rapid test if positive that’s fine. However, clinicians who rely entirely on - rely on rapid influenza diagnostic tests may be missing a large number of people with influenza.

I’m going to discuss our treatment recommendations among high risk patients in more detail later. But here I’d like to just say a few words about testing in high risk out-patients who present with acute respiratory illness. We do know that many of them come to clinic more than two days after illness onset. And anti-viral drugs are used less commonly than antibiotics even among patients with influenza.

As I just demonstrated rapid influenza diagnostic tests are the preferred diagnostics - are the most widely used diagnostics. And clinicians do treat based on these test results. But rapid influenza tests often give false negatives. And many high risk patients that may benefit from treatment may be missed.

Now that was discussing rapid influenza diagnostic testing among out-patients. What about in hospitalized patients? In a survey of diagnostic tests performed in hospital laboratories, they looked at 240 different hospital laboratories. Sixty-seven percent relied only on rapid influenza diagnostic tests to diagnose influenza. Twenty-six percent reported the availability of molecular diagnostic assays for the detection of influenza. And these are much more sensitive assays. And testing for other viruses was even less common.

This slide here shows the used of the type of testing in different hospitals from this survey. In the blue bars is from a 2006, 2007 survey pre-2009 pandemic. And the red bars show the kind of testing available in 2012-13. As you can see rapid tests are still the most commonly used in hospitals. The use of molecular assays has increased but still less than 1/3 of hospitals have access to these type of tests. Viral culture and DFA or IFA tests have decreased somewhat in recent years and serology tests are rarely used as they often do not give information in a timely enough manner to influence clinical care.
We do know that testing and hospitalized ARI patients does influence clinical care. In recent seasons most hospitalized patients with positive influenza tests were treated in the US. However, testing for influenza was not common and tests with the results available quickly were used more. As I mentioned, rapid tests were still used by most hospital laboratories in 2012-13. And anti-viral treatment is strongly associated with influenza testing and empiric treatment was uncommon.

So we do want to remind clinicians that influenza should be high on the list of possible diagnoses for ill patients. A negative rapid influenza antigen diagnostic test does not exclude a diagnosis of influenza. In all hospitalized patients, in all high risk patients with suspected or confirmed influenza should be treated as soon as possible without waiting for a confirmatory test. In many situations, empiric treatment is the best option.

Now I’m going to discuss in more detail our recommendations for antiviral use. Evidence from current and previous influenza seasons suggest that anti-viral drugs are underutilized. There appears to be low awareness of antiviral recommendations. And there’s a wide range in the perception about antiviral effectiveness.

As I mentioned before many clinicians may require a positive diagnostic test before prescribing. But the results of these rapid tests may not be accurate. And some clinicians may not prescribe after the 48 hour window that is optimal for treatment.

One study showed that less than 1/5 of patients who were at high risk for influenza complications and presented to care with an acute respiratory infection within two days of symptom onset, meaning the time period when anti-viral treatment is most beneficial. Less than 1/5 received a prescription for antivirals. But yet a much higher proportion received a prescription for an antibiotic. This study demonstrates that clinicians are still more likely to prescribe antibiotics rather than anti-viral medications to outpatients with influenza including to high risk patients who would benefit from early empiric antiviral treatment.

Now I just want to remind you that when we’re talking about antiviral medications, there are currently three antiviral medications that are used for treatment for influenza in the United States. The most commonly used is oral Oseltamivir which is recommended for treatment for all ages and can be used for pre-chemoprophylaxis for those aged 3 months and older. The next is inhaled Zanamivir which is recommended for treatment for those aged 7 and older and chemoprophylaxis for ages 5 and older. And a relatively new drug is IV Peramivir, which was approved in December 2014 for the treatment of acute uncomplicated influenza in persons 18 years and older. IV Peramivir comes in a 600 milligram dose. It’s usually infused over 15 to 30 – to 30 minutes.

In general these medications are well tolerated. But I will review some of the side effects. For Oseltamivir has been associated with a slightly increased risk of nausea and vomiting over placebo. But - however this is mild and transient and it generally improved when taken with food. Inhaled Zanamivir has been associated with cases of bronchospasm that were reported during the post-marketing phase. It is not recommended for persons with underlying airways disease such as asthma and COPD. In IV Peramivir, did show a slightly increased risked of diarrhea and neutropenia over placebo. However in many cases, the potential benefits do outweigh the risks.

As you will see, our recommendations focus on the most severely ill and those at high risk of severe complications. Unfortunately, for those that are high risk for serious complications, there are no randomized control trials available that were powered to detect serious outcomes in these patient groups. Thus our - the evidence base for these guidelines includes observational studies and meta-analyses of anti-viral effectiveness. And CDC’s antiviral recommendations are common to ACIP, IDSA and the American Academy of Pediatrics.

For all patients in the following categories with suspected or confirmed influenza should be treated as soon as possible without waiting for confirmatory influenza testing: hospitalized patients, patients with severe complicated or progressive illness, and patients at risk for complications from influenza either outpatient or hospitalized. Clinical judgment on the basis of the patient’s disease severity and progression, age, underlying conditions, likelihood of influenza and time since onset of symptoms is important when making antiviral treatment decisions for high risk patients.

Antiviral treatment may be considered for any previously healthy symptomatic outpatient not at high risk with confirmed or suspected influenza on the basis of clinical judgement.

Persons as high risk for influenza complications include children less than 2 years of age, adults 65 years and older, pregnant and post-partem women within two weeks after delivery, American Indians and Alaska natives, persons who are morbidly obese, residents of long term care facilities, immunosuppressed persons, and children less than 19 years of age who are receiving long term aspirin therapy. In addition persons with underlying medical conditions including chronic pulmonary, cardiovascular, renal, hepatic, hematologic, and metabolic disorders including diabetes or neurologic and neuro developmental conditions are all at increased risk for influenza complications.

When indicated, antiviral treatment should be started as soon as possible after illness onset. Ideally treatment should be initiated within 48 hours of symptom onset. It should not be delayed even for a few hours to wait for the results of testing. And as I mentioned before a negative rapid influenza diagnostic test does not exclude a diagnosis of influenza.

During influenza season especially, healthcare providers should advise high risk patients to call their provider promptly if they have symptoms of influenza. It may be useful for providers to implement phone triage lines to enable high risk patients to discuss their symptoms over the phone and to facilitate early initiation of treatment when feasible. An antiviral prescription can be provided without testing and before an office visit.

Although antiviral treatment is most beneficial when initiated promptly within 48 hours of symptom onset, antiviral treatment initiated after 48 hours can still be beneficial in some patients. Observational studies of hospitalized patients suggest that treatment might still be beneficial when initiated four or five days after symptom onset. And observational data in pregnant women has shown that antiviral treatment can provide benefits when started three to four days after onset. In addition there was a randomized placebo controlled study suggesting that clinical- which suggested that clinical benefit when Oseltamivir was initiated 72 hours after illness onset among febrile children with uncomplicated influenza.

Now for outpatient treatment any neuraminidase inhibitor may be used. Most commonly this is a five day course of Oseltamivir or inhaled Zanamivir. Single dose IV Peramivir may be considered in people who have difficulty taking the available oral or inhaled medications because of nausea, difficulty swallowing pills, or significant reactive airway disease or COPD. Oral Oseltamivir is preferentially recommended for pregnant women. Among hospitalized patients treatment with oral or enterically administered Oseltamivir is recommended. Limited data suggests that Oseltamivir administrated by oral or nasal gastric tubes is well absorbed in critically ill influenza patients including those in the intensive care unit on continuous renal replacement therapy or on ECMO. Inhaled Zanamivir is not recommended because of the lack of data for use in patients with severe influenza disease. And there is currently insufficient data regarding the efficacy of IV Peramivir for hospitalized patients. Of note although the normal treatment course for influenza is five days for Oseltamivir and Zanamivir, for treatment for patients who remain severely ill after five days of treatment, longer treatment courses may be considered.

For patients who cannot tolerate or absorb oral Oseltamivir because of suspected or known gastric stasis, malabsorption, or GI bleeding, the use of IV Peramivir or investigational IV Zanamivir should be considered. However if Peramivir is used in severely ill patients the single dose should not be given. And for severely ill patients the adult dose is 600 milligrams IV once daily for five days is recommended with a minimum of five days duration.

Regarding the treatment of hospitalized patients, there is sometimes a concern regarding Oseltamivir resistance. Some influenza viruses may become resistant to Oseltamivir and Peramivir during antiviral treatment with one of these agents yet these often remain susceptible to Zanamivir. Investigational use of IV Zanamivir should be considered for treatment of severely ill patients with Oseltamivir resistant virus infection. However, I would like to note that the most common situations when patients are failing to improve on Oseltamivir this is not a result of Oseltamivir resistance but more a result of the underlying disease process. We most often see Oseltamivir resistance develop in very immunocompromised patients for example in patients with stem cell transplants who have prolonged shedding of the virus. If you’re concerned about Oseltamivir resistance there’s more information on our Web site regarding this.

One other thing to note, I just want to make a brief comment about antibiotics and bacterial infections in influenza patients. As all of you know antibiotics are not effective against influenza. And several reports suggest that inappropriate use of antibiotics is common among patients with influenza. However bacterial infections can occur as a complication of influenza and so should be considered and appropriately treated if suspected.

I also want to draw attention to institutional outbreaks. Outbreaks that occur in long-term care facilities, nursing homes or other living facilities that house high risk persons can have devastating outcomes for the vulnerable persons that live in those institutional settings. Aggressive infection control measures are necessary to stop outbreaks in these settings. And the use of antiviral chemoprophylaxis, along with a number of other measures to control outbreaks among high risks persons, in institutional settings is recommended. And we recommended prophylaxis for all residents regardless of their vaccination status for unvaccinated healthcare personnel. And we recommend generally for a minimum of two weeks continuing at least seven days after the last known case is identified. I will also include a link at the end of this talk to more information about dealing with outbreaks in institutional settings.

So for a summary of our antiviral recommendations early empiric antiviral treatment is recommended for suspected or confirmed influenza among the following: hospitalized patients, patients with severe or progressive illness, and any patient at a high risk for complications from influenza. Decisions about antiviral treatment should not wait for laboratory confirmation of influenza. And the clinical benefit is greatest when influenza treatment is initiated early. But there is evidence that treatment initiated later than 48 hours after onset can still be beneficial for some patients.

If we go back to what we discussed at the beginning of this call influenza activity this season is increasing. It started a little bit later than it has in the previous several seasons but we are seeing an increase in influenza activity in recent weeks. Given that, vaccination is still possible and we do recommend that clinicians still offer influenza vaccination to their patients while influenza viruses are circulating.

It’s been a mixed season so far but H1N1 viruses are now the most frequently detected, although we are still seeing H3N2 and Influenza B viruses. Especially given the frequency with which we’re seeing H1N1 viruses, we can expect to see some severe disease in children and young and middle aged adults. And we would encourage clinicians to have a high level of suspicion for influenza if they see symptoms compatible with influenza in patients in these age groups. And as we noted previously a number of people presenting with severe influenza had rapid negative tests. And decisions regarding treatment should not be made on the basis of a negative rapid influenza diagnostic test.

So here I’ve posted a number of Web sites for additional information. There is a summary of influenza antiviral treatment recommendations for clinicians. There is also guidance for clinicians on the use of rapid influenza diagnostic tests including - this page includes a number of the algorithms that I included in this talk. There is also interim guidance for influenza outbreak management in long term care facilities which goes into much more detail about other measures besides chemoprophylaxis that should be used in this setting. We also have further information about preventing seasonal influenza spread within healthcare settings. And for further more detailed information about the drugs that we discussed on today’s call there is a link to the FDA flu antiviral drug information. I’ve also included a link to the American Academy of Pediatrics information on influenza in children.

So I’d like to thank a number of people including Angie Campbell and Alicia Fry within the influenza Division and our Communications Team who’ve been very helpful. And I’d like to thank you all very much for your time today. And I’m happy to take your questions.

Ibad Khan:         
Thank you Dr. Havers for providing our COCA audience with such a wealth of information.

We will now open up the lines for the question and answer session. Questions are limited to clinicians who would like information on CDC’s current influenza recommendations for vaccination and antiviral medications. 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 your questions to your healthcare provider.

Remember when asking a question please state your organization and also remember you can submit questions to the Webinar system as well.

Operator before we start with questions on the phone there is a question on the Webinar system that I would like the presenter to address. The question is should we still be using Amantadine for influenza?

Dr. Fiona Havers:
The short answer to that is no. Most of the current circulating viruses are generally resistant to the Adamantanes. The Adamantanes include Amantadine and Rimantadine. And since, pretty much since 2009 we have recommended not using those for the treatment of influenza. The only recommended treatments currently are neuraminidase inhibitors which include Oseltamivir and Zanamivir and Peramivir because the current circulating viruses are likely to be resistant to Amantadine.

Ibad Khan:         
Thank you Dr. Havers.

Dr. Fiona Havers:
That’s an excellent question and it’s a – it’s a good one to remind clinicians about that.

Ibad Khan:         
Thank you. Operator you may open the lines for questions.

Coordinator:       
Thank you. As a reminder if you’d like to ask a question please press Star 1 and record your name. Make sure your phone is unmuted and record your first and last name clearly at the prompt. To withdraw your request please press Star 2. Again if you’d like to ask a question please press Star 1 and record your name. One moment speakers to see if we have any questions.

Ibad Khan:         
Dr. Havers while we’re waiting on the questions on the phone line, there is a question on the Webinar system that we would like to address.

Dr. Fiona Havers:
Okay.

Ibad Khan:         
The question is when patients present non-remarkable history what should be the criteria for choosing Zanamivir or Oseltamivir?

Dr. Fiona Havers:
I think that - I mean they’re both – both of those medications can be used for the treatment of outpatients.

Again if they do have any underlying chronic pulmonary disease such as COPD or asthma inhaled Zanamivir is not recommended and we would recommended Oseltamivir in that – in that case. We’d also recommend, preferentially recommend, Oseltamivir for pregnant women. But really either of those can be used. It can depend on patient preference. One is an oral medication. Another is an inhaled medication.

Ibad Khan:         
Thank you Dr. Havers. Operator do we have any questions on the line?

Coordinator:       
We have one question from the phone. It comes from Tonya Jones. Please state your organization.

Tonya Jones:       
Capella University.

Coordinator:       
Please ask your question.

Tonya Jones:       
Yes. If the rapid results are negative then and if the patient is presenting clinically as –as having flu-like symptoms do you have any recs regarding serum testing that comes back positive for the patient that - that rapid results are negative?

Dr. Fiona Havers:
Well, the situation where you have a patient who comes in and they look like they have flu but the rapid test is negative is one really where clinical judgement comes in. We don’t generally recommend serum testing but you can do sort of acute and convalescent serum to see if someone has been infected with flu. But those results take a very long time to come back and they’re not generally clinically relevant. If there is a - if there’s a serious question about the diagnosis for example in a hospitalized patient one could consider additional testing. But generally we wouldn’t recommend serum based testing. We would probably, if it was available, encourage molecular testing with PCR-based assays, because those generally tend to be much more sensitive than the rapid influenza diagnostic tests.

However in general if you have a high risk patient who’s at-risk who presents with influenza like symptoms during influenza season and would potentially benefit from antiviral treatment, one could go ahead and empirically treat regardless of the negative rapid test. We don’t want people to - doctors or other clinicians to look at a negative test and say oh that person doesn’t have flu even though they look like they have flu and decide to withhold treatment based on that. You don’t need to have influenza confirmed to treat empirically with antiviral drugs if they’re clinically indicated and the patient’s clinical picture is consistent with flu. A rapid test may be helpful in confirming a diagnosis but it does not rule out an influenza diagnosis if it – if it comes back negative just because of the low sensitivities of many of the assays. That’s a good question though.

Tonya Jones:       
Thank you.

Coordinator:       
Thank you speakers. We have one other question. It comes from Elizabeth Meade. Please state your organization.

Elizabeth Meade:
The University of Redlands Student Health Center.

Coordinator:       
Please ask your question.

Elizabeth Meade:
Hi. I work at a - a university student health center. Mostly undergraduate students so between the ages of 18 and 22 with some graduate students. We are mostly a residential campus which means, you know, most of our undergraduate students live here on campus and dorms. We have about 2500 students on campus at any given time plus maybe 800 or so staff members.

We - I’ve - you know, I’ve started seeing some increased flu activity and we are a sentinel provider for the – for the California Department of Public Health so we do some testing for them which is actually very helpful for us to know which viruses are circulating and to kind of detect viral activity. My question is I know you talked a lot about starting antiviral medications for people at high risk for complications of flu. I have a lot of students who come in really wanting their Z-pack when they have cold symptoms or flu symptoms.

I have actually been a little bit more willing to prescribe antivirals just because I know that we’re, you know, seeing cases of flu. And then we have had some positive rapid flu tests although I do, you know, if I have someone who has a negative rapid flu and they have flu symptoms and they have something like asthma I would definitely be more likely to prescribe them Oseltamivir or something like that.

So my question is even if they’re not at high risk of complications from flu if they’re just in an outpatient setting would you recommend starting people on antiviral medication if they have flu-like symptoms?

Dr. Fiona Havers:
That’s a - that is a great question because we know that many, many patients that go to their clinicians during influenza season have influenza but they end up with a Z-pack, which doesn’t benefit them because they have a virus. So, you know, we really want to strongly encourage clinicians to treat high risk patients with antiviral medications. But it is certainly okay to treat non-high-risk patients with antiviral medications if the clinical picture fits and it’s consistent with your clinical judgment. I certainly think for many patients with influenza they’re more likely to benefit from an antiviral medication than an antibiotic when they have - when they’re infected with a virus. And so I think - I mean, I think it gives clinicians an alternative as something to offer patients if during flu seasons and they have flu symptoms they are more likely to benefit from an antiviral medication if they have influenza than they will with an antibiotic. And I think, you know, for many college students the duration of symptoms may be shortened and they might be appreciative of receiving an antiviral mediation.

So while we - while we’re - we do recommend that it’s high risk patients that that our antiviral recommendations target, we say that it can be considered for healthy - like otherwise healthy outpatients with uncomplicated influenza if the clinician decides that it may clinically benefit them. So that’s a very good question though. We would definitely like to have fewer Z-packs prescribed for acute respiratory infections which are almost - which are most likely viral during influenza season.

And not just influenza. There’s also RSV and other things which frequently get treated - over-treated in the outpatient setting with antibiotics. Thank you for that question.

Coordinator:     
I show no other questions in the queue.

Ibad Khan:         
Dr. Havers while we’re waiting to see if there’s any other questions coming in through the phone line I do have a couple of questions also about patients with increased risk of complications that I would like to kind of sum up in one question and have you address.

Dr. Fiona Havers:
Okay.

Ibad Khan:         
So both questions are asking for rationale why two patient populations are generally considered at an increase for complications. One pertains to the Native American population and the other for the morbidly obese.

Dr. Fiona Havers:
Okay those are both great questions. There have been a number of epidemiologic studies that have shown that American Indian and Alaska Native populations are at increased risk for serious influenza complications. There is some suggestion that their increased risk may be confounded by other things that are associated for example, with increased levels of poverty or decreased vaccination rates or other things.

But that recommendation is based on prior epidemiologic evidence that they are potentially at more risk. But as with all these recommendations, these recommendations are continuously undergoing review but it’s based on epidemiologic studies. The morbidly obese one is a great point and it’s something that we should remind people about particularly in the seasons where we see H1N1 circulating.

Morbid obesity came out at a very strong risk factor for serious complications of influenza during the 2009 pandemic. The proportion of people hospitalized that were intubated, in the ICU or that died was clearly associated with being morbidly obese. And so it’s something that even if you have someone who’s other - appears otherwise healthy if they get influenza and they’re obese and they’re very obese with BMI of 40 – of 40 and above they are at increased risk for severe complications.

We’re not 100% sure of the mechanism of that. Often it may be a mechanical thing. They’re not able to protect their airway as much. Clearing the infection from their lungs may be more difficult or the fact that they’re obese may be highly associated and interact with other chronic medical conditions that they may have, such as diabetes. But those are two groups that are currently considered at higher risk for influenza complications.

Ibad Khan:         
Thank you Dr. Havers. Operator do we have any questions on the phone line?

Coordinator:       
We have an additional question. It comes from Ryan Hickman. Please state your organization and proceed with your question.

Ryan please check your mute button.

I show no other questions.

Ibad Khan:         
Thank you operator. On behalf of COCA I would like thank everyone for joining us today with a special thank you to our presenter Dr. Havers.

We invite you to communicate with our presenter after the Webinar. If you have additional questions for today’s presenter please email us at coca@cdc.gov. Put the February 16 COCA Call in the subject line of your email and we will ensure that your question is forwarded to the presenter for a response. Again that email address is C-O-C-A@cdc.gov.

The recording of this call and the transcript will be posted to the COCA Web site at emergency.cdc.gov/coca within the next few days.

Free continuing education is available for this call. Those who participated in today’s COCA conference call and would like to receive continuing education should complete the online evaluation by February 29, 2016 using Course Code WC2286. For those who will complete the online evaluation between March 1, 2016 and March 1, 2018 use Course Code WD2286.

All continuing education credits and contact hours for the COCA conference calls are issue - issued online through TCE Online, the CDC Training and Continuing Education Online System at www.cdc.gov/tceonline.

To receive information on upcoming COCA calls subscribe to COCA by going to the COCA Web page at emergency.cdc.gov/coca and clicking on Join the COCA Call Mailing List link. Join us for our next COCA call on February 23rd at 2:00 PM Eastern Time on Heart Disease as a Health Threat. Get detailed information about this call by visiting the COCA Web page at emergency.cdc.gov/coca.

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Coordinator:       
Thank you for your participation. You may disconnect at this time. Speakers please stand by for the post conference.

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