CDC Clinician Outreach and Communication Activity (COCA) Webinar 2013-2014 Influenza Season: Updates and Recommendations for Clinicians Frequently Asked Questions

The January 23, 2014, COCA webinar featured Angela Campbell, MD, MPH, FAAP, Medical Officer from CDC’s National Center for Immunization and Respiratory Diseases, Epidemiology and Prevention Branch in the Influenza Division. This document contains a summary and consolidation of the most frequently asked questions and comments from the webinar, along with responses based on CDC recommendations and guidance.

ANTIVIRAL THERAPY/CLINICAL MANAGEMENT

Is antiviral therapy recommended for patients who are not high risk?
Clinicians can use their clinical judgment and consider antiviral treatment for previously healthy outpatients with confirmed or suspected influenza who are not in one of the high-risk groups, if treatment can be initiated within 48 hours of illness onset.

When do you recommend doing prevention with antivirals and for how long?
CDC does not recommend widespread or routine use of antiviral medications for prevention (chemoprophylaxis) so as to limit the possibilities that antiviral resistant viruses could emerge. Indiscriminate use of chemoprophylaxis might promote resistance to antiviral medications, or reduce antiviral medication availability for treatment of persons at higher risk for influenza complications or those who are severely ill.

Annual influenza vaccination is the best way to prevent influenza because vaccination can be given well before influenza virus exposures occur, and can provide safe and effective immunity throughout the influenza season.

For some persons, an emphasis on close monitoring and early initiation of antiviral treatment is an alternative to chemoprophylaxis after a suspected exposure.

However, chemoprophylactic use of antiviral medications to control outbreaks among high-risk persons in institutional settings is recommended. For example, when influenza is identified as a cause of a respiratory outbreak among nursing home residents, use of antiviral chemoprophylaxis for all exposed or at-risk residents and for unvaccinated health care personnel is recommended. For vaccinated staff, antiviral chemoprophylaxis can be administered up to 2 weeks following influenza vaccination. For more information on the control of institutional outbreaks, please see the IDSA guidelines web site.

Here are some additional instances when antiviral medications can be considered for chemoprophylaxis to prevent influenza: Prevention of influenza in persons at high risk of influenza complications during the first two weeks following vaccination after exposure to an infectious person.

Prevention for people with severe immune deficiencies or others who might not respond to influenza vaccination, such as persons receiving immunosuppressive medications, after exposure to an infectious person.

Prevention for people at high risk for complications from influenza who cannot receive influenza vaccine due to a contraindication after exposure to an infectious person.

To be effective as chemoprophylaxis, an antiviral medication must be taken each day for the duration of potential exposure to a person with influenza and continued for 7 days after the last known exposure. For persons taking antiviral chemoprophylaxis after inactivated influenza vaccination, the recommended duration is until immunity after vaccination develops (antibody development after vaccination takes about two weeks in adults and can take longer in children depending on age and vaccination history).

We are a college health service. We have several students who have tested positive for influenza A. Should we be treating their roommates with Tamiflu?
No, preventive treatment is not recommended in most circumstances. Close monitoring and early initiation of treatment if symptoms develop is recommended.

When is it indicated to use dual neuraminidase inhibitor therapy?
Use of therapy with more than one neuraminidase inhibitor is not recommended. It is possible that some influenza viruses may become resistant to oseltamivir during antiviral treatment and remain susceptible to zanamivir; this has been reported most often for influenza A H1N1 viruses. Resistance of influenza viruses to antiviral drugs can also occur spontaneously, with no known exposure to antiviral medications. If a hospitalized patient treated with oseltamivir manifests progressive lower respiratory symptoms, resistant virus should be considered. In view of the limited alternatives, CDC recommends that investigational use of intravenous (IV) zanamivir should be considered for treatment of severely ill patients with oseltamivir-resistant virus. Oseltamivir should not be stopped until IV zanamivir can be initiated. Oseltamivir and zanamivir, either inhaled or IV, should not be administered together.

What should be an extended duration of oseltamivir therapy: 10 days, 14 days or longer?
The recommended treatment course for uncomplicated influenza is two doses per day of a neuraminidase inhibitor medication for 5 days; however, the optimal duration and dose are uncertain for severe or complicated influenza. Treatment regimens might need to be altered to fit the clinical circumstances. For example, clinical judgment should be the guide regarding the need to extend treatment regimens longer than 5 days for patients whose illness is prolonged. Critically ill patients with respiratory failure can have prolonged influenza viral replication in the lower respiratory tract.

Clinical judgment and virologic testing of lower respiratory tract specimens by real-time reverse transcription-polymerase chain reaction (rRT-PCR) should guide decisions to consider treatment regimens longer than 5 days for patients with severe and prolonged illness. For patients with lower respiratory tract disease, lower respiratory tract specimens, such as bronchoalveolar lavage fluid or endotracheal aspirates, are preferred; an oropharyngeal (throat) swab may be collected if lower respiratory specimens are not available. Testing of lower respiratory tract specimens may yield the diagnosis when testing of upper respiratory tract specimens is negative. Multiple respiratory tract specimens collected on different days should be tested if influenza virus infection is suspected but a definitive diagnosis has not been made.

Longer treatment regimens might be necessary in immunosuppressed persons who may have prolonged influenza viral replication. Such patients are at risk of developing antiviral-resistant virus.

Is there benefit to administering a higher dose of oseltamivir for treatment of influenza in severely ill hospitalized patients? In morbidly obese patients?
A higher dose of oral or enterically administered oseltamivir has been recommended by some experts (e.g., 150 mg twice daily in adults with normal renal function) for treatment of influenza in immunocompromised patients and in severely ill hospitalized patients. However, oral or enterically administered oseltamivir has been reported to be adequately absorbed in critically ill adults, with standard doses producing therapeutic blood levels, and limited data suggest that higher dosing may not provide additional clinical benefit. Studies indicate that the exposure to oseltamivir carboxylate (the active metabolite of oseltamivir) is similar between obese and non-obese subjects for both 75 mg and 150 mg doses given twice daily.

What is the correct dosage of oseltamivir for patients with impaired renal function?
Serum concentrations of oseltamivir carboxylate, the active metabolite of oseltamivir, increase with declining renal function. For patients with creatinine clearance of 10--30 mL per minute, a reduction of the treatment dosage of oseltamivir to 75 mg once daily and in the chemoprophylaxis dosage to 75 mg every other day is recommended. Treatment or chemoprophylaxis dosing recommendations have been proposed for patients undergoing routine renal dialysis treatment but are based on limited pharmacokinetic data.

One of the presenters had mentioned using IV Peramavir. Is it truly not available?
At this time, IV peramivir is not available via clinical trial, compassionate use, or Emergency Use Authorization.

What about use of steroids in the management of H1N1?
Systemic steroid therapy is not recommended for management of H1N1. Systemic glucocorticoid treatment is associated with prolonged viral replication and secondary bacterial and fungal pneumonia, and higher mortality, and should be avoided. However, glucocorticoid treatment can be continued for patients receiving long-term glucocorticoid therapy for other conditions and can be administered for certain complications.

LABORATORY TESTING

When should laboratory testing occur?
If the patient has clinical signs and symptoms compatible with influenza and results of influenza virus testing may change clinical care of the patient, influenza virus testing should be considered. Influenza testing is recommended for hospitalized patients with suspected influenza. However, empiric antiviral treatment should be initiated as soon as possible without the need to wait for any influenza testing results.

Clinicians should understand that negative results of influenza testing do not exclude influenza virus infection, especially if the time from illness onset to collection of respiratory specimens is more than 5 to 7 days, or if upper respiratory specimens were tested and the patient has lower respiratory tract disease.

If influenza is suspected, testing of clinical specimens collected from different respiratory sites can be done (e.g. upper and lower respiratory tract) and can be collected on more than one day to increase likelihood of influenza detection; intubated patients should have endotracheal aspirate specimens tested if influenza is suspected, but confirmed definitive diagnosis has not been made.

What is the recommendation for re-testing after Tamiflu has been completed, particularly in those patients who remain very ill and in the hospital?
The recommended treatment course for uncomplicated influenza is two doses per day of a neuraminidase inhibitor medication for 5 days; however, the optimal duration and dose are uncertain for severe or complicated influenza. Treatment regimens might need to be altered to fit the clinical circumstances. For example, clinical judgment should be the guide regarding the need to extend treatment regimens longer than 5 days for patients whose illness is prolonged. Critically ill patients with respiratory failure can have prolonged influenza viral replication in the lower respiratory tract.

Clinical judgment and virologic testing of lower respiratory tract specimens by real-time reverse transcription-polymerase chain reaction (rRT-PCR) should guide decisions to consider treatment regimens longer than 5 days for patients with severe and prolonged illness. For patients with lower respiratory tract disease, lower respiratory tract specimens, such as bronchoalveolar lavage fluid or endotracheal aspirates, are preferred; an oropharyngeal (throat) swab may be collected if lower respiratory specimens are not available. Testing of lower respiratory tract specimens may yield the diagnosis when testing of upper respiratory tract specimens is negative. Multiple respiratory tract specimens collected on different days should be tested if influenza virus infection is suspected but a definitive diagnosis has not been made.

It is possible that some influenza viruses may become resistant to oseltamivir during antiviral treatment and remain susceptible to zanamivir; this has been reported most often for influenza A H1N1. Resistance of influenza viruses to antiviral drugs can also occur spontaneously, with no known exposure to antiviral medications. If a hospitalized patient treated with oseltamivir manifests progressive lower respiratory symptoms, resistant virus should be considered. However, clinicians should note that failure to improve or clinical deterioration during oseltamivir treatment is more likely to be related to the natural history of acute lung injury and inflammatory damage or onset of other complications (renal failure, septic shock, ventilator-associated pneumonia) than to emergence of oseltamivir resistance. Severely immunosuppressed persons (e.g. hematopoietic stem cell transplant recipients) are at highest risk for emergence of oseltamivir-resistant influenza virus infection during or following oseltamivir treatment. Molecular assays can detect genetic changes in influenza viruses associated with oseltamivir resistance. The CDC Influenza Division is available for consultation as needed.

INFECTION CONTROL

What are the current CDC isolation precautions for H1N1, and when can isolation be discontinued?
Precautions for H1N1 are the same as isolation precautions for seasonal influenza. During the care of any patient, all healthcare personnel in every healthcare setting should adhere to standard precautions, which are the foundation for preventing transmission of infectious agents in all healthcare settings.

Droplet precautions should also be implemented for patients with suspected or confirmed influenza for 7 days after illness onset or until 24 hours after the resolution of fever and respiratory symptoms, whichever is longer, while a patient is in a healthcare facility. In some cases, facilities may choose to apply droplet precautions for longer periods based on clinical judgment, such as in the case of young children or severely immunocompromised patients, who may shed influenza virus for longer periods of time.

In this guidance implementation of precautions is based upon the likelihood of illness and duration of symptoms, and not on the results of diagnostic testing. Our guidelines do not address the use of influenza diagnostic tests in guiding the implementation of infection control precautions.

See Prevention Strategies for Seasonal Influenza in Healthcare Settings for more information.

Given 7-10 day shedding post influenza infection, when is it safe for healthcare workers to return to work? 24 hours after cessation of fever? After 3 days of Tamiflu treatment? Or does it need to be longer, and if yes, what criteria do you advise?
Healthcare personnel (HCP) who develop fever and respiratory symptoms should be excluded from work until at least 24 hours after they no longer have a fever (without the use of fever-reducing medicines such as acetaminophen). Those with ongoing respiratory symptoms should be considered for evaluation by occupational health to determine appropriateness of contact with patients.

If returning to a Protective Environment [3.8 MB, 225 pages], to care for patients such as hematopoietic stem cell transplant patients, HCP should be considered for temporary reassignment or exclusion from work for 7 days from symptom onset or until the resolution of symptoms, whichever is longer. Patients in these environments are severely immunocompromised, and infection with influenza virus can lead to severe disease. Furthermore, once infected, these patients can have prolonged viral shedding despite antiviral treatment and expose other patients to influenza virus infection. Prolonged shedding also increases the chance of developing and spreading antiviral-resistant influenza strains; clusters of influenza antiviral resistance cases have been found among severely immunocompromised persons exposed to a common source or healthcare setting.

See Prevention Strategies for Seasonal Influenza in Healthcare Settings for more information.

I work with a large dialysis provider, would like to know what is the recommendation regarding masks for our group of HCW and patients. We vaccinate both HCW and patients, for those that are not vaccinated should we require mask while in our dialysis center?
The circumstances under which CDC recommends the use of face masks for patients and health-care personnel for control of influenza are outlined in the following guideline: http://www.cdc.gov/flu/professionals/infectioncontrol/healthcaresettings.htm.

For additional comments regarding clinical aspects and management of severe influenza and of patients with H1N1 specifically, please see: 
Uyeki TM. N Engl J Med. Preventing and controlling influenza with available interventions. 2014 Feb 27;370(9):789-91. http://www.nejm.org/doi/full/10.1056/NEJMp1400034

CDC. MMWR Morb Mortal Wkly Rep. Influenza-associated intensive-care unit admissions and deaths – California, September 29, 2013 – January 18, 2014. 2014 Feb 21;63(7):143-7. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6307a2.htm

Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza. N Engl J Med. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. 2010 May 6;362(18):1708-19. http://www.nejm.org/doi/full/10.1056/NEJMra1000449

VACCINATION

Is there any need for re-vaccination or a booster flu vaccine?
Apart from a two-dose recommendation for some children up to eight years of age, CDC does not recommend revaccination or a second dose of vaccine.

Why are there so many flu cases among people who received flu vaccine?
Every season CDC receives reports of some people who were vaccinated against the flu becoming ill and testing positive for the flu. One reason why a person might get the flu even after they have been vaccinated is that a person may be exposed to an influenza virus shortly before getting vaccinated or during the two-week period that it takes the body to gain protection after getting vaccinated. This exposure may result in the person becoming ill with flu before the vaccine begins to protect them.

Unfortunately, some people can also get influenza despite getting vaccinated. Protection provided by influenza vaccination can vary widely, based in part on health and age factors of the person getting vaccinated. In general, the flu vaccine works best among young healthy adults and older children. Some older people and people with certain chronic illnesses may develop less immunity after vaccination. However, even among people who tend to respond less well to vaccination, the flu vaccine can still help prevent influenza. Vaccination is particularly important for people at high risk of serious flu-related complications and for close contacts of high-risk people. For more information about the effectiveness of the flu vaccine, see How Well Does the Seasonal Flu Vaccine Work?

During the 2013-2014 season, CDC received several reports of severe flu illness among young and middle-aged adults, many of whom were infected with the 2009 H1N1 virus; hospitalizations and deaths also were reported. More than 60% of the hospitalizations reported to CDC’s influenza surveillance system were in people 18 to 64 years old. More commonly, most flu hospitalizations occur in people 65 and older.

The more severe impact of pH1N1 on adults aged 18-64 years seen this season and during the pandemic is thought to result from at least two factors. First, persons in this age group likely lack the cross-protective immunity to pH1N1 seen in adults 65 years and older, which was likely acquired from past infection with antigenically related viruses. Second, preliminary vaccination coverage estimates for this season indicate that by early November 2013, adults aged 18-64 years had been vaccinated against influenza at a rate substantially lower (33.9%; 95% confidence interval [CI] = 31.9%-35.9%) than those aged 6 months-17 years (41.1%; 95% CI = 38.8%-43.4%) and those 65 years and older (61.8%; 95% CI = 57.9%-65.7%). In previous years, adults aged 18-64 years also have been less likely to receive influenza vaccine, compared with persons in other age groups. Although some persons infected with pH1N1 during the 2009 pandemic might retain some residual immunity, this protection has likely declined over time. Furthermore, seroprevalence studies showed that only a minority (approximately 35% of all ages combined) were seropositive for pH1N1 after the 2009 pandemic, with even smaller percentages (26%) among those aged 25-64 years.

CDC's mid-season vaccine effectiveness estimates were published on February 20, 2014, in a Morbidity and Mortality Weekly Report entitled: "Interim Estimates of 2013-14 Seasonal Influenza Vaccine Effectiveness—United States." At the end of the season, CDC will provide a comprehensive estimate of VE that takes into account all of the data collected during the season. CDC's mid-season VE estimate was 61% for all age groups (95% confidence interval: 52% to 68%) against having to go to the doctor because of flu illness. This VE estimate means that getting a flu vaccine this season reduced the vaccinated population's risk of having to go to the doctor because of the flu by 60% for both children and adults.

Effectiveness against the 2009 H1N1 virus, which is currently the most common flu virus spreading and causing illness in the United States this season, was 62% (95% CI: 53% to 71%) for children and adults. During the study period (Dec 2, 2013 – January 23, 2014), the 2009 H1N1 virus accounted for 98% of flu viruses detected. (Note: There were not enough influenza B or influenza A (H3N2) viruses detected during the study period to make a mid-season estimate of vaccine effectiveness against either of those viruses.)

When should a pregnant woman be vaccinated -- as early as possible, or after 27 weeks?
Influenza vaccine can be given to pregnant women in any trimester; therefore, there is no reason to delay influenza vaccination for pregnant women.

If the first influenza vaccine was administered early after the vaccine became available in August or September, is a second booster dose of vaccine recommended for this season?
In adults, studies have not demonstrated a benefit of receiving more than one dose during an influenza season, even among elderly persons with weakened immune systems. Except for some children, only one dose of flu vaccine is recommended each season.

For additional information regarding antiviral drugs, including specific references, please see: http://www.cdc.gov/flu/professionals/antivirals/index.htm.