November-December 2018

Candace Gragnani, MD, MPH, FAAP

Prabhu Gounder, MD, MPH, FACP

Winter is coming and influenza season is upon us. Los Angeles County (LAC) experienced an especially severe flu season in 2017-2018 with the highest levels of influenza activity and the greatest number of influenza-associated deaths (IADs) observed in the last 5 seasons.¹ Health care providers need to be prepared for the possibility of another severe season this winter. This article will review key points about influenza diagnosis, management, and reporting as you prepare to face the upcoming flu season.

Influenza vaccination efforts should continue throughout the flu season. Peak illness in LAC generally occurs between December and February and disease may continue through March or later. See the September-October Rx for Prevention article, “Preventing Influenza in Los Angeles County” for a summary of vaccination recommendations and information on the Health Officer Order for annual influenza vaccination or masking of health care personnel.

Influenza Testing

Knowing the characteristics of the influenza tests used at your institution can inform proper ordering of tests and interpretation of results in your setting. Remember that influenza virus testing is not required to make a clinical diagnosis in the outpatient setting, especially when local flu prevalence is high.²

Who to Test

• The Centers for Disease Control and Prevention (CDC) recommends testing all hospitalized patients with suspected influenza infection because prompt diagnosis helps minimize nosocomial influenza outbreaks and maximize potential treatment benefits.³
• At the start of influenza season, consider testing patients with suspected influenza infection when it would help determine influenza’s presence in the community and provide valuable information to guide future clinical decisions.⁴
• Consider testing patients with signs or symptoms of influenza if test results would change infection control strategies, such as if they are a part of a respiratory disease outbreak in an institutional facility or closed setting.⁵
• Consider testing outpatients with symptoms of influenza when testing will inform management decisions, such as: (1) the need for antibiotic or antiviral therapy, (2) the need for additional diagnostic testing, (3) decisions regarding the level of care, and (4) advice for ill patients living in households with persons at high risk for complications from influenza.³

When to Test

• Test as close to symptom onset as possible, ideally within 3-4 days. This maximizes your chance of viral detection and minimizes false negative and false positive test results.³

How to Test

• There are several FDA-cleared influenza diagnostic tests that can detect the presence of influenza viral antigen or nucleic acids in respiratory specimens.
• Molecular assays (e.g., rapid molecular assays, Reverse Transcription-Polymerase Chain Reaction [RT-PCR], and other nucleic acid amplification tests) are the most accurate tests for diagnosing influenza because they have a high sensitivity and specificity for detecting influenza virus.² Molecular tests are preferred for hospitalized patients.
• Rapid antigen detection tests (RADTs) may be useful in the outpatient setting as a positive result confirms influenza in a patient with suggestive signs and symptoms. A negative RADT result, however, does not exclude influenza virus infection, especially during times of high flu prevalence in the community.^2,6 If you are using RADTs to dictate a plan of care, a negative RADT result should be confirmed with a molecular assay.⁴
• For more information on influenza testing and result interpretation, see the CDC’s clinician guidance on influenza testing, influenza virus testing methods (including a table for acceptable specimens), and influenza specimen collection.

Influenza Treatment

Antiviral medications can be used to both treat and prevent influenza. Antiviral treatment should begin as early as possible (ideally within 48 hours of symptom onset) and never be delayed while awaiting test results.⁷ Influenza treatment can shorten fever and symptom duration and reduce the risk of influenza-related complications, like pneumonia and respiratory failure.⁷ In hospitalized patients, early antiviral treatment of influenza has been shown to shorten inpatient stays in children and reduce the risk of death in adults.⁷

Who to Treat

• Treat any suspected or confirmed case of influenza in a patient who is hospitalized or has severe, complex, or progressive disease.²
• Treat people with suspected or confirmed influenza who are at high risk for complications; this includes children younger than 2 years of age and adults aged 65 and older. See the CDC’s complete list of people at higher risk.⁷
• Outpatients presenting within 48 hours of symptom onset with suspected or confirmed influenza who are not at high risk for complications may also benefit from treatment.⁷

When to Treat

• Treat influenza patients as soon as possible if they are at high risk for complications or if they have severe disease.⁷
• Antivirals may still provide some clinical benefits to patients with severe, complicated, or progressive illness and patients hospitalized with influenza even when started more than 48 hours after illness onset.*^7,8,9
• Antivirals are most effective for healthy persons when given in the first 48 hours after influenza symptom onset.⁷

* There are no available data on the use of baloxavir for treatment of influenza more than 2 days after illness onset.

How to Treat

• This season, the neuraminidase inhibitors—oral oseltamivir, intravenous peramivir, and inhaled zanamivir—as well as oral baloxavir (a new influenza antiviral drug with a different mechanism of action), are recommended for the treatment of suspected or confirmed influenza. All four have activity against both influenza A and B viruses. See the CDC’s recommended antiviral medication table. Amantadine and rimantadine are not recommended given high levels of resistance among circulating influenza A.⁷
• The recommended antiviral treatment course for outpatients with acute uncomplicated influenza is twice daily oral oseltamivir for 5 days, twice daily inhaled zanamivir for 5 days, a single dose of intravenous peramivir, or a single dose of oral baloxavir.⁷ See the CDC’s antiviral dosing and duration table.
  Of note, oral oseltamivir is the preferred treatment for pregnant women, baloxavir is not recommended during pregnancy or breastfeeding, and inhaled zanamivir is not recommended for use in those with underlying respiratory disease (like COPD and asthma).⁷ 
• There are multiple challenges regarding the treatment of outpatients with severe, progressive, or complicated influenza and patients with severe influenza requiring hospitalization, including lack of clinical trials of current antiviral therapies in the severely ill. See CDC's guidance for treatment considerations.

Influenza Chemoprophylaxis

Although receiving annual influenza vaccinations is the best way to prevent flu, antiviral chemoprophylaxis is an important adjunct to flu prevention. Whereas the CDC does not recommend the routine use of antiviral medications as chemoprophylaxis for influenza exposures, antiviral chemoprophylaxis can be considered to help prevent flu in certain situations.⁷

Who to Chemoprophylax

Antiviral medications can be considered for chemoprophylaxis when you want to prevent influenza in a patient at high risk for complications who:

• Is exposed to influenza during the first 2 weeks after receiving an inactivated influenza vaccine
• Cannot receive an influenza vaccination after an exposure to influenza or
• Might not have responded to the influenza vaccination after exposure to a person with influenza.⁷

When to Chemoprophylax

In general, antiviral chemoprophylaxis is not recommended >48 hours after a patient’s first exposure to a person with influenza.⁷

How to Chemoprophylax

• Only oral oseltamivir and inhaled zanamivir are recommended for influenza chemoprophylaxis.⁷ See the recommended antiviral medication table.
• The recommended antiviral chemoprophylaxis course for influenza is once daily oral oseltamivir or inhaled zanamivir for the duration of potential exposure to a person infected with influenza and an additional 7 days after the last known exposure.⁷  See the antiviral dosing and duration table.

For more information on medication dosing, chemoprophylaxis in institutional settings or hospitals, chemoprophylaxis for health care personnel, treatment in the inpatient setting, timing considerations for concomitant influenza vaccination and antiviral therapy, or additional management considerations, please see the CDC’s influenza antiviral medications webpage.

Influenza Reporting in Los Angeles County

As a clinician on the frontline, it is important to know LAC Department of Public Health (DPH) influenza case reporting requirements.

What to Report

• Any suspected outbreaks in healthcare associated institutions, non-healthcare associated institutions, or congregate settings
• All cases of suspected or confirmed “novel” influenza A infection, including avian flu (H5N1 or H7N9) and swine flu (H3N2v, H1N1v, H1N2v)
• Confirmed influenza-associated death occurring in persons of any age. 

References

1. Los Angeles County Department of Public Health. Influenza Watch: 2017-2018 Season Summary. http://www.publichealth.lacounty.gov/acd/docs/Flu/Season17-18/SeasonSummary.pdf. Accessed October 10, 2018.
2. Overview of influenza testing methods. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/flu/professionals/diagnosis/overview-testing-methods.htm. Updated February 20, 2018. Accessed September 13, 2018.
3. Guide for considering influenza testing when influenza viruses are circulating in the community. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/flu/professionals/diagnosis/consider-influenza-testing.htm. Updated February 20, 2018. Accessed September 13, 2018.
4. Rapid diagnostic testing for influenza: information for clinical laboratory directors. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/flu/professionals/diagnosis/rapidlab.htm. Updated March 6, 2018. Accessed September 13, 2018.
5. Influenza virus testing in investigational outbreaks in institutional or other closed settings. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/flu/professionals/diagnosis/guide-virus-diagnostic-tests.htm. Updated February 20, 2018. Accessed September 13, 2018.
6. Algorithm to assist in the interpretation of influenza testing results and clinical decision-making during periods when influenza viruses are circulating in the community. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/flu/professionals/diagnosis/algorithm-results-circulating.htm. Updated February 20, 2018. Accessed September 24, 2018.
7. Influenza antiviral medications: summary for clinicians. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. Updated November 13, 2018. Accessed November 13, 2018.
8. Yu H, Feng Z, Uyeki TM, et al. Risk factors for severe illness with 2009 pandemic influenza A (H1N1) virus infection in China. Clin Infect Dis. 2011;52(4):457-465. doi:10.1093/cid/ciq144
9. Louie JK, Yang S, Acosta M, et al. Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. Clin Infect Dis. 2012;55(9):1198-1204. doi:10.1093/cid/cis636