In the United States, influenza viruses circulate seasonally, beginning in October and trailing off in April, with the bulk of infections occurring during the winter months.  Both Influenza A and B viruses can cause an acute respiratory illness. Symptoms of uncomplicated influenza include abrupt-onset fever, headache, and malaise accompanied by respiratory manifestations such as a nonproductive cough and sore throat. Certain populations such as the elderly, young children, pregnant women, and those with chronic medical conditions may be more likely to develop serious complications of influenza such as pneumonia, which can lead to death.  The Centers for Disease Control and Prevention (CDC) estimates that around 9 to 35 million people become infected with influenza in the United States each year.

Vaccination and Prevention

The most important step people can take to avoid influenza infection is vaccination. Annual influenza vaccination is recommended for all persons aged ≥6 months that do not have contraindications. Recently, the Advisory Committee on Immunization Practices (ACIP) published updated recommendations for the 2017-2018 influenza season.

Vaccination Options

There are several different manufacturers of influenza vaccines (CDC Table 1).  With regard to content of the influenza vaccines, two different types are available: trivalent vaccines and quadrivalent vaccines.  Trivalent vaccines offer protection against three different influenza virus strains, while the quadrivalent vaccines offer protection against four different strains. Trivalent and quadrivalent vaccines are available in two different forms, inactivated influenza vaccines (IIV) or recombinant influenza vaccines (RIV). Due to low effectiveness against influenza A (H1N1)-pdm09 observed during the 2013-2014 and 2015-2016 seasons, ACIP does not recommend vaccination with the live attenuated influenza vaccine (LAIV4), which is formulated as a nasal spray.

The 2017-2018 trivalent vaccines contain an A/Michigan/45/2015 (H1N1)-pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus and a B/Brisbane/60/2008-like virus (Victoria lineage). In addition, the quadrivalent vaccines contain a B/Phuket/3073/2013-like virus (Yamagata lineage).

ACIP does not give preference to any licensed, recommended, age-appropriate influenza vaccine product over another. See Table 1 on the CDC’s website for information regarding age-related FDA-approvals.

Vaccine Efficacy

Each year, the CDC conducts surveillance to determine how effective the influenza vaccine is against influenza illness. Over the past several years, it has been observed that vaccines work better against influenza B viruses and influenza A (H1N1) viruses than influenza A (H3N2) viruses. Data collected through the U.S. Influenza Vaccine Effectiveness Network during the 2016-2017 season indicate that influenza vaccination reduced the overall risk for influenza-associated medical visits by 42% (95% CI = 35%–48%). Vaccine effectiveness against the predominant influenza A (H3N2) viruses was 34% (95% CI = 24%–42%) and vaccine effectiveness against influenza B viruses was 56% (95% CI = 47%–64%).

Other benefits demonstrated in influenza vaccination studies include:

• Milder flu illness for those who become infected
• Protects others including those who are more vulnerable such as children and elderly
• Protects pregnant women and babies
• Reduces the risk of flu-related hospitalization especially among children, seniors, and those with chronic medical conditions

Influenza Diagnostics

Due to the often non-specific symptoms it produces, diagnosing influenza infection can be difficult. There are several diagnostic tests available to detect influenza. The gold standard influenza diagnostic test is reverse transcriptase polymerase chain reaction (RT-PCR) testing, which can identify the presence of influenza viral RNA in respiratory specimens. RT-PCR is typically done in batches and sent to specialized laboratories, which can result in a long turn-around time. The three more commonly used diagnostic tests are rapid influenza diagnostic tests (RIDTs), which detect viral antigens by immunoassay, digital immunoassays (DIAs), which are automated immunochromatographic antigen detection tests, and rapid nucleic acid amplification tests (NAATs). A recent meta-analysis by Merckx and colleagues found that DIAs and rapid NAATs had a significantly higher sensitivity for influenza A and B than did traditional RIDTs.

The study revealed pooled sensitivities for DIAs (80.0% for influenza A and 76.8% for influenza B) and rapid NAATs (91.6% for influenza A and 95.4% for influenza B) are much higher than those for RIDTs (54.4% for influenza A and 53.2% for influenza B).

Diagnostic Testing

For most outpatients who reside in an area with influenza activity with signs and symptoms of influenza, the CDC does not recommend diagnostic testing to make antiviral treatment decisions. Hospitalized patients with suspected influenza without lower respiratory tract disease should have specimens tested for influenza. In hospitalized patients with suspected influenza and pneumonia with negative upper respiratory tract specimens, a lower respiratory tract specimen can be tested if a positive result would change clinical management.

Treatment and Chemoprophylaxis

There are three influenza antiviral medications that are approved by the FDA and were recommended for use during the 2016-2017 season. The three agents are oseltamivir (Tamiflu®), which is available as an oral capsule, zanamivir (Relenza®), which is available as an inhalation, and peramivir (Rapivab®), which is available intravenously.  For dosage and duration recommendations, see Table 3 on Antiviral Medications from the CDC. These drugs are all neuraminidase inhibitors and are active against influenza A and B.

ACIP does not recommending testing or treatment in adults ≤65 years of age who present >48 hours after symptom onset and do not have high-risk conditions. Treatment of these patients can be considered to decrease duration of illness if they present within 48 hours of symptom onset.

ACIP recommends treatment regardless of age and time of presentation in individuals who meet any of the following criteria:

• Illness requiring hospitalization
• Progressive, severe, or complicated illness, regardless of previous health or vaccination status
• Residents of nursing homes and other chronic care facilities
• Children aged <2 years
• Adults ≥65 years of age
• Pregnant women and women up to two weeks postpartum
• Persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), metabolic disorders (including diabetes mellitus) or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability [mental retardation], moderate to severe developmental delay, muscular dystrophy, or spinal cord injury)
• Persons with immunosuppression; including that caused by medications or HIV infection
• Persons aged <19 years who are receiving long-term aspirin therapy
• Native Americans and Alaska Natives
• Individuals who are morbidly obese (body mass index [BMI] ≥40)

Postexposure prophylaxis may be considered for unvaccinated persons at high-risk for influenza complications after a household member or other close contact has been diagnosed with laboratory-confirmed influenza. Unvaccinated health-care workers who have occupational exposures may also be considered for postexposure prophylaxis. In addition, preexposure prophylaxis has a very limited role and should only be used in individuals who have a high risk of exposure and are at very high risk for influenza complications, such as those who are severely immunocompromised or residents of a nursing facility during an outbreak, who cannot be protected by other means.

Tracking Influenza Activity

The CDC collaborates with a variety of state and local partners to compile and analyze seasonal influenza activity in the United States. For weekly surveillance reports, click on this link for FluView. For more detailed surveillance reports, click on this link for FluView Interactive.

Written by Deanna Buehrle, PharmD

References:

1. Centers for Disease Control and Prevention. Disease Burden of Influenza. https://www.cdc.gov/flu/about/disease/burden.htm (Accessed on October 6, 2017).
2. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices – United States, 2017-18 Influenza Season. MMWR Recomm Rep. 2017 Aug 25;66(2):1-20.
3. Blanton L, Alabi N, Mustaquim D, et al. Update: Influenza Activity in the United States During the 2016–17 Season and Composition of the 2017–18 Influenza Vaccine. MMWR Morb Mortal Wkly Rep. 2017 Jun 30;66(25):668-676.
4. Merckx J, Wali R, Schiller I, et al. Diagnostic Accuracy of Novel and Traditional Rapid Tests for Influenza Infection Compared With Reverse Transcriptase Polymerase Chain Reaction: A Systematic Review and Meta-analysis. Ann Intern Med. 2017 Sep 19;167(6):394-409.
5. Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm (Accessed October 7, 2017).
6. Fiore AE, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza – Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 21;60(1):1-24.