ACIP Guidelines for Use of Antiviral Agents for Influenza

 

Most cases of influenza resolve spontaneously, with only a few days of physical distress and loss of productivity as the most significant consequences of illness. However, complications of influenza such as pneumonia and otitis media are common, and the current recommendations focus attention on patients at the highest risk for these complications. Such patients include children younger than 5 years (and, especially, < 2 years), adults 65 years or older, persons with severe chronic illness or immunosuppression, pregnant women, persons with morbid obesity, residents of chronic care facilities, and American Indians/Alaskan Natives.

The Advisory Committee on Immunization Practices provides guidelines for the treatment of these high-risk groups, along with normal-risk individuals, in its current recommendations. It also offers a review of the epidemiology, symptoms, and diagnosis of influenza

Study Highlights

• The main method of transmission of influenza is most likely through person-to-person transmission of large-particle respiratory droplets, which generally travel less than 6 feet in a cough or sneeze.


• Uncomplicated influenza illness usually lasts 3 to 7 days, although cough and malaise may persist for more than 2 weeks.


• Children younger than 5 years with influenza are more likely to demonstrate nonspecific symptoms, such as poor oral intake and irritability, vs older children.


• Influenza is difficult to diagnose on clinical grounds alone. Rapid influenza diagnostic tests offer a high specificity but a low sensitivity. Therefore, a positive rapid test result is usually a reliable indicator of infection with influenza, particularly when influenza activity is high in the community.


• Patients in the high-risk categories described in the Clinical Context section should be treated with antiviral medications. If possible, treatment should be initiated within the first 48 hours of illness.


• Antiviral treatment should also be offered immediately to hospitalized patients as well as to individuals with suspected influenza and severe, complicated, or progressive illness.


• Patients at normal risk for complications may be offered antiviral treatment for known or suspected influenza, provided that treatment is initiated within 48 hours. Antiviral therapy has been demonstrated to reduce influenza symptom duration by approximately 1 day among normal-risk adults.


• Oseltamivir and zanamivir are the preferred antiviral agents for influenza, based on evidence that more than 99% of circulating influenza strains are sensitive to these medications. Amantadine and rimantadine should not be used because of a lack of efficacy against influenza B and high levels of treatment resistance among strains of influenza A.


• Oseltamivir may be used for the treatment of children younger than 1 year.


• Oseltamivir and zanamivir may be used as postexposure chemoprophylaxis for unvaccinated household contacts of patients with influenza. Chemoprophylaxis should only be initiated within 48 hours of the most recent exposure.


• Annual influenza vaccination remains the most effective means to prevent influenza infection and its complications.

Clinical Implications

• The clinical diagnosis of influenza is difficult, and rapid influenza diagnostic tests offer high specificity but low sensitivity. Uncomplicated influenza illness usually lasts 3 to 7 days, although cough and malaise may persist for more than 2 weeks.


• Patients at high risk for complications of influenza should receive treatment with oseltamivir or zanamivir within 48 hours of symptom onset. Treatment with these antivirals is more elective among normal-risk adults, and neither amantadine nor rimantadine should be used to treat influenza.

January 28, 2011 — The US Centers for Disease Control and Prevention Advisory Committee on Immunization Practices has issued updated guidelines regarding the use of antiviral agents for the treatment and chemoprophylaxis of influenza, according to a report in the January 21 issue of the Morbidity and Mortality Weekly Report. The new recommendations, which include a summary of the effectiveness and safety of antiviral treatment medications, update those issued by the committee in 2008.

"Antiviral medications are effective for the prevention of influenza, and, when used for treatment, can reduce the duration and severity of illness," write Anthony E. Fiore, MD, from the Influenza Division, National Center for Immunization and Respiratory Diseases, and colleagues.

"However, the emergence of resistance to one or more of the four licensed antiviral agents (oseltamivir, zanamivir, amantadine, and rimantadine) among some circulating influenza virus strains during the past 5 years has complicated antiviral treatment and chemoprophylaxis recommendations. The selection of antiviral medications should be considered in the context of any available information about surveillance data on influenza antiviral resistance patterns among circulating influenza viruses, local, state, and national influenza surveillance information on influenza virus type or influenza A virus subtype, the characteristics of the person who is ill, and results of influenza testing if testing is done."

Principal changes or updates from the 2008 guidelines for use of antiviral agents for the prevention and control of influenza include the following:

• Antiviral treatment should be started as soon as possible in patients with confirmed or suspected influenza that is severe, complicated, or progressive, or that necessitates hospitalization. Rapid influenza diagnostic test, immunofluorescence, reverse transcription-polymerase chain reaction, or viral culture can be used to confirm influenza virus infection.


• Antiviral treatment should be started in outpatients with confirmed or suspected influenza who are at greater risk for complications of influenza based on age (<5 years, and especially <2 years, or ≥65 years) or underlying medical conditions. These include chronic pulmonary disease (including asthma); cardiovascular disease (except hypertension alone); renal, hepatic, hematologic (including sickle cell disease), and metabolic disorders (including diabetes mellitus); neurologic and neurodevelopmental conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy, stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury); immunosuppression; pregnancy or being up to 2 weeks postpartum; and morbid obesity. Other high-risk groups are persons 18 years of age or younger treated with long-term aspirin, American Indians/Alaska Natives, and residents of nursing homes and other chronic-care facilities. The guidelines authors note that clinical judgment should be an important component of outpatient treatment decisions.


• Oseltamivir and zanamivir are the recommended antiviral medications because recent viral surveillance and resistance data show that more than 99% of currently circulating influenza virus strains are sensitive to these drugs. The recommended duration of treatment is 5 days, but longer treatment regimens may be needed in severely ill hospitalized patients or in immunosuppressed persons. Choice of antiviral drug, dosage, and duration of therapy should be based on the patient's age, weight, and renal function; presence of other medical conditions; indications for use (ie, chemoprophylaxis or therapy); and potential for interaction with other medications.

Either oseltamivir or zanamivir can be used to treat persons with influenza caused by 2009 H1N1 virus, influenza A (H3N2) virus, or influenza B virus, or when the influenza virus type or influenza A virus subtype is unknown. High levels of resistance to amantadine and rimantadine among circulating influenza A viruses suggests that these drugs should not be used at present. However, the guidelines include information about these drugs in case current recommendations change because adamantane-susceptible strains emerge again:

• For treatment or chemoprophylaxis of influenza among infants younger than 1 year, oseltamivir may be used when indicated.


• Based on clinical judgment, antiviral treatment may also be considered for any outpatient with confirmed or suspected influenza without known risk factors for severe illness, as long as treatment can be started within 48 hours of symptom onset.


• Clinicians should monitor local antiviral resistance surveillance data because antiviral resistance patterns can change over time.

"If an emerging public health threat is identified for which no licensed or approved product exists, the Project BioShield Act of 2004 authorizes the [US Food and Drug Administration] Commissioner to issue an [emergency use authorization (EUA)] so appropriate countermeasures (e.g., distribution of unlicensed antiviral medications) can be taken quickly to protect the safety of the U.S. population," the guidelines authors conclude.

"Specifically, these countermeasures can facilitate the diagnosis, treatment, or prevention of serious or life-threatening diseases, or for conditions caused by chemical, biologic, or radiologic agents for which no adequate, approved, or available alternatives exist. [The Centers for Disease Control and Prevention,] in conjunction with [the National Institutes of Health] provides expert consultation to the [US Food and Drug Administration] Commissioner regarding the appropriateness of EUA requests and supports the distribution of products stored in the Strategic National Stockpile...formulary. EUAs in effect during the 2009 H1N1 pandemic have expired because there is no longer a declared emergency."

Morb Mortal Wkly Rep. 2011;60:1-24.