Am Fam Physician. 2002;66(5):894-902
The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has issued recommendations on the prevention and control of influenza for the 2002–2003 influenza season. This report updates the 2001 recommendations by the ACIP for the use of influenza vaccine and antiviral agents.
Epidemics of influenza usually occur during the winter months and are responsible for approximately 20,000 deaths per year in the United States. According to the ACIP, rates of infection are highest among children, but rates of serious illness and death are highest among persons 65 years and older and persons of any age who have medical conditions that place them at increased risk for complications from influenza. Influenza vaccination is the primary method for preventing influenza and its complications. The three groups to be targeted for annual vaccination are (1) persons who are at increased risk for influenza-related complications; (2) persons 50 to 64 years of age, because they have an elevated prevalence of chronic medical conditions; and (3) persons who live with or care for persons at high risk.
The 2002 recommendations include new or updated information about the timing of vaccination by risk group, influenza vaccine in children six to 23 months of age, the 2002–2003 trivalent vaccine virus strains (A/Moscow/10/99[H3N2]-like, A/New Caledonia/20/99 [H1N1]-like, and B/Hong Kong/330/2001-like), and availability of certain vaccine doses with reduced thimerosal.
The recommendations appear in the April 12, 2002 recommendations and reports series of Morbidity and Mortality Weekly Report.
Recommendations for Using Influenza Vaccine
TARGET GROUPS
Groups at high risk for complications from influenza include (1) persons 65 years and older; (2) residents of nursing homes or other facilities of any age who have chronic medical conditions; (3) adults and children with chronic pulmonary or cardiovascular disorders; (4) adults and children who have required medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases, renal dysfunction, hemoglobinopathies, or immunosuppression; (5) persons six months to 18 years of age who are receiving long-term aspirin therapy and might be at risk for Reye's syndrome after influenza infection; and (6) women who will be in the second or third trimester of pregnancy during the influenza season.
SPECIFIC POPULATIONS
According to the ACIP, women who will be beyond their first trimester of pregnancy during the influenza season should be vaccinated because of the increased risk for influenza-related complications. Women with medical conditions that increase their risk for complications should be vaccinated before the influenza season regardless of the stage of pregnancy. The vaccine does not affect the safety of mothers who are breastfeeding or their infants.
Persons with human immunodeficiency virus (HIV) infection, including HIV-infected pregnant women, should be vaccinated because influenza can cause serious complications. Influenza vaccination also provides substantial antibody titers against influenza in persons with minimal acquired immunodeficiency syndrome-related symptoms and high CD4+ T-lymphocyte cell counts.
Travelers at high risk for complications who were not vaccinated during the preceding fall or winter should consider receiving the vaccine if they plan to travel to the tropics because influenza can occur year-round there. They should also be vaccinated if they are traveling to the Southern Hemisphere from April through September, the height of activity in that region. Persons traveling with an organized tour group at any time of the year are candidates for vaccination because they might be exposed to persons from areas where the viruses are circulating.
PERSONS WHO SHOULD NOT BE VACCINATED
Inactivated influenza vaccine should not be given to persons known to have anaphylactic hypersensitivity to eggs or other components of the vaccine without consulting a physician first. Persons with acute febrile illness should not be vaccinated until the symptoms have abated. In those with minor illnesses, with or without fever, the vaccine is not contraindicated, particularly in children with mild upper respiratory tract infection or allergic rhinitis.
TIMING OF VACCINATION
The best time to vaccinate is during October and November, but with distribution delays this is not always possible. The ACIP recommends persons at high risk and health care workers be vaccinated in October and earlier. To avoid missing persons at high risk, vaccination should be offered beginning in September during routine health care visits or hospitalization, if the vaccine is available. Vaccination for children younger than nine years who are receiving the vaccine for the first time should also begin in October because they need a booster dose one month after the initial dose. All other groups should begin vaccination in November, including household members of persons at high risk, healthy persons 50 to 64 years of age, and others who wish to decrease the risk for influenza infection. Vaccination should continue through December and throughout the influenza season as long as vaccine supplies are available, even after influenza activity has been documented in the community.
DOSAGE
Dosage recommendations vary by age group (Table 1). In previously unvaccinated children younger than nine years, two doses administered at least one month apart are recommended. If possible, the second dose should be administered before December. In adults, study results have indicated limited or no improvement in antibody response when a second dose is given during the same season.
| Age group† | Dose | Number of doses | Route‡ |
|---|---|---|---|
| Six to 35 months | 0.25 mL | One or two§ | Intramuscular |
| Three to 8 years | 0.50 mL | One or two§ | Intramuscular |
| Nine years and older | 0.50 mL | One | Intramuscular |
SIDE EFFECTS AND ADVERSE REACTIONS
Physicians should remind patients that inactivated influenza vaccine cannot cause influenza, and respiratory disease unrelated to the vaccine can occur after vaccination. Among adults, the most frequent side effect is soreness at the vaccination site. Fever, malaise, myalgia, and other symptoms can occur, and they most often affect persons who have not been exposed to the influenza virus antigens in the vaccine. Immediate allergic reactions (e.g., hives, anaphylaxis) are rare.
INFLUENZA VACCINE SUPPLY
Difficulties with growing and processing the influenza A vaccine strain and other manufacturing problems caused delays in the distribution of the influenza vaccine in 2000 and 2001. Future delivery delays or vaccine shortages remain possible. The ACIP has addressed the situation, including identifying and implementing ways to strengthen the vaccine supply, improving targeted delivery to groups at high risk, and encouraging the administration of vaccine throughout the influenza season each year.
Recommendations for Using Antiviral Agents for Influenza
Antiviral drugs are an adjunct to the vaccine and should not be considered a substitute for vaccination. Amantadine, rimantadine, zanamivir, and oseltamivir are the four licensed antiviral agents available in the United States. Amantadine and rimantadine are chemically related antiviral drugs with activity against influenza A viruses, but not influenza B. Amantadine was first approved for chemoprophylaxis of influenza A infection and was later approved for treatment in adults and children one year and older. Rimantadine is approved for treatment and chemoprophylaxis of infection in adults and prophylaxis in children.
Zanamivir and oseltamivir have activity against influenza A and B viruses. They are approved for treating uncomplicated influenza infections. Zanamivir is approved for use in persons seven years and older and oseltamivir is approved for use in persons one year and older. Oseltamivir is also approved for chemoprophylaxis in persons 13 years and older. Amantadine, rimantadine, and oseltamivir are administered orally. Zanamivir is administered via oral inhalation.
DIAGNOSIS
Appropriate treatment of patients with respiratory illness depends on accurate and timely diagnosis. If influenza is diagnosed early, the inappropriate use of antibiotics can be reduced, and the option of using antiviral therapy is available. Influenza surveillance data provided by state and local health departments and the CDC provide information about influenza viruses in the community. This information and diagnostic testing can aid clinical judgment and guide treatment decisions. Diagnostic tests available include viral culture, serology rapid antigen testing, polymerase chain reaction, and immuno-fluorescence. Commercial rapid diagnostic tests can be used in outpatient settings and give results in 30 minutes, but physicians should have negative tests confirmed with viral culture or other means because the rapid tests have a lower sensitivity.
TREATMENT
When administered within two days of the start of illness in otherwise healthy adults, amantadine and rimantadine can reduce the duration of uncomplicated influenza A illness, and zanamivir and oseltamivir can reduce the duration of uncomplicated influenza A and B illnesses by about one day compared with placebo. None of these antiviral agents has been demonstrated to be effective in preventing serious influenza-related complications (e.g., bacterial or viral pneumonia or exacerbation of chronic diseases). To reduce the emergence of antiviral drug-resistant viruses, amantadine and rimantadine therapy typically should be discontinued after three to five days of treatment or 24 to 48 hours after the signs and symptoms have disappeared. The recommended course of treatment with zanamivir or oseltamivir is five days.
PROPHYLAXIS
Amantadine and rimantadine are about 70 to 90 percent effective in preventing illness from influenza A infection. When used as prophylaxis, these agents can prevent illness while permitting subclinical infection and the development of protective antibodies against circulating influenza viruses. Oseltamivir and zanamivir are similarly effective in preventing febrile, laboratory-confirmed influenza illness, but only oseltamivir has been approved for prophylaxis. When determining the timing and duration for using antiviral medications, factors related to cost, compliance, and potential side effects should be considered. For maximal efficacy, the medication must be taken every day for the duration of influenza activity in the community.
DOSING
Dosing recommendations vary by age group and medical conditions (Table 2). The guidelines include recommendations for persons 65 years and older and persons with impaired renal function, liver disease, and seizure disorders.
| Age groups | |||||
|---|---|---|---|---|---|
| Antiviral agent | One to six years | Seven to nine years | 10 to 12 years | 13 to 64 years | 65 years and older |
| Amantadine* | |||||
| Treatment, influenza A | 5 mg per kg per day up to 150 mg in two divided doses† | 5 mg per kg per day up to 150 mg in two divided doses† | 100 mg twice daily‡ | 100 mg twice daily‡ | 100 mg or less per day |
| Prophylaxis, influenza A | 5 mg per kg per day up to 150 mg in two divided doses† | 5 mg per kg per day up to 150 mg in two divided doses† | 100 mg twice daily‡ | 100 mg twice daily‡ | 100 mg or less per day |
| Rimantadine§ | |||||
| Treatment||, influenza A | NA | NA | NA | 100 mg twice dailyঠ| 100 mg per day |
| Prophylaxis, influenza A | 5 mg per kg per day up to 150 mg in two divided doses† | 5 mg per kg per day up to 150 mg in two divided doses† | 100 mg twice daily‡ | 100 mg twice daily‡ | 100 mg per day# |
| Zanamivir**†† | |||||
| Treatment, influenza A and B | NA | 10 mg twice daily | 10 mg twice daily | 10 mg twice daily | 10 mg twice daily |
| Oseltamivir | |||||
| Treatment‡‡, influenza A and B | Dose varies by child's weight§§ | Dose varies by child's weight§§ | Dose varies by child's weight§§ | 75 mg twice daily | 75 mg twice daily |
| Prophylaxis, influenza A and B | NA | NA | NA | 75 mg per day | 75 mg per day |
Children
The use of amantadine in children younger than one year has not been thoroughly evaluated. For treatment and prophylaxis in children one to nine years of age, the U.S. Food and Drug Administration has approved 4.4 to 8.8 mg per kg per day, not to exceed 150 mg per day. Physicians should consider prescribing only 5 mg per kg per day (not to exceed 150 mg per day) to reduce the risk of toxicity. For children 10 years or older, the approved dosage is 200 mg per day (100 mg twice a day). Children weighing less than 40 kg (88 lb), regardless of age, should receive 5 mg per kg per day.
Rimantadine is approved for treatment and prophylaxis in children one year and older, but it has not been adequately evaluated in children younger than one year. It should be administered in one or two divided doses at a dosage of 5 mg per kg per day (not to exceed 150 mg per day for children one to nine years of age). For children 10 years or older, the recommended dosage is 200 mg per day (100 mg twice a day). Regardless of age, the dosage should be 5 mg per kg per day if the child weighs less than 40 kg.
Zanamivir is approved for treatment of children seven years or older. The recommended dosage is two inhalations (one 5-mg blister per inhalation) twice daily (about 12 hours apart).
Oseltamivir is approved for treatment in patients one year or older and for prophylaxis in patients 13 years and older. Recommended dosages for children vary by the weight of the child: 15 kg (33 lb) or less is 30 mg twice a day; more than 15 to 23 kg (50.6 lb) is 45 mg twice a day; more than 23 to 40 kg is 60 mg twice a day; and more than 40 kg is 75 mg twice a day. For those 13 years or older, the treatment dosage is 75 mg twice a day, and the prophylaxis dosage is 75 mg once a day.
Persons 65 Years and Older
The daily dosage of amantadine should not exceed 100 mg for prophylaxis or treatment because renal function declines with aging.
Among older persons, the incidence and severity of central nervous system side effects are substantially lower in those taking 100 mg per day of rimantadine than in those taking a dosage adjusted for estimated renal clearance. The common prophylaxis dosage is 100 mg per day, and the treatment dosage is 200 mg per day, but it should be dropped to 100 mg per day if the patient experiences side effects.
There is no recommended reduction in dosage for zanamivir and oseltamivir on the basis of age alone.
SIDE EFFECTS AND ADVERSE REACTIONS
When considering the use of influenza antiviral medications, physicians must consider the patient's age, weight, and renal function; the presence of other medical conditions; indications for use; and the potential for interaction with other medications.
Amantadine and rimantadine can cause central nervous system and gastrointestinal side effects in young, healthy adults at equivalent dosages of 200 mg per day. Incidence of central nervous system side effects (e.g., nervousness, anxiety, insomnia, difficulty concentrating, and lightheadedness) is higher in persons taking amantadine than in those taking rimantadine. These side effects are usually mild and stop shortly after discontinuation of the medicine.
Zanamivir is generally not recommended for patients with underlying airway disease because of the risk for serious adverse events, and efficacy has not been demonstrated in this population. Patients with asthma or chronic obstructive pulmonary disease are advised to have a fast-acting inhaled bronchodilator available when taking zanamivir and to stop taking the drug and contact their physician if they develop difficulty breathing.
Nausea and vomiting were reported more frequently among adults receiving oseltamivir for treatment than among persons receiving placebo. The nausea and vomiting may be less severe if it is taken with food.
These four influenza antiviral drugs should be used in pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus because of the unknown effects of these drugs.