| Persons Who Should Not Be Vaccinated with Inactivated Influenza Vaccine
Inactivated influenza vaccine should not be administered to persons known to have anaphylactic hypersensitivity to eggs or to other components of the influenza vaccine without first consulting a physician (see Side Effects and Adverse Reactions). Prophylactic use of antiviral agents is an option for preventing influenza among such persons. However, persons who have a history of anaphylactic hypersensitivity to vaccine components but who are also at high risk for complications from influenza can benefit from vaccine after appropriate allergy evaluation and desensitization. Information regarding vaccine components is located in package inserts from each manufacturer. Persons with acute febrile illness usually should not be vaccinated until their symptoms have abated. However, minor illnesses with or without fever do not contraindicate use of influenza vaccine, particularly among children with mild upper respiratory tract infection or allergic rhinitis.
Dosage
Dosage recommendations vary according to age group (Table 4). Among previously unvaccinated children aged <9 years, 2 doses administered >1 month apart are recommended for satisfactory antibody responses. If possible, the second dose should be administered before December. If a child aged <9 years receiving vaccine for the first time does not receive a second dose of vaccine within the same season, only 1 dose of vaccine should be administered the following season. Two doses are not required at that time. Among adults, studies have indicated limited or no improvement in antibody response when a second dose is administered during the same season. Even when the current influenza vaccine contains one or more antigens administered in previous years, annual vaccination with the current vaccine is necessary because immunity declines during the year after vaccination. Vaccine prepared for a previous influenza season should not be administered to provide protection for the current season.
Route
The intramuscular route is recommended for influenza vaccine. Adults and older children should be vaccinated in the deltoid muscle. A needle length >1 inch can be considered for these age groups because needles <1 inch might be of insufficient length to penetrate muscle tissue in certain adults and older children.
Infants and young children should be vaccinated in the anterolateral aspect of the thigh. ACIP recommends a needle length of 7/8–1 inch for children aged <12 months for intramuscular vaccination into the anterolateral thigh. When injecting into the deltoid muscle among children with adequate deltoid muscle mass, a needle length of 7/8–1.25 inches is recommended.
Side Effects and Adverse Reactions
When educating patients regarding potential side effects, clinicians should emphasize that 1) inactivated influenza vaccine contains noninfectious killed viruses and cannot cause influenza; and 2) coincidental respiratory disease unrelated to influenza vaccination can occur after vaccination.
Local Reactions
In placebo-controlled studies among adults, the most frequent side effect of vaccination is soreness at the vaccination site (affecting 10%–64% of patients) that lasts <2 days. These local reactions typically are mild and rarely interfere with the person's ability to conduct usual daily activities. One blinded, randomized, cross-over study among 1,952 adults and children with asthma, demonstrated that only body aches were reported more frequently after inactivated influenza vaccine (25.1%) than placebo-injection (20.8%). One study reported 20%–28% of children with asthma aged 9 months–18 years with local pain and swelling and another study reported 23% of children aged 6 months–4 years with chronic heart or lung disease had local reactions. A different study reported no difference in local reactions among 53 children aged 6 months–6 years with high-risk medical conditions or among 305 healthy children aged 3–12 years in a placebo-controlled trial of inactivated influenza vaccine. In a study of 12 children aged 5–32 months, no substantial local or systemic reactions were noted.
Systemic Reactions
Fever, malaise, myalgia, and other systemic symptoms can occur after vaccination with inactivated vaccine and most often affect persons who have had no prior exposure to the influenza virus antigens in the vaccine (e.g., young children). These reactions begin 6–12 hours after vaccination and can persist for 1–2 days. Recent placebo-controlled trials demonstrate that among older persons and healthy young adults, administration of split-virus influenza vaccine is not associated with higher rates of systemic symptoms (e.g., fever, malaise, myalgia, and headache) when compared with placebo injections.
Less information from published studies is available for children, compared with adults. However, in a randomized cross-over study among both children and adults with asthma, no increase in asthma exacerbations was reported for either age group. An analysis of 215,600 children aged <18 years and 8,476 children aged 6–23 months enrolled in one of five health maintenance organizations reported no increase in biologically plausible medically attended events during the 2 weeks after inactivated influenza vaccination, compared with control periods 3–4 weeks before and after vaccination. In a study of 791 healthy children, postvaccination fever was noted among 11.5% of children aged 1–5 years, 4.6% among children aged 6–10 years, and 5.1% among children aged 11–15 years. Among children with high-risk medical conditions, one study of 52 children aged 6 months–4 years reported fever among 27% and irritability and insomnia among 25%; and a study among 33 children aged 6–18 months reported that one child had irritability and one had a fever and seizure after vaccination. No placebo comparison was made in these studies. However, in pediatric trials of A/New Jersey/76 swine influenza vaccine, no difference was reported between placebo and split-virus vaccine groups in febrile reactions after injection, although the vaccine was associated with mild local tenderness or erythema.
Limited data regarding potential adverse events after influenza vaccination are available from the Vaccine Adverse Event Reporting System (VAERS). During January 1, 1991–January 23, 2003, VAERS received 1,072 reports of adverse events among children aged <18 years, including 174 reports of adverse events among children aged 6–23 months. The number of influenza vaccine doses received by children during this time period is unknown. The most frequently reported events among children were fever, injection-site reactions, and rash (unpublished data, CDC, 2003). Because of the limitations of spontaneous reporting systems, determining causality for specific types of adverse events, with the exception of injection-site reactions, is usually not possible by using VAERS data alone.
Health-care professionals should promptly report all clinically significant adverse events after influenza vaccination of children to VAERS, even if the health-care professional is not certain that the vaccine caused the event. The Institute of Medicine has specifically recommended reporting of potential neurologic complications (e.g., demyelinating disorders such as Guillain-Barré [GBS] syndrome), although no evidence exists of a causal relationship between influenza vaccine and neurologic disorders in children.
Immediate –- presumably allergic –- reactions (e.g., hives, angioedema, allergic asthma, and systemic anaphylaxis) rarely occur after influenza vaccination. These reactions probably result from hypersensitivity to certain vaccine components; the majority of reactions probably are caused by residual egg protein. Although current influenza vaccines contain only a limited quantity of egg protein, this protein can induce immediate hypersensitivity reactions among persons who have severe egg allergy. Persons who have had hives or swelling of the lips or tongue, or who have experienced acute respiratory distress or collapse after eating eggs should consult a physician for appropriate evaluation to help determine if vaccine should be administered. Persons who have documented immunoglobulin E (IgE)-mediated hypersensitivity to eggs, including those who have had occupational asthma or other allergic responses to egg protein, might also be at increased risk for allergic reactions to influenza vaccine, and consultation with a physician should be considered. Protocols have been published for safely administering influenza vaccine to persons with egg allergies.
Hypersensitivity reactions to any vaccine component can occur. Although exposure to vaccines containing thimerosal can lead to induction of hypersensitivity, the majority of patients do not have reactions to thimerosal when it is administered as a component of vaccines, even when patch or intradermal tests for thimerosal indicate hypersensitivity. When reported, hypersensitivity to thimerosal usually has consisted of local, delayed hypersensitivity reactions.
Guillain-Barré Syndrome
The 1976 swine influenza vaccine was associated with an increased frequency of GBS. Among persons who received the swine influenza vaccine in 1976, the rate of GBS was <10 cases/1 million persons vaccinated. The risk for influenza vaccine-associated GBS is higher among persons aged >25 years than persons <25 years. Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. Obtaining strong epidemiologic evidence for a possible limited increase in risk is difficult for such a rare condition as GBS, which has an annual incidence of 10–20 cases/1 million adults. More definitive data probably will require using other methodologies (e.g., laboratory studies of the pathophysiology of GBS).
During three of four influenza seasons studied during 1977–1991, the overall relative risk estimates for GBS after influenza vaccination were slightly elevated but were not statistically significant in any of these studies. However, in a study of the 1992–93 and 1993–94 seasons, the overall relative risk for GBS was 1.7 (95% CI = 1.0–2.8; p = 0.04) during the 6 weeks after vaccination, representing approximately 1 additional case of GBS/1 million persons vaccinated. The combined number of GBS cases peaked 2 weeks after vaccination. Thus, investigations to date indicate no substantial increase in GBS associated with influenza vaccines (other than the swine influenza vaccine in 1976), and that, if influenza vaccine does pose a risk, it is probably slightly more than one additional case/1 million persons vaccinated. Cases of GBS after influenza infection have been reported, but no epidemiologic studies have documented such an association. Substantial evidence exists that multiple infectious illnesses, most notably Campylobacter jejuni, as well as upper respiratory tract infections are associated with GBS.
Even if GBS were a true side effect of vaccination in the years after 1976, the estimated risk for GBS of approximately 1 additional case/1 million persons vaccinated is substantially less than the risk for severe influenza, which can be prevented by vaccination among all age groups, especially persons aged >65 years and those who have medical indications for influenza vaccination (Table 1) (see Hospitalizations and Deaths from Influenza). The potential benefits of influenza vaccination in preventing serious illness, hospitalization, and death substantially outweigh the possible risks for experiencing vaccine-associated GBS. The average case fatality ratio for GBS is 6% and increases with age. No evidence indicates that the case fatality ratio for GBS differs among vaccinated persons and those not vaccinated.
The incidence of GBS among the general population is low, but persons with a history of GBS have a substantially greater likelihood of subsequently experiencing GBS than persons without such a history. Thus, the likelihood of coincidentally experiencing GBS after influenza vaccination is expected to be greater among persons with a history of GBS than among persons with no history of this syndrome. Whether influenza vaccination specifically might increase the risk for recurrence of GBS is unknown; therefore, avoiding vaccinating persons who are not at high risk for severe influenza complications and who are known to have experienced GBS within 6 weeks after a previous influenza vaccination is prudent. As an alternative, physicians might consider using influenza antiviral chemoprophylaxis for these persons. Although data are limited, for the majority of persons who have a history of GBS and who are at high risk for severe complications from influenza, the established benefits of influenza vaccination justify yearly vaccination.
|
