|Naming Conventions for Influenza Vaccines
- The former abbreviation TIV (trivalent inactivated influenza vaccine, previously used for inactivated influenza vaccines) has been replaced with the new abbreviation IIV (inactivated influenza vaccine). For the 2013–14 season, IIVs as a class will include:
- Egg-based and cell culture-based trivalent inactivated influenza vaccines (IIV3)
- Egg-based quadrivalent inactivated influenza vaccine (IIV4)
- RIV refers to recombinant hemagglutinin influenza vaccine, available as a trivalent formulation (RIV3) for the 2013–14 season.
- LAIV refers to live attenuated influenza vaccine, available as a quadrivalent formulation (LAIV4) for the 2013–14 season.
- LAIV, IIV, and RIV denote vaccine categories; numeric suffix specifies the number of antigens in the vaccine.
- When necessary to refer specifically to cell culture-based vaccine, the prefix "cc" is used (e.g., "ccIIV3").
Primary Changes and Updates in the Recommendations
Routine annual influenza vaccination of all persons aged ≥6 months continues to be recommended. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one product is otherwise appropriate. Updated information and guidance in this document include the following:
- 2013–14 U.S. trivalent influenza vaccines will contain an A/California/7/2009 (H1N1)-like virus, an H3N2 virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011, and a B/Massachusetts/2/2012-like virus. Quadrivalent vaccines will include an additional vaccine virus strain, a B/Brisbane/60/2008-like virus.
- Several new, recently licensed vaccines will be available for the 2013–14 season and are acceptable alternatives to other licensed vaccines indicated for their respective age groups. These vaccines include the following:
- A quadrivalent live attenuated influenza vaccine (LAIV4; FluMist Quadrivalent [MedImmune, Gaithersburg, Maryland]) is expected to replace the trivalent (LAIV3) formulation. FluMist Quadrivalent is indicated for healthy, nonpregnant persons aged 2 through 49 years.
- A quadrivalent inactivated influenza vaccine (IIV4; Fluarix Quadrivalent [GlaxoSmithKline, Research Triangle Park, North Carolina]) will be available, in addition to the previous trivalent formulation. Fluarix Quadrivalent is indicated for persons aged ≥3 years.
- An IIV4 (Fluzone Quadrivalent [Sanofi Pasteur, Swiftwater, Pennsylvania]) will be available, in addition to the previous trivalent formulation. Fluzone Quadrivalent is indicated for persons aged ≥6 months.
- An IIV4 (FluLaval Quadrivalent [ID Biomedical Corporation/GlaxoSmithKline]) will be available, in addition to the previous trivalent formulation. FluLaval Quadrivalent is indicated for persons aged ≥3 years.
- A trivalent cell culture-based inactivated influenza vaccine (ccIIV3; Flucelvax [Novartis Vaccines and Diagnostics, Cambridge, Massachusetts]) is indicated for persons aged ≥18 years.
- A recombinant hemagglutinin (HA) vaccine (RIV3; Flublok [Protein Sciences, Meriden, Connecticut]) is indicated for persons aged 18 through 49 years.
- RIV3, an egg-free vaccine, is now an option for vaccination of persons aged 18 through 49 years with egg allergy of any severity.
- For persons with egg allergy who have no known history of egg exposure but for whom results suggestive of egg allergy have been obtained on previous allergy testing, consultation with a physician with expertise in the management of allergic conditions is recommended before vaccination.
Influenza Vaccine Composition for the 2013–14 Season
All influenza vaccines licensed in the United States will contain HA derived from influenza viruses antigenically identical to those recommended by the U.S. Food and Drug Administration (FDA). This season, for the first time, both trivalent and quadrivalent influenza vaccines will be available in the United States. Trivalent influenza vaccines will contain HA derived from three vaccine virus strains: one A(H1N1), one A(H3N2), and one B vaccine virus strain. Quadrivalent vaccines will contain the same the HA antigens as trivalent vaccines, but will also contain HA from a second B virus strain (one B virus strain from each lineage will be represented) (see "Quadrivalent Influenza Vaccines" in the original guideline document).
TIVs will contain HA derived from the following:
- An A/California/7/2009 (H1N1)-like virus
- An (H3N2) virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011 (A/Texas/50/2012 is recommended to replace the A/Victoria/361/2011-like virus used in the 2012–13 vaccine because egg-adaptation of the A/Victoria/361/2011-like virus resulted in mutations that altered antigenicity)
- A B/Massachusetts/2/2012-like (Yamagata lineage) virus. Quadrivalent influenza vaccines will contain these 3 antigens.
- A B/Brisbane/60/2008–like (Victoria lineage) virus
Recommendations for the Use of Influenza Vaccines, 2013–14 Influenza Season
Groups Recommended for Vaccination
Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. Recommendations pertaining to the use of specific vaccines and populations are summarized below.
Timing of Vaccination
In general, health-care providers should begin offering vaccination soon after vaccine becomes available and, if possible, by October. All children aged 6 months through 8 years who are recommended for 2 doses should receive their first dose as soon as possible after vaccine becomes available; these children should receive the second dose ≥4 weeks later. This practice increases the opportunity for both doses to be administered before or shortly after the onset of influenza activity. To avoid missed opportunities for vaccination, providers should offer vaccination during routine health-care visits or during hospitalizations whenever vaccine is available.
Vaccination efforts should be structured to ensure the vaccination of as many persons as possible before influenza activity in the community begins. In any given year, the optimal time to vaccinate cannot be determined precisely because influenza seasons vary in their timing and duration, and more than 1 outbreak might occur in a single community in a single year. In the United States, localized outbreaks that indicate the start of seasonal influenza activity can occur as early as October. However, in >80% of influenza seasons since 1976, peak influenza activity (which often is close to the midpoint of influenza activity for the season) has not occurred until January or later, and in >60% of seasons, the peak was in February or later.
In recent seasons, initial shipments of influenza vaccine have arrived to some vaccine providers as early as July. Very early availability of vaccine as compared with typical onset and peak of influenza activity raises questions related to the ideal time to begin vaccination. Antibody levels induced by vaccine decline over the months after vaccination. Although a 2008 literature review found no clear evidence of more rapid decline among the elderly, a 2010 study noted significant decline in titers 6 months postvaccination among persons aged ≥65 years (though titers still met European Medicines Agency levels considered adequate for protection). More recently, some investigators have estimated vaccine effectiveness over the course of a season, as a function of time since vaccination.
A case-control study conducted in Navarre, Spain, during the 2011–12 season revealed a decline in vaccine effectiveness from 61% (95% confidence interval [CI] = 5–84) in the first 100 days postvaccination to 42% (95% CI = -39–75) for 100–119 days postvaccination and to -35% (95% CI = -211–41) thereafter. This decline primarily affected persons aged ≥65 years, among whom vaccine effectiveness declined from 85% (95% CI = -8–98) to 24% (95% CI = -224–82) to -208 (95% CI = -1,563–43) over these intervals. Most viruses isolated among those infected which were characterized did not match the vaccine strains. A case-control study conducted in the United Kingdom during the same season estimated an overall vaccine effectiveness against A(H3N2) of 53% (95% CI = 0–78) among those vaccinated <3 months, and 12% (95% CI = -31–41) for those vaccinated 3 months or more. The proportion of persons aged ≥65 years was too small to detect a substantial difference in vaccine effectiveness among this age group. Further evaluation of this effect in larger studies and in different seasons is needed. The Advisory Committee on Immunization Practices (ACIP) will continue to evaluate further data as they become available.
While delaying vaccination until later in the season might permit greater immunity later in the season, such deferral might result in missed opportunities to vaccinate, as well as difficulties in vaccinating a population within a more constrained time period. Community vaccination programs should balance maximizing likelihood of persistence of vaccine-induced protection through the season with avoiding missed opportunities to vaccinate or vaccinating after influenza circulation occurs.
Vaccination efforts should continue throughout the season, because the duration of the influenza season varies and influenza activity might not occur in certain communities until February or March. Providers should offer influenza vaccine routinely, and organized vaccination campaigns should continue throughout the influenza season, including after influenza activity has begun in the community. Vaccine administered in December or later, even if influenza activity has already begun, is likely to be beneficial in the majority of influenza seasons. The majority of adults have antibody protection against influenza virus infection within 2 weeks after vaccination.
Available Vaccine Products and Indications
No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one product is otherwise appropriate. A variety of influenza vaccine products are available (see Table 1 in the original guideline document), including (as of August 2013) six newly approved vaccines (see "New and Recently Approved Influenza Vaccine Products" in the original guideline document). For many vaccine recipients, more than one type or brand of vaccine may be appropriate within indications and ACIP recommendations. Considerations for selection of a given vaccine when several appropriate options are available are discussed below. However, not all products are likely to be uniformly available in any practice setting or locality. For newer vaccines, supplies might be limited during the 2013–14 season; moreover, postmarketing safety and effectiveness data are as yet unavailable, prohibiting a full risk-benefit analysis of newer versus previously available products. Therefore, within these guidelines and approved indications, where more than one type of vaccine is appropriate and available, no preferential recommendation is made for use of any influenza vaccine product over another.
Inactivated Influenza Vaccines
IIVs comprise a large group of products. For the 2013–14 season, most IIVs will be trivalent (IIV3), with some quadrivalent (IIV4) also available. Among IIV3 preparations, ccIIV3 will be available. As a class, IIVs include products which might be administered to all persons aged ≥6 months. However, approved age indications for the various IIV products differ (see Table 1 in the original guideline document). Only age-appropriate products should be administered. Providers should consult package inserts and updated CDC/ACIP guidance for current information. Of particular note, although Afluria (CSL Limited) is FDA-approved for children aged >5 years, CDC and ACIP recommend against use of Afluria in persons aged <9 years because of increased risk for febrile reactions noted in this age group with CSL's 2010 Southern Hemisphere IIV3. If no other age-appropriate, licensed inactivated seasonal influenza vaccine is available for a child aged 5 through 8 years who has a medical condition that increases the child's risk for influenza complications, Afluria can be used; however, providers should discuss with the parents or caregivers the potential benefits and risks of influenza vaccination with Afluria in this age group before administering this vaccine.
All IIV preparations contain the same quantity of HA (15 μg per vaccine virus strain per 0.5 mL dose; 45 μg total), except Fluzone Intradermal and Fluzone High-Dose (Sanofi Pasteur). Fluzone Intradermal is approved for persons aged 18 through 64 years, and contains 9 μg of each HA per vaccine virus strain (27 μg total). Fluzone High-Dose is approved for persons aged ≥65 years and contains 60 μg of each HA per vaccine virus strain (180 μg total). Within specified age indications, ACIP expresses no preference for any given IIV over another.
The one IIV product licensed by the FDA for children aged 6 through 36 months contains 0.25 mL/dose. The 0.25 mL dose may be administered from a prefilled single-dose syringe, single-use vial, or multi-dose vial of this age-appropriate formulation. Children aged 36 months through 18 years, and adults receiving intramuscular (IM) preparations of IIV, should receive a 0.5 mL dose. If a pediatric vaccine dose (0.25 mL) is administered inadvertently to an adult, an additional pediatric dose (0.25 mL) should be administered to provide a full adult dose (0.5 mL). If the error is discovered later (after the patient has left the vaccination setting), an adult dose should be administered as soon as the patient can return. Vaccination with a formulation approved for adult use should be counted as a dose if inadvertently administered to a child.
With the exception of Fluzone Intradermal (Sanofi Pasteur), IIVs should be administered intramuscularly. For adults and older children, the deltoid is the preferred site. Infants and younger children should be vaccinated in the anterolateral thigh. Additional specific guidance regarding site selection and needle length for intramuscular administration are provided in ACIP's General Recommendations on Immunization. Fluzone Intradermal is administered intradermally, preferably over the deltoid muscle, using the included delivery system.
Trivalent versus Quadrivalent IIVs
For the first time, during the 2013–14 influenza season, both trivalent (IIV3) and quadrivalent (IIV4) IIVs will be available. The relative quantity of doses of IIV4 that will be available is not certain; however, it is expected that the supply of IIV4 might be limited. Quadrivalent vaccines are designed to provide broader protection against circulating influenza B viruses in seasons during which the B virus contained in trivalent vaccines is not an optimal match to the predominant circulating B viruses. However, vaccination should not be delayed if only IIV3 is available. No preference is expressed for IIV4 over IIV3.
IIVs and Persons Aged ≥65 Years
For persons aged ≥65 years, either an age-appropriate standard-dose IIV (IIV3 or IIV4) or high-dose IIV3 are acceptable options. High-dose IIV3 (available as Fluzone High-Dose) is approved for persons aged ≥65 years. Immunogenicity data from 3 prelicensure studies among persons aged ≥65 years indicated that, compared with standard dose Fluzone, Fluzone High-Dose elicited higher hemagglutination-inhibition (HAI) titers against all three influenza virus strains included in seasonal influenza vaccines recommended during the study period. Whether the higher postvaccination immune responses observed among Fluzone High-Dose vaccine recipients will result in greater protection against influenza illness is under study. Some solicited injection site and systemic adverse events were more frequent after vaccination with Fluzone High-Dose compared with standard Fluzone, but typically were mild and transient. No preferential recommendation is made for high-dose IIV over standard dose IIV for persons aged ≥65 years.
IIVs and Egg Allergy
With the exception of Flucelvax, IIVs are manufactured via propagation of virus in eggs and therefore might contain residual egg protein. Egg protein content (usually described as ovalbumin content as a surrogate measure) is not disclosed on all package inserts (see Table 1 in the original guideline document); where not listed, this information generally can be obtained by contacting the manufacturer. Flucelvax is manufactured from virus propagated in Madin Darby Canine Kidney (MDCK) cells rather than embryonated eggs; however, before production seed virus is created using reference virus strains supplied by the World Health Organization (WHO), which have been passaged in eggs. Flucelvax can therefore not be considered egg-free. The total egg protein is estimated to be <50 femtograms (5x10-14 grams) total egg protein (of which a fraction is ovalbumin) per 0.5 mL dose of Flucelvax (Novartis, unpublished data, 2013). Flucelvax can be administered to persons with a history of mild egg allergy (specifically, those who have experienced only hives following egg exposure; see "Influenza Vaccination of Persons with Egg Allergy" in the original guideline document) who are aged ≥18 years and have no other contraindications. Because no data are available regarding the use of ccIIV among egg-allergic persons, and there is no established safe threshold for ovalbumin content in vaccines, ccIIV should be administered according to the guidance for other IIVs (see "Influenza Vaccination of Persons with Egg Allergy" in the original guideline document).
Contraindications and Precautions for Use of IIVs
Manufacturer package inserts and updated CDC/ACIP guidance should be consulted for current information on contraindications and precautions for individual vaccine products. In general, IIV is contraindicated for, and should not be administered to, persons known to have anaphylactic hypersensitivity to eggs or to any vaccine components (see Table 2 in the original guideline document). Prophylactic use of antiviral agents is an option for preventing influenza among such persons. Information about vaccine components is located in package inserts from each manufacturer.
Moderate or severe acute illness with or without fever is a general precaution for vaccination. Guillain-Barré syndrome (GBS) within 6 weeks following a previous dose of influenza vaccine is considered a precaution for use of influenza vaccines (see Table 2 in the original guideline document).
Recombinant Influenza Vaccine
One RIV product, Flublok, a trivalent recombinant HA vaccine, is expected to be available for the 2013–14 influenza season. This RIV3 is administered by intramuscular injection, and is indicated for persons aged 18 through 49 years. RIV3 is manufactured without the use of influenza viruses; therefore, similarly to IIVs, no shedding of vaccine virus will occur. No preference is expressed for RIV versus IIV within specified indications.
RIV and Egg Allergy
The currently available RIV, Flublok, is manufactured without the use of eggs, and does not carry a contraindication for egg allergy. Therefore, Flublok can be administered to persons with egg allergy of any severity who are aged 18 through 49 years and do not have other contraindications. Since 2011, ACIP has recommended that persons with a history of mild egg allergy (specifically, those who experience only hives following egg exposure) can receive IIV, with additional safety precautions. For such persons, vaccination should not be delayed if RIV is not available; IIV should be used in these settings, following the recommendations outlined (see "Influenza Vaccination of Persons with Egg Allergy" in the original guideline document).
Contraindications and Precautions for Use of RIV
Flublok is contraindicated in persons who have had a severe allergic reaction to any component of the vaccine. Moderate or severe acute illness with or without fever is a general precaution for vaccination. GBS within 6 weeks following a previous dose of influenza vaccine is considered a precaution for use of influenza vaccines (see Table 2 in the original guideline document). Flublok is not licensed for use in children aged <18 years or adults aged >49 years.
Live Attenuated Influenza Vaccine
One LAIV4 product, FluMist Quadrivalent (MedImmune), is expected to be available during the 2013–14 influenza season. FluMist is indicated for nonpregnant persons aged 2 through 49 years who do not have a medical condition that predisposes them to medical complications from influenza. No preference is indicated for LAIV versus other vaccines appropriate for this group.
LAIV is administered intranasally using the supplied 0.2 mL intranasal sprayer (0.1 mL in each nostril). If the vaccine recipient sneezes immediately after administration, the dose should not be repeated. However, if nasal congestion is present that might impede delivery of the vaccine to the nasopharyngeal mucosa, deferral of administration should be considered until resolution of the illness, or IIV should be administered instead.
LAIV versus IIV
Several randomized studies have evaluated the relative effectiveness of LAIV3 as compared with IIV3. Most studies conducted among adults have noted superior relative efficacy of IIV3. A significantly greater relative efficacy of LAIV3 as compared with IIV3 has been noted in several studies conducted among younger children, including a randomized, open label study among children aged 6 through 71 months, a randomized blinded trial of children aged 6 through 59 months, and a randomized blinded trial of children with asthma aged 6 through 17 years. However, no postmarketing safety data are yet available for the new quadrivalent formulation, LAIV4, which will be available for the first time during the 2013–14 season and is expected to replace LAIV3. Therefore, no preferential recommendation is made for LAIV4 over IIV for any age group at this time. This information will be updated as more data become available. Vaccination should not be delayed if LAIV is not available.
LAIV and Egg Allergy
Because of relative lack of data demonstrating safety of LAIV for persons with egg allergy, egg-allergic persons should receive IIV rather than LAIV (see "Influenza Vaccination of Persons with Egg Allergy" in the original guideline document).
Contraindications and Precautions to the Use of LAIV
LAIV is contraindicated for persons with a history of severe hypersensitivity reaction to any component of the vaccine or to a previous dose of any influenza vaccine, and in children and adolescents receiving concomitant aspirin therapy (see Table 2 in the original guideline document). In addition, LAIV should not be administered to the following groups:
- Children aged <2 years
- Adults aged ≥50 years
- Children aged 2 through 4 years whose parents or caregivers report that a health-care provider has told them during the preceding 12 months that their child had wheezing or asthma or whose medical record indicates a wheezing episode has occurred during the preceding 12 months (see Table 1 in the original guideline document)
- Persons with asthma
- Children and adults who have chronic pulmonary, cardiovascular (except isolated hypertension), renal, hepatic, neurologic/neuromuscular, hematologic, or metabolic disorders
- Children and adults who have immunosuppression (including immunosuppression caused by medications or by human immunodeficiency virus [HIV])
- Pregnant women
Moderate or severe acute illness with or without fever is a general precaution for vaccination. GBS within 6 weeks following a previous dose of influenza vaccine is considered a precaution for use of influenza vaccines.
Persons at Risk for Medical Complications Attributable to Severe Influenza
Vaccination to prevent influenza is particularly important for persons who are at increased risk for severe complications from influenza, or at higher risk for influenza-related outpatient, emergency department (ED), or hospital visits. When vaccine supply is limited, vaccination efforts should focus on delivering vaccination to the following persons (no hierarchy is implied by order of listing):
- All children aged 6 through 59 months
- All persons aged ≥50 years
- Adults and children who have chronic pulmonary (including asthma) or cardiovascular (except isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus)
- Persons who have immunosuppression (including immunosuppression caused by medications or by HIV infection)
- Women who are or will be pregnant during the influenza season
- Children and adolescents (aged 6 months through 18 years) who are receiving long-term aspirin therapy and who might be at risk for experiencing Reye's syndrome after influenza virus infection
- Residents of nursing homes and other long-term care facilities
- American Indians/Alaska Natives
- Persons who are morbidly obese (body mass index [BMI] ≥40)
Persons Who Live with or Care for Persons at High Risk for Influenza-Related Complications
All persons aged ≥6 months should be vaccinated annually. Continued emphasis should be placed on vaccination of persons who live with or care for persons at higher risk for influenza-related complications. When vaccine supply is limited, vaccination efforts should focus on delivering vaccination to persons at higher risk for influenza-related complications listed above, as well as these persons:
- Health-care personnel
- Household contacts (including children) and caregivers of children aged ≤59 months (i.e., aged <5 years) and adults aged ≥50 years, with particular emphasis on vaccinating contacts of children aged <6 months
- Household contacts (including children) and caregivers of persons with medical conditions that put them at high risk for severe complications from influenza
Annual influenza vaccination is recommended for all health-care personnel and persons in training for health-care professions. Personnel in health-care settings who should be vaccinated include physicians, nurses, and other workers in inpatient and outpatient-care settings, medical emergency-response workers (e.g., paramedics and emergency medical technicians), employees of nursing home and long-term care facilities who have contact with patients or residents, and students in these professions who will have contact with patients. ACIP guidance for immunization of health-care personnel has been published previously.
Health-care personnel and persons who are contacts of persons in these groups and who are not contacts of severely immunocompromised persons (those living in a protective environment; see "Close Contacts of Immunocompromised Persons" in the original guideline document) may receive any influenza vaccine that is otherwise indicated. Persons who care for the severely immunocompromised should receive either IIV or RIV3. The rationale for avoiding use of LAIV among health-care personnel or close contacts of severely immunocompromised patients is the theoretical risk that a live attenuated vaccine virus could be transmitted to the severely immunosuppressed person. In addition, to further reduce the theoretical risk of vaccine virus transmission, ACIP/Healthcare Infection Control Practices Advisory Committee (HICPAC) has recommended that health-care personnel who receive LAIV should avoid providing care for severely immunosuppressed patients requiring a protected environment for 7 days after vaccination, and that hospital visitors who have received LAIV should avoid contact with severely immunosuppressed persons (i.e., persons requiring a protected environment) for 7 days after vaccination. However, such visitors should not be restricted from visiting less severely immunosuppressed patients. Healthy nonpregnant persons aged 2 through 49 years, including health-care personnel, who have close contact with persons with lesser degrees of immunosuppression (e.g., persons with chronic immunocompromising conditions such as HIV infection, corticosteroid or chemotherapeutic medication use, or who are cared for in other hospital areas such as neonatal intensive care units) can receive LAIV.
Vaccine Dose Considerations for Children Aged 6 Months through 8 Years
Evidence from several studies indicates that children aged 6 months through 8 years require 2 doses of influenza vaccine (administered a minimum of 4 weeks apart) during their first season of vaccination to optimize immune response. In a study of children aged 5 through 8 years receiving IIV3 for the first time, the proportion of children with protective antibody responses was significantly higher (p<0.001 for influenza A[H1N1], p = 0.01 for influenza A[H3N2], and p<0.001 for influenza B) after 2 doses as compared with a single dose. Several studies have indicated that the time interval between 2 initial doses (from 4 weeks up to 1 year) of the same antigen may not be critical. However, because of the antigenic novelty of the 2009 influenza A(H1N1) pandemic virus, which is anticipated to continue circulating during the 2013–14 influenza season, exposure history to this vaccine virus antigen also must be considered. Children who last received seasonal (trivalent) influenza vaccine before the 2010–11 season but did not receive a vaccine containing 2009 (H1N1) antigen (i.e., either in seasonal vaccine since July 2010 or monovalent 2009 [H1N1] vaccine) will not have received this antigen. These children are recommended to receive 2 doses this season, even if 2 doses of seasonal influenza vaccine were received before the 2010–11 season. This recommendation is illustrated in the approaches outlined below. These recommendations are consistent with those of the American Academy of Pediatrics. Two approaches are recommended, both of which are acceptable.
The first approach (see Figure 1 in the original guideline document), takes into consideration only doses of seasonal influenza vaccine received since July 1, 2010. This approach has the advantage of simplicity, particularly in settings in which it is difficult to ascertain vaccination history before the 2010–11 season. Using this approach, children aged 6 months through 8 years need only 1 dose of vaccine in the 2013–14 influenza season if they received a total of 2 or more doses of seasonal vaccine since July 1, 2010. Children who did not receive a total of 2 or more doses of seasonal vaccine since July 1, 2010, require 2 doses in the 2013–14 season.
In settings where adequate vaccination history from before the 2010–11 season is available, the second approach may be used. By this approach, if a child aged 6 months through 8 years is known to have received at least 2 doses of seasonal influenza vaccine during any prior season, and at least 1 dose of a 2009 (H1N1)-containing vaccine (i.e., 2010–11, 2011–12, or 2012–13 seasonal vaccine or the monovalent 2009 [H1N1] vaccine) then the child needs only 1 dose for the 2013–14 season. Using this approach, children aged 6 months through 8 years need only 1 dose of vaccine in the 2013–14 season if they have received any of the following:
- 2 or more doses of seasonal influenza vaccine since July 1, 2010
- 2 or more doses of seasonal influenza vaccine before July 1, 2010 and 1 or more doses of monovalent 2009 (H1N1) vaccine
- 1 or more doses of seasonal influenza vaccine before July 1, 2010, and 1 or more doses of seasonal influenza vaccine since July 1, 2010.
Children aged 6 months through 8 years for whom one of these conditions is not met require 2 doses in the 2013–14 season.
Influenza Vaccination for Pregnant Women
Pregnant and postpartum women are at higher risk for severe illness and complications from influenza than women who are not pregnant because of changes in the immune system, heart, and lungs during pregnancy. Vaccination during pregnancy has been shown to protect infants from influenza, including infants aged <6 months, for whom no influenza vaccines are currently licensed. The ACIP and American College of Obstetricians and Gynecologists (ACOG) recommends that all women who are pregnant or who might be pregnant in the upcoming influenza season receive IIV because of this increased risk for serious illness and complications from influenza. Influenza vaccination can be administered at any time during pregnancy, before and during the influenza season.
Women who are or will be pregnant during influenza season should receive IIV. LAIV is not recommended for use during pregnancy. Postpartum women can receive either LAIV or IIV. Pregnant and postpartum women do not need to avoid contact with persons recently vaccinated with LAIV.
Influenza Vaccination of Persons with a History of Egg Allergy
Severe allergic and anaphylactic reactions can occur in response to a number of influenza vaccine components, but such reactions are rare. With the exceptions of RIV and ccIIV3, currently available influenza vaccines are prepared by propagation of virus in embryonated eggs. A recent review of published data (including 4,172 patients, 513 of whom were reported to have a history of severe allergic reaction to egg) noted that no occurrences of anaphylaxis were reported, though some milder reactions did occur, suggesting that severe allergic reactions to egg-based influenza vaccines are unlikely. Vaccines containing as much as 0.7 μg/0.5 mL have been tolerated; however, a threshold below which no reactions would be expected is not known. Although ovalbumin content is not required to be disclosed on package inserts for vaccines used in the United States, manufacturers either report maximum albumin content in the package inserts or will provide this information on request. Among IIVs for which ovalbumin content was disclosed during the 2011–12 and 2012–13 seasons, reported maximum amounts were ≤1 μg/0.5 mL dose. Ovalbumin is not directly measured for Flucelvax, but it is estimated by calculation from the initial content in the reference virus strains to contain a maximum of 5x10-8 μg/0.5 mL dose of total egg protein (Novartis, unpublished data, 2013). Flublok is egg-free. It should be noted, however, that neither Flucelvax nor Flublok are licensed for children aged <18 years.
Surveillance for Anaphylaxis Following Influenza Vaccination
Following review of available data, since the 2011–12 influenza season, ACIP has recommended that persons with egg allergy who report only hives after egg exposure should receive IIV, with several additional safety measures; current FDA-approved packaging for influenza vaccines lists only severe hypersensitivity to egg protein as a contraindication to vaccination. Review of Vaccine Adverse Event Reporting System (VAERS) data for the 2011–12 and 2012–13 seasons indicated no disproportionate reporting of allergic reaction or anaphylaxis after influenza vaccination during the first 2 seasons the new recommendation was in place. However, during the 2012–13 influenza season, VAERS received one report containing a documented medical history of anaphylaxis following receipt of a first-ever split dose IIV in a child aged 12 months with atopy but no known prior egg ingestion in the past, who had a previous positive allergy skin prick test to ovalbumin. This child had previously received allergy testing attributed to a strong personal and family history of food allergies and other allergies. For the 2013–14 season, the recommendations which follow include guidance concerning persons who have no history of exposure to egg, but who have documented results potentially suggestive of egg allergy on previously performed allergy testing.
For the 2013–14 influenza season, ACIP recommends the following:
- Persons with a history of egg allergy who have experienced only hives after exposure to egg should receive influenza vaccine. Because relatively few data are available for use of LAIV in this setting, IIV or RIV should be used. RIV is egg-free and may be used for persons aged 18 through 49 years who have no other contraindications. However, IIV (egg- or cell-culture based) also may be used, with the following additional safety measures (see Figure 2 in the original guideline document):
- Vaccine should be administered by a health-care provider who is familiar with the potential manifestations of egg allergy.
- Vaccine recipients should be observed for at least 30 minutes for signs of a reaction after administration of each vaccine dose.
- Other measures, such as dividing and administering the vaccine by a 2-step approach and skin testing with vaccine, are not necessary.
- Persons who report having had reactions to egg involving such symptoms as angioedema, respiratory distress, lightheadedness, or recurrent emesis; or who required epinephrine or another emergency medical intervention, particularly those that occurred immediately or within a short time (minutes to hours) after egg exposure, are more likely to have a serious systemic or anaphylactic reaction upon reexposure to egg proteins. These persons may receive RIV3, if aged 18 through 49 years and there are no other contraindications. If RIV3 is not available or the recipient is not within the indicated age range, such persons should be referred to a physician with expertise in the management of allergic conditions for further risk assessment before receipt of vaccine (see Figure 2 in the original guideline document).
- All vaccines should be administered in settings in which personnel and equipment for rapid recognition and treatment of anaphylaxis are available. ACIP recommends that all vaccination providers should be familiar with the office emergency plan.
- Some persons who report allergy to egg might not be egg-allergic. Those who are able to eat lightly cooked egg (e.g., scrambled egg) without reaction are unlikely to be allergic. Egg-allergic persons might tolerate egg in baked products (e.g., bread or cake). Tolerance to egg-containing foods does not exclude the possibility of egg allergy. Egg allergy can be confirmed by a consistent medical history of adverse reactions to eggs and egg-containing foods, plus skin and/or blood testing for immunoglobulin E antibodies to egg proteins.
- For persons who have no known history of exposure to egg, but who are suspected of being egg-allergic on the basis of previously performed allergy testing, consultation with a physician with expertise in the management of allergic conditions should be obtained before vaccination (see Figure 2 in the original guideline document). Alternatively, RIV3 may be administered if the recipient is aged 18 through 49 years.
- A previous severe allergic reaction to influenza vaccine, regardless of the component suspected to be responsible for the reaction, is a contraindication to future receipt of any influenza vaccine.
Influenza Vaccines and Use of Influenza Antiviral Medications
Administration of IIV to persons receiving influenza antiviral drugs for treatment or chemoprophylaxis is acceptable. The effect on safety and effectiveness of LAIV co-administration with influenza antiviral medications has not been studied. However, because antiviral drugs reduce replication of influenza viruses, LAIV should not be administered until 48 hours after cessation of influenza antiviral therapy. If influenza antiviral medications are administered within 2 weeks after receipt of LAIV, the LAIV dose should be repeated 48 or more hours after the last dose of antiviral medication. Alternatively, persons receiving antiviral drugs within the period 2 days before to 14 days after vaccination with LAIV may be revaccinated another approved vaccine formulation (e.g., IIV or RIV).
Concurrent Administration of Influenza Vaccine with Other Vaccines
Limited data are available on the concurrent administration of influenza vaccines with other live vaccines. Use of LAIV3 concurrently with measles, mumps, rubella (MMR) and varicella vaccine among children aged 12 through 15 months has been studied, and no interference with the immunogenicity to antigens in any of the vaccines was observed. Among adults aged ≥50 years, the safety and immunogenicity of zoster vaccine and IIV3 were similar whether administered simultaneously or sequentially spaced 4 weeks apart.
In the absence of specific data indicating interference, following ACIP's general recommendations for vaccination is prudent. Inactivated vaccines do not interfere with the immune response to other inactivated vaccines or to live vaccines. Inactivated or live vaccines can be administered simultaneously with LAIV. However, after administration of a live vaccine (such as LAIV), at least 4 weeks should pass before another live vaccine is administered.
Sources of Information Regarding Influenza and Surveillance
Updated information regarding influenza surveillance, prevention, detection, and control is available at http://www.cdc.gov/flu . U.S surveillance data are updated weekly during October–May on FluView . In addition, periodic updates regarding influenza are published in the Morbidity and Mortality Weekly Report (MMWR) . Additional information regarding influenza vaccine can be obtained from CDC by calling 1-800-232-4636. State and local health departments should be consulted about availability of influenza vaccine, access to vaccination programs, information related to state or local influenza activity, reporting of influenza outbreaks and influenza-related pediatric deaths, and advice concerning outbreak control.
The National Childhood Vaccine Injury Act of 1986 requires health-care providers to report any adverse event listed by the vaccine manufacturer as a contraindication to further doses of the vaccine, or any adverse event listed in the VAERS Table of Reportable Events Following Vaccination that occurs within the specified time period after vaccination. In addition to mandated reporting, health-care providers are encouraged to report any clinically significant adverse event following vaccination to VAERS. Information on how to report a vaccine adverse event is available at http://vaers.hhs.gov/esub/index . Reports can be filed securely online, by mail, or by fax. A VAERS form can be downloaded from the VAERS Web site or requested by sending an e-mail message to email@example.com, by calling 1-800-822-7967, or by sending a request by facsimile to 1-877-721-0366. Additional information on VAERS or vaccine safety is available at http://vaers.hhs.gov/about/index or by calling 1-800-822-7967.
National Vaccine Injury Compensation Program
The National Vaccine Injury Compensation Program (VICP), established by the National Childhood Vaccine Injury Act of 1986, as amended, provides a mechanism through which compensation can be paid on behalf of a person determined to have been injured or to have died as a result of receiving a vaccine covered by VICP. The Vaccine Injury Table lists the vaccines covered by VICP and the associated injuries and conditions (including death) that may receive a legal presumption of causation. If the injury or condition is not on the Table, or does not occur within the specified time period on the Table, persons must prove that the vaccine caused the injury or condition. Eligibility for compensation is not affected by whether a covered vaccine is used off-label or inconsistently with recommendations.
For a claim to be eligible for compensation under the VICP, it must be filed within 3 years after the first symptom of the vaccine injury. Death claims must be filed within 2 years of the vaccine-related death and not more than 4 years after the start of the first symptom of the vaccine-related injury from which the death occurred. When a new vaccine is covered by VICP or when a new injury/condition is added to the Table, claims can be filed within 2 years from the date the vaccine or injury/condition is added to the Table for injuries or deaths that occurred up to 8 years before the Table change. Persons of all ages who receive a VICP-covered vaccine may be eligible to file a claim. Additional information is available at http://www.hrsa.gov/vaccinecompensation or by calling 1-800-338-2382.