Vaccine Preventable Diseases
Advisory Committee on Immunization Practices (ACIP) Recommendations
All Age Groups
• All persons without contraindications who are 6 months of age and older should receive annual vaccination with influenza vaccine.
• Inactivated influenza vaccine (abbreviation: IIV; trade names: see the table on the following pages) is recommended for all age groups and during pregnancy .
• Live attenuated influenza vaccine (abbreviation: LAIV; trade name: FluMist®) is also an option for non-pregnant persons between 2 and 49 years of age .
• Influenza vaccine should be given as soon as it becomes available (usually between August and October in the U.S.) in order to ensure the highest possible level of protection before rates of transmission increase. Peak transmission season is usually between December and March in the United States .
Infants and Children
• Children younger than 9 years of age receiving IIV for the first time ever should receive two doses at least one month apart; otherwise, one dose per year is sufficient .
For More Information
• ACIP recommendations: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html
• Immunization schedules: http://www.cdc.gov/vaccines/schedules/index.html
Influenza is caused by RNA viruses of three types. Type A influenza is the cause of most human illness and has many subtypes based on the variations in the surface antigens (i.e., hemagglutinin (H) and neuraminidase (N)), such as H1N1 or H3N2. Type B influenza also infects humans but generally causes milder illness. Type C only very rarely causes human disease.
The surface antigens on influenza viruses are always evolving, faster than most other viruses that cause human disease. This continuous stream of minor mutations is called antigenic drift and is what makes influenza so adept at evading immunity induced by prior infection or vaccination. In most years, at least some of the circulating influenza strains have drifted compared to prior years, thus even those who were infected or vaccinated in years prior may develop influenza disease again.
Occasionally a major change in one or both surface antigens occurs, known as antigenic shift; the majority of the population is usually susceptible to the new virus. The new strains generated in this manner, such as the 2009 influenza A H1N1, have the potential to cause a worldwide pandemic .
The incubation period for influenza is generally 2 days. The major clinical symptoms typically last a median of 4 days without treatment and include sore throat, fever, headache, myalgia, and nonproductive cough. Pneumonia is the most common complication of influenza. Other complications include Reye syndrome and myocarditis [3, 4].
Pregnant women, young children, elderly adults, and persons with pre-existing medical conditions are at increased risk of complications and hospitalizations from influenza [5-7]. There was an average of 113 annual pediatric deaths from influenza in the United States between 2010 and 2016, and about half of these were in children with no preexisting medical condition .
The CDC estimated an average of 23,607 annual influenza-associated deaths in the United States between 1976 and 2007 among all age groups, although these estimates ranged widely from year to year . Studies have also estimated an average of approximately 130,000 annual influenza-associated hospitalizations in the United States [6, 10].
Two types of vaccines are available to protect against influenza: inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV). LAIV (trade name: FluMist®) was not recommended for use during the 2016-2017 or 2017-2018 flu seasons due to problems with low effectiveness during the previous several seasons, but is again an option for the 2018-2019 season for non-pregnant persons 2-49 years of age for whom it is otherwise appropriate
. LAIV is administered intranasally using a single dose sprayer containing 0.2 mL, with about half (0.1 mL) sprayed in each nostril [1-3].
In the United States, quadrivalent IIV (IIV4) vaccines include Fluarix® Quadrivalent, FluLaval® Quadrivalent, and Fluzone® Quadrivalent; trivalent IIV (IIV3) include Afluria®, Fluvirin®, and Fluzone®. There are two recombinant influenza vaccines, Flublok® (RIV3) and Flublok® Quadrivalent (RIV4). Trivalent vaccines contain one A/H3N2 strain, one A/H1N1 strain, and one B strain from one of the two B lineages (Yamagata and Victoria). The Quadrivalent vaccines contain a second B strain [1,3].
The Food and Drug Administration (FDA) has recommended that the trivalent influenza vaccines used in the United States during the 2018-19 season contain an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017-like (B/Victoria lineage) virus; and that the quadrivalent vaccines also contain a B/Phuket/3073/2013-like (B/Yamagata lineage) virus .
Inactivated Influenza Vaccine (IIV)
|Route of administration: Primarily intramuscular (IM), one intradermal (ID); specified for each vaccine listed below.|
|Vaccine Virus: Inactivated, split or subvirion.
|Trade Name||Dose Available||Age Range Approved|
|Fluzone® Quadrivalent||0.25 mL prefilled syringe or
5.0 mL multi-dose vial (IM)
|≥ 6-35 months of age|
|Fluzone® Quadrivalent||0.5 mL single-dose vial or
prefilled syringe or
5.0 mL multi-dose vial (IM)
|≥ 36 months of age|
|Fluzone® Quadrivalent||5.0 mL multi-dose vial (IM)||≥ 6 months of age|
|Fluarix® Quadrivalent||0.5 mL single-dose prefilled syringe (IM)||≥ 6 months of age|
|FluLaval® Quadrivalent||5.0 mL multi-dose vial (IM)||≥ 6 months of age|
|Flucelvax® Quadrivalent||0.5 mL single-dose prefilled syringe (IM)||≥ 4 years of age|
|Afluria®||0.5 mL single-dose prefilled syringe or
5.0 mL multi-dose vial (IM)
|≥ 5 years of age|
|Afluria® Quadrivalent||0.5 mL prefilled syringe (IM)||> 5 years of age|
|Afluria® Quadrivalent||5.0 mL multi-dose vial (IM)||5 years of age (by needle/syringe)
18-64 years of age (by jet injector)
|Fluvirin®||0.5 mL single-dose prefilled syringe or
5.0 mL multi-dose vial (IM)
|≥ 4 years of age|
|Fluad®||0.5 mL single-dose prefilled syringe (IM)||≥ 4 years of age|
|Fluzone® High-Dose||0.5 mL single-dose prefilled syringe (IM)||≥ 65 years of age|
|Flublok®||0.5 mL single-dose vial (IM)||≥ 18 years of age|
|Flublok® Quadrivalent||0.5 mL single-dose vial (IM)||>18 years of age|
|Flublok® Quadrivalent||0.5 mL single-dose vial (IM)||≥ 18 years of age|
|Fluzone® Intradermal Quadrivalent||0.1 mL single-dose prefilled microinjection system) (ID)||18-64 years of age|
Vaccine Effectiveness: The effectiveness of influenza vaccines varies each year in relation to the match between the vaccine strains and the circulating strain. Effectiveness can also vary by the age and health status of the vaccine recipient . Effectiveness has been shown to decline significantly over the first six months post-vaccination, albeit at different rates depending on the vaccine [16-18]. However, even in years when the vaccine has a lower effectiveness relative to other years, receiving the vaccine still reduces risk of infection, severe illness, hospitalization, and death due to influenza. In addition, high vaccine coverage prevents disease transmission and helps to protect those most vulnerable to serious influenza illness .
Vaccine Safety: Common adverse reactions to IIV include local reactions such as soreness, erythema and induration at the injection site, which are reported at variable rates, but are usually mild and typically last no more than 2 days. Systemic symptoms such as sensation of fever, chills, malaise, and myalgia are also common. These symptoms typically begin within 6–12 hours of vaccination and usually last for only a few hours. Such symptoms are usually mild but have been reported in 4-<30% of children receiving IIV [20-26]. Myalgia within a week of vaccination has been reported among 14-16% of adults receiving unadjuvanted IIV and 31-39% of adults receiving adjuvanted IIV , with even higher rates among recipients of the 2009 pandemic H1N1 vaccine .
Rarely, allergic reactions such as hives, angioedema, allergic asthma, or systemic anaphylaxis occur after vaccination, probably due to hypersensitivity to a vaccine component. See the Do Vaccines Cause Hypersensitivity Reactions? summary for more details.
Influenza vaccination in recent years has been associated with a very small increased risk of GBS in adults, leading to about 1-3 excess cases of GBS per million persons vaccinated. This is much less than the estimated risk after wild-type influenza infection, providing further evidence that the benefits of influenza vaccination greatly outweigh the risks [29,30]. See the Do Vaccines Cause Guillain-Barré Syndrome (GBS)? summary for more details.
IIV cannot cause influenza, as all viruses contained in the vaccine are inactivated and noninfectious . LAIV also cannot cause influenza as it is made from weakened flu virus .
Contraindications and Precautions: An important contraindication is having had a severe allergic reaction (e.g. anaphylaxis) to a vaccine component or previous vaccination. However, this does not include egg allergies, even though most influenza vaccines are grown in embryonated chicken eggs (an exception being the egg-free recombinant influenza vaccine, Flublok®) . This is because the vaccines marketed in the United States have been found to contain extremely small amounts or undetectable amounts of egg protein and recent studies have indicated that egg allergic patients can safely receive influenza vaccines [12, 13]. The ACIP recommends that persons with a severe egg allergy (who have had associated angioedema, respiratory distress, lightheadedness, or recurrent emesis, or who required epinephrine or another emergency medical intervention following egg ingestion) can receive these vaccines, but the vaccine should be administered in an inpatient or outpatient medical setting . However, the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American Academy of Pediatrics (AAP) do not recommend any special precaution because there does not appear to be any increased risk of severe allergic reactions to these vaccines in persons with egg allergy [14,15].
Precautions include moderate to severe acute illness with or without fever, as well as a diagnosis of Guillain-Barré syndrome (GBS) within 6 weeks after a previous dose of influenza vaccine .
Precautions include moderate to severe acute illness with or without fever, as well as a diagnosis of Guillain-Barré Syndrome (GBS) within 6 weeks after a previous dose of influenza vaccine .
The complete current recommendations of the ACIP regarding influenza vaccine delivery can be found at the following website: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html.
Considerations in Pregnancy:
• Inactivated influenza vaccine (IIV) is routinely recommended during pregnancy.
• Live attenuated influenza vaccine (LAIV) is contraindicated during pregnancy .
Pregnant women and young children are at increased risk of complications and hospitalizations from influenza. Infection with influenza during pregnancy has been associated with an increased risk of adverse outcomes to the mother including respiratory hospitalization, pneumonia, adult respiratory distress syndrome, overwhelming sepsis and death . A recent CDC study estimated that 12% of all pregnancy-related deaths during the 2009-2010 pandemic season were attributed to confirmed or possible infection with pandemic influenza .
IIV was shown to reduce non-specific febrile respiratory illness in pregnant women by over one third. Vaccine effectiveness was most pronounced during influenza season. Vaccination in pregnancy is beneficial not just for the mother, but for her unborn child as well. Maternal influenza vaccination was shown in one study to reduce proven influenza illness in infants under 6 months of age by up to 63% . In several other studies, IIV was shown to reduce the risk of low birthweight and premature birth [35, 36]. Some studies have found that pregnant women who received influenza vaccine had a lower likelihood of stillbirth than those who did not [37-39], although the evidence for this is inconsistent and has methodological limitations [39-41].
A large body of evidence demonstrates the safety of IIV for both pregnant women and their unborn children [42-48]. Concomitant administration of Tdap and influenza vaccines during pregnancy is not associated with a higher risk of adverse outcomes compared to sequential vaccination . .
Donahue et al. recently reported results from a case-control study examining the risk of spontaneous abortion (SAb) following receipt of inactivated influenza vaccines containing A/H1N1pdm2009 antigen in the 2010-11 and 2011-12 seasons . The study found an association between influenza vaccine and SAb, particularly among women who had received pandemic H1N1 vaccine in the previous year as well . The findings were most striking in the 2010-2011 season, and were far less pronounced in the 2011-2012 season. The Donahue et al. findings need to be interpreted in the context of other epidemiological data . One recent randomized trial recruiting women at 17-34 weeks gestation , thirteen other observational studies [53-65], two systematic reviews [46, 66], and one meta-analysis  have assessed a potential association between influenza vaccine and SAb or a related outcome, and none have found an association. However, none of these studies examined the effect of multiple dosing. Studies are in progress to assess whether this association is seen in subsequent influenza seasons. See the Do Vaccines Cause Spontaneous Abortion? summary for more details.
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