Influenza

Updated April 20, 2022

Contents

ACIP Recs | Disease | Vaccine | References | VIS live VIS inactivated 
Advisory Committee on Immunization Practices (ACIP) Recommendations

All Age Groups
  • All persons without contraindications who are at least 6 months of age 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 [1].
  • Live attenuated influenza vaccine (abbreviation: LAIV; trade name: FluMist®) is also an option for non-pregnant persons between 2 and 49 years of age [1].
  • 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 [2].
Infants and Children
  • Children less 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 [1].
For More Information

Important Information for Obstetric Providers

  • Inactivated influenza vaccine (IIV) is routinely recommended during pregnancy.
  • Live attenuated influenza vaccine (LAIV) is contraindicated during pregnancy.

Disease

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 [2].

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 [2,3].

Pregnant women, young children, elderly adults, and persons with pre-existing medical conditions are at increased risk of complications and hospitalizations from influenza [4-6]. 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 [7].

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 [8]. Studies have also estimated an average of approximately 130,000 annual influenza-associated hospitalizations in the United States [5,9].Vaccine

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 starting in the 2018-2019 season it became an option again for non-pregnant persons 2-49 years of age for whom it is otherwise appropriate [10]. LAIV is administered intranasally using a single dose sprayer containing 0.2 mL, with about half (0.1 mL) sprayed in each nostril [1,2,10].

Although the exact strains differ year to year, 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), while quadrivalent vaccines also contain a second B strain [1,2]. The 2020-2021 influenza vaccine viral composition for the U.S. will be: an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus, an A/Hong Kong/2671/2019 (H3N2)-like virus, and a B/Washington/02/2019 (Victoria lineage)-like virus; and that the quadrivalent vaccines also contain a B/Phuket/3073/2013-like (Yamagata lineage) virus [1].

IIVs recommended by the ACIP for use in the United States are detailed in the table below.

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 [2]. Effectiveness has been shown to decline significantly over the first six months post-vaccination, albeit at different rates depending on the vaccine [15-17]. 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 [18].

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 [19-25]. 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 [26], with even higher rates among recipients of the 2009 pandemic H1N1 vaccine [27].

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 [28,29]. 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 [30]. LAIV also cannot cause influenza as it is made from weakened flu virus [31].

Contraindications and Precautions: An important contraindication for IIV and LAIV 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 (exceptions being the recombinant vaccine Flublok® and the cell culture-based Flucelvax Quadrivalent®, which are egg-free) [1]. 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 studies have indicated that egg allergic patients can safely receive influenza vaccines [11,12]. The ACIP recommends that those with a history of egg allergy who have only ever experienced urticaria/hives after egg exposure receive any licensed, recommended influenza vaccine that is otherwise appropriate; whereas those reporting previous reactions to egg involving other symptoms (e.g., angioedema/swelling, respiratory distress, lightheadedness, or recurrent emesis/vomiting) or requiring epinephrine or another emergency medical intervention may also receive any licensed, recommended influenza vaccine that is otherwise appropriate, but if the vaccine contains egg (e.g., is not either the recombinant vaccine Flublok® or the cell culture-based Flucelvax Quadrivalent®), then it should be administered in an inpatient or outpatient medical setting and supervised by a health care provider who is able to recognize and manage severe allergic reactions [1]. The American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American Academy of Pediatrics (AAP) do not recommend any additional special precaution because there does not appear to be any increased risk of severe allergic reactions to these vaccines in persons with egg allergy [13,14].

Other contraindications for LAIV include: pregnancy; children and adolescents receiving concomitant aspirin- or salicylate-containing medications; children 2-4 years old who have received a diagnosis of asthma or have had an asthma or wheezing episode within the last 12 months; immunocompromised persons; those who are close contacts or caregivers of severely immunosuppressed persons requiring a protected environment; persons with cranial CSF leaks; persons with cochlear implants; persons receiving influenza antiviral medication (within the previous 48 hours for oseltamivir and zanamivir, previous 5 days for peramivir, and previous 17 days for baloxavir) [1].

Precautions to IIV and LAIV 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. Other precautions to LAIV include children under 5 years old with asthma, as well as persons with any underlying medical condition other than those already contraindicated which might predispose to complications after infection with wild-type influenza virus [1].

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 [1,2,10,32,33].

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 [4]. 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 [34].

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% [35]. In several other studies, IIV was shown to reduce the risk of low birthweight and premature birth 36,37. Some studies have found that pregnant women who received influenza vaccine had a lower likelihood of stillbirth than those who did not [38-40], although the evidence for this is inconsistent and has methodological limitations [40-42].

A large body of evidence demonstrates the safety of IIV for both pregnant women and their unborn children [43-51]. Concomitant administration of Tdap and influenza vaccines during pregnancy is not associated with a higher risk of adverse outcomes compared to sequential vaccination [52].

In a 2017 publication, Donahue et al. 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 [53]. 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 [53]. However, at the February 2019 ACIP meeting, Donahue presented results from a subsequent case-control study, matched on three age groups and with a population three times the size of the previous study, which revealed no significant association between influenza vaccine receipt and SAb, regardless of prior season vaccination status [54]. One recent randomized trial recruiting women at 17-34 weeks gestation [55], fourteen observational studies [54, 56-68], two systematic reviews [47, 69], and one meta-analysis [38] have assessed a potential association between influenza vaccine and SAb or a related outcome, and none have found an association. See the Do Vaccines Cause Spontaneous Abortion? summary for more details.

Talking Points

Step 1: Establish empathy and credibility
As your doctor, I know that you want to make the best choices about vaccines for you and your family. I also know there is a lot of information out there, and it is difficult to figure out who to trust. Would it be okay if I share with you what I have learned from my experience, and what I share with my patients, my family and my friends about influenza, or the flu for short?
Step 2: Briefly address specific concerns, if any
Flu vaccine actually doesn’t cause the flu. Although some people get some soreness or are a little achy after a flu vaccine, that’s just a sign that your immune system is responding to the vaccine.Even though the flu vaccine doesn’t work 100% of the time at preventing the flu, that doesn’t mean it doesn’t help – it’s still the best way to protect yourself from getting the flu.
Step 3: Pivot to disease risk
Most people don’t realize what a severe illness influenza can be – getting the flu is pretty miserable.Influenza is a virus that is spread by droplets in the air – such as through sneezing and coughing.The flu can cause a sore throat, fever, headache, and cough. It can also cause more severe illness, such as pneumonia and sinus infections. More than 20,000 people die from the flu in the US every year.Pregnant women and infants are at high risk of developing serious complications from the flu and dying from the flu.
Step 4: Convey vaccine effectiveness
The good news about the flu is that there are vaccines. Flu vaccines are developed every year, to match the seasonal strain. You should receive a flu vaccine every year as soon as it is available to protect yourself. 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. Getting the flu vaccine also helps to protect those around you who are most vulnerable to serious influenza illness, such as young children, pregnant women, and the elderly.
Step 5: Give a strong and personalized recommendation
You and I have the same goal: to keep you and your family healthy. You have the power to protect yourself and your family from the flu through vaccination.I strongly recommend flu vaccine to my patients, my family, and my friends.



References

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