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Influenza is an infectious viral illness. The name “influenza” 

originated in 15th century Italy, from an epidemic attributed 

to “influence of the stars.” The first documented pandemic, or 

worldwide epidemic, that clearly fits the description of influenza 

was in 1580. At least four pandemics of influenza occurred in 

the 19th century, three in the 20th century, and one thus far 

in the 21st century. The pandemic of “Spanish” influenza in 

1918–1919 caused an estimated 21 million deaths worldwide. 

Wilson Smith, Christopher Andrewes, and Patrick Laidlaw 

isolated influenza A virus in ferrets in 1933, and Thomas Francis 

Jr. isolated influenza B virus in 1936. Also in 1936, Macfarlane 

Burnet discovered that influenza virus could be grown in 

embryonated hens’ eggs. This led to the study of the virus’s 

characteristics and the development and use of inactivated 

vaccines in the late 1930s and 1940s. The protective efficacy 

of these inactivated vaccines was demonstrated in the 1950s. 

The first live, attenuated influenza vaccine was licensed in 2003. 

A non-live, recombinant influenza virus vaccine not requiring 

isolation or growth in hen’s eggs was licensed in 2013.

Influenza Virus

Influenza is a single-stranded, helically shaped, RNA virus of the 

orthomyxovirus family. Three types of influenza virus are known 

to affect humans: A, B, and C. Type A influenza has subtypes 

determined by the surface antigens hemagglutinin (HA) and 

neuraminidase (NA). There are 18 different H subtypes and 11 

different N subtypes. Eight H subtypes (H1, H2, H3, H5, H6, H7, 

H9, H10) and six N subtypes (N1, N2, N6, N7, N8, and N9) have 

been detected in humans. Type B influenza is classified into two 

lineages: B/Yamagata and B/Victoria.

Infection with influenza viruses can be asymptomatic or 

result in disease that ranges from mild to severe. Influenza 

B more commonly affects children. Influenza C is rarely 

reported as a cause of human illness, probably because most 

cases are subclinical. Influenza C has not been associated 

with epidemic disease.

Antigenic Changes

Virus surface antigens hemagglutinin and neuraminidase 

continually change. Changes in influenza viruses can take the 

form of antigenic drift or antigenic shift. 

Antigenic drift involves small mutations in the genes of 

influenza viruses that lead to changes in HA and NA that 

accumulate over time, resulting in the emergence of novel 

strains that the human immune system may not recognize. 

These novel strains are the influenza virus’s evolutionary 

adaptations to a strong population-wide immune response. 

Elisha Hall, PhD, RD

Influenza

● Viral illness

● First pandemic in 1580

● Estimated 21 million deaths

worldwide in pandemic

of 1918-1919

● Influenza A and B viruses

isolated in the 1930s

● Inactivated vaccines first

developed and used in the

late 1930s and 1940s

Influenza Virus

● Single-stranded RNA virus

● Orthomyxovirus family

● Three types affect humans:

A, B, C

● Infection can be asymptomatic

or result in mild to severe disease

Antigenic Changes

● Antigenic drift

■ Small mutations over time

that result in novel strain

■ Primary reason people

can get influenza more

than once

■ May result in annual

influenza epidemic

● Antigenic

■ Abrupt, major change in

surface antigen(s)

■ May lead to pandemic (rare)

https://www.cdc.gov/vaccines/pubs/pinkbook/flu.html Aug 2021
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Antigenic drift is the primary reason people can get influenza 

more than once and why it is necessary to annually review 

and update the composition of influenza vaccines. Antigenic 

drift, along with waning immunity, results in annual influenza 

epidemics, since the protection that remains from past 

exposures to similar viruses is incomplete. Drift occurs in all 

three types of influenza virus (A, B, C). 

Antigenic shift involves an abrupt, major change in one or 

both surface antigens (H or H-N combination). Antigenic shifts 

are probably due to genetic recombination (an exchange of a 

gene segment) between influenza A viruses that affect humans 

and/or animals. An antigenic shift may result in a worldwide 

pandemic if the virus is efficiently transmitted from person to 

person. Pandemics are rare; since the late 19th century, five 

antigenic shifts have led to pandemics in 1889-1891, 1918-1920, 

1957-1958, 1968-1969, and 2009-2010.

Pathogenesis

Following respiratory transmission, the virus attaches to and 

penetrates respiratory epithelial cells in the trachea and bronchi. 

Viral replication occurs, which results in the destruction of the 

host cell. Regeneration of epithelium takes about 3 to 4 weeks. 

Viremia, or presence of virus in the blood, has rarely been 

documented. Virus is shed in respiratory secretions for 5 to 10 

days, with a peak of 1 to 3 days following illness onset.

Clinical Features

The incubation period for influenza is usually 2 days but 

can vary from 1 to 4 days. Influenza illness can range from 

asymptomatic to severe infection. On average, about 8% of the 

U.S. population gets sick from influenza each season (range 

between 3% and 11%). 

Onset of influenza symptoms is sudden. Respiratory symptoms 

include cough, sore throat, and runny or stuffy nose. Systemic 

symptoms generally include fever, chills, headache, malaise, 

and myalgia. Vomiting and diarrhea may also occur, especially 

in children. Recovery is rapid; fever usually resolves within 3 

to 4 days and other symptoms within approximately 7 days. 

Some patients may have lingering asthenia (lack of strength or 

energy) for several weeks. More information can be found at: 

www.cdc.gov/flu/symptoms/symptoms.htm. 

Influenza symptoms (e.g., pain and fever) can be controlled 

with medications such as aspirin, ibuprofen, or acetaminophen. 

Aspirin and salicylate-containing products should not be used 

for children or adolescents because it may increase the risk for 

developing Reye syndrome. 

Influenza Pathogenesis

● Respiratory transmission

● Replication in respiratory

epithelium with subsequent

destruction of cells

● Viremia rarely documented

● Virus shed in respiratory

secretions for 5–10 days

Influenza Clinical Features

● Incubation period 2 days (range,

1–4 days)

● About 8% of U.S. population

gets sick each season

● Sudden onset of symptoms

■ Respiratory: cough, sore

throat, runny or stuffy nose

■ Systemic: fever, chills,

headache, malaise, myalgia

■ Gastrointestinal: vomiting,

diarrhea

● Rapid recovery
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Complications

People most at risk of developing serious influenza-related 

complications include people age 65 years and older, people 

with chronic medical conditions (e.g., heart disease or diabetes), 

pregnant women, and young children, especially those younger 

than age 2 years. More common complications of influenza 

include secondary bacterial pneumonia (e.g., Streptococcus 

pneumoniae, Haemophilus influenzae, or Staphylococcus aureus), 

exacerbations of underlying respiratory conditions, otitis media, 

laryngotracheobronchitis, and bronchitis. 

Other complications may include primary pneumonia, 

encephalitis, aseptic meningitis, transverse myelitis, myocarditis, 

pericarditis, Guillain-Barré syndrome, and Reye Syndrome. Reye 

syndrome is a complication that occurs almost exclusively in 

children taking aspirin, primarily in association with influenza 

B virus (or varicella zoster virus), and presents with severe 

vomiting and confusion, which may progress to coma due to 

swelling of the brain. 

Most deaths due to influenza typically occur among persons 

age 65 years and older. 

Laboratory Testing

Influenza is usually suspected based on characteristic clinical 

findings, particularly if influenza has been reported in the 

community. Influenza virus testing is not required to make a 

clinical diagnosis but can inform clinical management when 

results may influence decisions to initiate antiviral treatment, 

perform other diagnostic testing, or implement infection and 

prevention control measures. Diagnostic tests include:

• Molecular assays (i.e., rapid molecular assays, reverse 

transcription polymerase chain reaction (RT-PCR), and other 

nucleic acid amplification tests)

• Antigen detection tests (i.e., rapid influenza diagnostic 

tests and immunofluorescence assays)

Approved respiratory tract specimens differ among the 

FDA-cleared influenza tests, so clinicians should refer to the 

specific test’s package insert for approved respiratory specimens.

In addition to diagnostic testing for only influenza virus, the 

Flu SC2 Multiplex Assay is a real-time RT-PCR test that detects 

and differentiates RNA from SARS-CoV2, influenza A virus, and 

influenza B virus in upper or lower respiratory specimens.

Serology testing is no longer used for clinical diagnosis of 

influenza but is still used for research studies. 

Influenza Complications

● Secondary bacterial pneumonia

● Exacerbations of underlying 

respiratory conditions

● Otitis media

● Laryngotracheobronchitis

● Bronchitis

● Other less common 

complications may occur
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Information for health care providers on influenza virus testing 

can be found at www.cdc.gov/flu/professionals/diagnosis/index.

htm. Details about the laboratory diagnosis of influenza are 

available at www.cdc.gov/flu/symptoms/testing.htm.

Medical Management

Vaccination is the principal means for preventing influenzarelated morbidity and mortality, however antiviral agents may 

be indicated in some situations for preventing and/or treating 

influenza. Current recommendations and a decision tree for 

clinicians is available for making antiviral decisions: 

https://www.cdc.gov/flu/professionals/antivirals/summaryclinicians.htm

Epidemiology

Occurrence

Influenza occurs throughout the world.

Reservoir

Humans are the only known reservoir of influenza type C. 

Influenza B generally infects humans, but at least two reports 

have documented influenza B in seals. Influenza A viruses may 

infect both humans and some animals. Examples of animals 

include, but are not limited to, wild birds, poultry, pigs, horses, 

mink, and ferrets. There is no chronic carrier state.

Transmission

Influenza is primarily transmitted from person to person via 

large, virus-laden droplets (more than 5 microns in diameter) 

that are generated when infected persons cough or sneeze. 

These large droplets can then settle on the mucosal surfaces 

of the upper respiratory tracts of susceptible persons who are 

within six feet of infected persons. Aerosol transmission of small 

droplets may also transmit influenza. Transmission may occur 

through direct or indirect contact with respiratory secretions, 

such as when touching surfaces contaminated with influenza 

virus and then touching the eyes, nose, or mouth. 

Temporal Pattern

In the Northern Hemisphere, influenza season can begin as 

early as October and last as late as April or May, while in the 

Southern Hemisphere, the season typically occurs during AprilSeptember. Influenza occurs throughout the year in tropical 

areas. In the United States, for 75% of influenza seasons from 

the 1982–1983 through the 2017–2018 season, peak influenza 

activity has not occurred until January or later. In 58% of 

seasons, the peak was in February or later. 

Influenza Epidemiology

● Reservoir

■ Type A infects humans and 

some animals

■ Type B generally infects 

humans

■ Type C infects only humans

● Transmission

■ Person-to-person via large 

droplets

■ Aerosol transmission of small 

droplets

■ Exposure to fomites

● Temporal pattern 

■ October–April or May in 

northern hemisphere

■ April–September in southern 

hemisphere

■ Year round in tropical climates

● Communicability

■ 1 day before to 5 to 7 days 

after (adults) or 10 days after 

onset (children)
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Communicability

Adults can transmit influenza from the day before symptom 

onset to approximately 5 to 7 days after symptoms begin. 

Children can transmit influenza to others for 10 or more days 

after symptoms begin.

Secular Trends in the United States

Symptomatic illness of influenza is common. CDC estimates 

that between 9.3 million and 45 million people experience 

symptomatic illness annually. An increase in mortality typically 

accompanies each annual influenza season. Increased mortality 

results not only from influenza and pneumonia, but also from 

cardiopulmonary and other chronic diseases that can be 

exacerbated by influenza.

The number of influenza-associated deaths varies substantially 

by year, influenza virus type and subtype, and age group. Since 

2010, CDC estimates the number of annual influenza-associated 

deaths has ranged from a low of 12,447 (2011–2012 season) to 

a high of 61,099 (2017–2018 season), with an average of 37,463 

influenza-associated deaths annually. Persons age 65 years and 

older account for approximately 80% of deaths attributed to 

influenza. While relatively rare, some children die from influenza 

each year. The 2019-2020 influenza season marked the highest 

recorded number for pediatric influenza deaths during a regular 

season at 189 reported pediatric influenza deaths.

The risk for complications and hospitalizations from influenza 

is higher among persons age 65 years and older, pregnant and 

post-partum women, children younger than age 5 years, and 

persons of any age with certain underlying medical conditions. 

Since 2010, an average of more than 445,000 hospitalizations 

per year have been related to influenza, with about 38% 

occurring in persons younger than age 65 years. 

Influenza causes more hospitalizations among young children 

than any other vaccine-preventable disease. CDC estimates 

that since 2010, influenza-related hospitalizations among 

U.S. children younger than age 5 years have ranged from 

7,000 to 26,000 each year. Healthy children age 5 through 18 

years are not at increased risk for influenza complications. 

However, children typically have the highest attack rates during 

community outbreaks of influenza and serve as a major source 

of influenza transmission within communities. 

During the 2019–2020 influenza season, 75.5% of children age 6 

months–4 years and 64.6% of children age 5–12 years received 

the influenza vaccine. Coverage was 53.3% for adolescents age 

13 through 17 years. Among adults age 18 through 64 years and 

age 65 years and older, 42.3% and 69.8% received the influenza 

vaccine, respectively. Coverage in all age groups increased from 

the 2018–2019 season, with the largest increase (3.3%) in adults 

Influenza Secular Trends 

in the United States

● 9.3 to 45 million people 

experience symptomatic 

illness annually

● Annual average of 37,463 

influenza-associated deaths 

since 2010

● Groups at risk for 

complications and 

hospitalizations include: 

■ Persons age 65 years 

and older

■ Pregnant and post-partum 

women

■ Children younger than 

age 5 years

■ Persons with certain 

underlying medical conditions

● Causes more hospitalization 

among young children 

than any other vaccinepreventable disease
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age 18 through 64 years. During 2019–2020, 61.2% of pregnant 

women received influenza vaccination.

CDC estimates that vaccination in the U.S. during 2010–2011 

through 2017–2018 seasons averted an estimated 4.9 million 

symptomatic illnesses, 2.4 million medical visits, 70,000 

hospitalizations, and 6,400 deaths. Adults age 65 years 

represented a majority of the averted deaths (80%) and 

hospitalizations (58%). Children age 6 months to 17 years 

represented 43% of averted symptomatic illness and 51% of 

averted medical visits.

Pandemics

Since the late 19th century, five antigenic shifts have led to 

pandemics. Typically during influenza pandemics, there are high 

attack rates involving all age groups, and mortality is usually 

markedly increased. Severity is generally not greater in the 

individual patient (except for during the 1918–1919 pandemic), 

but because large numbers of persons are infected, there will 

be a large number of severe and fatal cases. Onset may occur in 

any season of the year. Secondary and tertiary waves may occur 

up to two years later, usually in the winter. 

In January 2011, CDC estimated that the 2009 H1N1 caused 

illness in more than 60 million Americans, leading to more than 

270,000 hospitalizations and 12,500 deaths. Contrary to typical 

seasons, ninety percent of hospitalizations and deaths occurred 

in persons younger than age 65 years.

Influenza Vaccines

Vaccine composition is reviewed and updated each year since 

the influenza virus is constantly changing. Considerations 

include which influenza viruses are causing illness, the extent to 

which viruses are spreading, and how well the previous season’s 

vaccine protects against those viruses. 

Three types of influenza vaccine are available in the United 

States: inactivated influenza vaccine (IIV); live, attenuated 

influenza vaccine (LAIV); and recombinant influenza vaccine 

(RIV). Trivalent vaccine contains three inactivated viruses: type 

A(H1N1), type A(H3N2), and type B. Quadrivalent influenza 

vaccines were first introduced during the 2013–2014 season. 

They contain the same antigens as trivalent vaccines, with an 

additional type B strain. 

ACIP does not recommend use of any influenza vaccine outside 

the vaccine’s FDA-approved age indication. Information about 

current influenza vaccines and recommendations from the 

Advisory Committee on Immunization Practices (ACIP) are 

updated annually. For current information, see https://www.cdc.

gov/vaccines/hcp/acip-recs/vacc-specific/flu.html.

Influenza Vaccines

● Vaccine composition reviewed 

and updated each year, for 

current information see: https://

www.cdc.gov/vaccines/hcp/

acip-recs/vacc-specific/flu.html

■ Inactivated influenza 

vaccine (IIV)

■ Live, attenuated influenza 

vaccine (LAIV)

■ Recombinant influenza 

vaccine (RIV)
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Characteristics

Inactivated Influenza Vaccines (IIV)

IIV has been available since the 1940s. Most influenza vaccines 

distributed in the United States are subvirion (split-virus) 

or subunit inactivated vaccines. IIV currently licensed and 

distributed in the United States is administered by the 

intramuscular route. Vaccines are available in multiple 

presentations (manufacturer-filled syringe, single-dose vials, 

and multidose vials) and in preservative-free formulations. 

Viruses for IIV are grown in either chicken eggs (egg-based) 

or cell culture (cell culture-based). The final products from 

egg-based IIV contain residual egg protein. Thimerosal may be 

used in some influenza vaccines as a preservative to prevent 

microbial growth. The FDA package inserts can be referenced 

annually for the most current influenza vaccine ingredients. 

Recombinant Influenza Vaccine (RIV) 

RIV was first approved for use in 2013. The RIV manufacturing 

process uses recombinant DNA technology and does not 

require an egg-grown vaccine virus. The resulting vaccine 

contains recombinant hemagglutinin. 

Live, Attenuated Influenza Vaccine (LAIV)

LAIV was first approved for use in the United States in 2003. The 

vaccine viruses are grown in chicken eggs and the final product 

contains residual egg protein. The viruses are cold-adapted 

and replicate effectively in the mucosa of the nasopharynx. 

LAIV is administered intranasally. The vaccine is provided in a 

manufacturer-filled, single use, intranasal sprayer; half of the 

dose is sprayed into each nostril. Vaccinated children can shed 

vaccine viruses in nasopharyngeal secretions for up to 3 weeks. 

Transmission of shed LAIV viruses from vaccine recipients to 

unvaccinated persons has been documented but has not been 

reported to be associated with serious illness. 

Vaccination Schedule and Use

Influenza vaccination is recommended annually for persons 

age 6 months and older who do not have contraindications. 

Vaccination is particularly important for persons at increased 

risk for severe illness and complications from influenza. 

When vaccine supply is limited, efforts should focus on 

delivering vaccination to high-risk groups who do not 

have contraindications. Emphasis should also be placed on 

vaccination of persons who live with or care for those who are 

at increased risk (e.g., healthcare personnel).

Influenza activity can begin as early as October and last as late 

as April or May, but most frequently peaks in January. To ensure 

maximum protection, vaccination should be administered 

before the onset of influenza activity in the community. 

Influenza Vaccine Characteristics

● IIV

■ Administered by 

intramuscular injection

■ Multidose vials contain 

thimerosal

■ Some products contain 

residual egg protein

● RIV

■ Administered by 

intramuscular injection

■ Does not contain egg protein

● LAIV

■ Administered intranasally

■ Contains residual egg protein

Influenza Vaccination Schedule

● 1 dose each influenza season 

for persons age 9 years or older

● 1 or 2 doses each influenza 

season for children age 6 

months through 8 years 

■ 1 dose if 2 or more doses are 

documented prior to July 1

■ 2 doses administered at least 

4 weeks apart if 2 or more 

doses are not documented 

prior to July 1

● Refer to ACIP recommendations 

each season for most 

recent schedule
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However, varied timing of onset, peak, and duration of influenza 

season, as well as potential vaccine-induced immunity waning, 

make it difficult to determine the ideal time to administer 

vaccine for each season. CDC recommends influenza vaccination 

by the end of October. However, vaccine should continue to be 

offered throughout the influenza season, even into January or 

later. Getting vaccinated early (e.g., July or August) is likely to be 

associated with reduced protection against influenza infection 

later in the influenza season, particularly among older adults.

IIV and RIV should be administered by intramuscular injection. 

Both IIV and RIV may be administered on the same day or any 

time before or after other inactivated vaccines or live vaccines. 

If given on the same day with other injectable vaccines, the 

vaccines should be administered at separate anatomic sites. 

LAIV should be administered intranasally. It may be given on the 

same day with other live or inactivated vaccines. If LAIV is not 

administered on the same day with other live vaccines, then at 

least 4 weeks should separate administration of LAIV and other 

live vaccines.

Persons age 9 years or older should receive 1 dose of a 

licensed age-appropriate vaccine each influenza season. 

Children age 6 months through 8 years who do not have 

documentation showing receipt of 2 or more doses of any 

influenza vaccine prior to July 1 should receive 2 doses of a 

licensed age-appropriate vaccine. This 2-dose series should be 

administered at least 4 weeks apart. 

Immunogenicity and Vaccine Efficacy

For practical purposes, the duration of immunity following 

influenza vaccination is less than one year because of vaccineinduced antibody waning and antigenic drift of circulating 

influenza viruses. Influenza vaccine effectiveness depends on 

many factors including the similarity of the vaccine strain(s) 

to the circulating strain(s), the age and health status of the 

recipient, and the type of vaccine administered. Vaccination is 

effective in reducing the risk of influenza illness by 40% to 60% 

in the overall population when vaccine strains and circulating 

viruses are similar. However, the vaccine can be less effective in 

preventing illness among persons age 65 years and older.

During the 2010–2011 to 2018–2019 influenza seasons, 

adjusted overall vaccine efficacy has ranged from 19% to 

60% in patients age 6 months and older. Circulating A/H3N2 

influenza viruses drifted significantly after strain selection 

for the 2014–2015 vaccines, contributing to a lower vaccine 

efficacy of 19% during that season.

Studies have demonstrated a variety of benefits to influenza 

vaccination, including fewer: Illnesses, medical visits, ICU and 

hospital admissions, and days in the ICU and hospital. Fewer 

Influenza Vaccine Efficacy 

● Duration of immunity less than 

one year due to waning and 

antigenic drift

● 40% to 60% effective in 

reducing the risk of influenza

■ Effectiveness depends on 

similarity of vaccine strain(s) 

to circulating strain(s), age 

and health status of 

recipient, and type of 

vaccine administered
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deaths have been demonstrated only in children. Additionally, 

some studies show that severity of illness among vaccinated 

persons who become sick is reduced. Influenza vaccination has 

also been associated with positive outcomes for people with 

chronic health conditions (e.g., lower rates of cardiac events 

among people with heart disease) and pregnant women (e.g., 

reduced risk of hospitalization and acute respiratory infection).

A number of influenza vaccines from different manufacturers 

are available each season. Where there is more than one 

influenza vaccine available that is appropriate for a given 

recipient, ACIP does not express a preference for any one 

vaccine over another.

Contraindications and Precautions 

to Vaccination

Inactivated Influenza Vaccine (IIV) and 

Recombinant Influenza Vaccine (RIV)

As with other vaccines, a history of severe allergic reaction 

(anaphylaxis) to a vaccine component or following a prior 

dose is a contraindication to further doses. Moderate or severe 

acute illness (with or without fever) in a patient is considered a 

precaution to vaccination, although persons with minor illness 

may be vaccinated. 

History of Guillain-Barré syndrome within 6 weeks of receipt of 

influenza vaccine is a precaution to vaccination for all influenza 

vaccines licensed in the United States. 

Because vaccine composition is reviewed and updated 

each year, refer to ACIP’s most recent recommendations for 

contraindications and precautions: https://www.cdc.gov/

vaccines/hcp/acip-recs/vacc-specific/flu.html.

Live, Attenuated Influenza Vaccine (LAIV) 

LAIV has additional contraindications and precautions. Refer to 

ACIP’s most recent recommendations for LAIV contraindications 

and precautions: https://www.cdc.gov/vaccines/hcp/acip-recs/

vacc-specific/flu.html.

Vaccine Safety

Inactivated Influenza Vaccine (IIV)

Studies support the safety of annual IIV vaccination in children 

and adults. Local reactions are the most common adverse 

reactions following vaccination with IIV. These include soreness, 

redness, tenderness, or swelling at the injection site. These 

reactions are transient, generally lasting 1 to 2 days. In clinical 

trials, pain at the injection site during the first week after 

vaccination occurred in up to 65% of people vaccinated with IIV. 

Influenza Vaccine Contraindications 

and Precautions (IIV and RIV)

● Contraindication 

■ Severe allergic reaction 

to vaccine component or 

following a prior dose 

● Precaution

■ Moderate or severe 

acute illness

■ History of Guillain-Barré 

syndrome (GBS) within 

6 weeks of receipt of 

influenza vaccine

● Refer to ACIP influenza 

vaccine recommendations 

for LAIV contraindications 

and precautions
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Influenza

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Nonspecific systemic symptoms, including fever, chills, malaise, 

and myalgia, occur less often. These symptoms usually occur 

in those with no previous exposure to the viral antigens in 

the vaccine. Symptoms usually occur within 6 to 12 hours of 

IIV vaccination and last 1 to 2 days. Recent reports indicate 

systemic symptoms are no more common after receipt of IIV 

than in persons given a placebo injection. 

In some influenza seasons, IIV has been associated with an 

increased risk for febrile seizures on the day of, and the day after 

vaccination in young children. Febrile seizure is more likely to 

occur if IIV is given on the same day as 13-valent pneumococcal 

conjugate vaccine (PCV13) and diphtheria, tetanus, and acellular 

pertussis (DTaP) vaccines. Most febrile seizures are brief and 

have a good prognosis. ACIP reviewed the risks and benefits of 

febrile seizures after IIV and did not make any changes in the 

recommendations for administering pediatric vaccines; these 

vaccines can be given on the same day.

Guillain-Barré syndrome (GBS), a serious neurological condition 

that can cause paralysis, is known to occur after multiple 

infectious illnesses, particularly gastrointestinal and upper 

respiratory infections. GBS is known to occur rarely after 

influenza illness. Safety monitoring of seasonal IIV over the 

course of many years has not detected a clear link to GBS. If 

there is a risk of GBS from IIV, it would be no more than 1 to 2 

cases per million people vaccinated. Studies suggest that the 

risk of GBS after influenza illness is higher than the potential risk 

of developing GBS after vaccination. 

Recombinant Influenza Vaccine (RIV)

Studies support the safety of RIV in adults. During the 

pre-licensure clinical trials for RIV, the most common 

injection-site reaction for adults age 18 through 49 years were 

tenderness (48%) and pain (37%); the most common solicited 

systemic adverse reactions were headache (20%), fatigue 

(17%), and muscle pain (13%). Two serious adverse events 

(pleuropericarditis and vasovagal syncope) were assessed as 

possibly related to RIV vaccination. After licensure, a review 

of reports to the Vaccine Adverse Event Reporting System 

(VAERS) from 2013–2016 found 88 reports; allergic reactions 

were the most common adverse event reported. Other adverse 

events reported were injection site reactions, fatigue, myalgia, 

headache, and fever. There were four serious reports but no 

death was reported. 

Live, Attenuated Influenza Vaccine (LAIV)

Studies support the safety of LAIV. In pre-licensure clinical trials, 

the most common adverse reactions were runny nose or nasal 

congestion in all ages, fever in children age 2 through 6 years, 

and sore throat in adults. Clinical trials show LAIV4 has a safety 

Influenza Vaccine Safety

IIV

● Soreness, redness, tenderness, 

or swelling at the injection 

site is common

● No clear link with GBS; risk 

would be no more than 

1 to 2 cases per million

RIV

● Tenderness

■ 48%

● Pain

■ 37%

● Headache

■ 20%

● Fatigue

■ 17%

● Muscle pain

■ 13%

LAIV

● Runny nose, nasal 

congestion (children)

● Sore throat, headache, 

tiredness/weakness, 

muscle aches, cough, chills, 

sinusitis (adults)
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profile similar to the previously used trivalent LAIV, with the 

exception of slightly more reports of fever after the first dose of 

LAIV4 compared to trivalent LAIV in children age 2 through 8 

years who were getting vaccinated for the first time. In adults, 

other adverse events reported more often after LAIV than 

after placebo were headache, sore throat, tiredness/weakness, 

muscles aches, cough, chills, and sinusitis.

Limited data are available concerning the safety of LAIV 

among persons at high risk for influenza complications, such as 

immunosuppressed persons or those with chronic pulmonary 

or cardiac disease. Therefore, persons at high risk of influenza 

complications should receive IIV rather than LAIV.

Vaccination During Pregnancy

Pregnant women are at an increased risk for severe illness and 

complications from influenza due to changes in immunologic, 

heart and lung function. In addition, some studies suggest 

influenza infection is associated with preterm delivery and 

fetal demise. ACIP and the American College of Obstetricians 

& Gynecologists recommend women who are pregnant, might 

be pregnant, or are up to two weeks postpartum during the 

influenza season should receive any licensed, age-appropriate 

IIV or RIV product. LAIV is contraindicated during pregnancy. 

Vaccination can occur at any time during pregnancy, before and 

during the influenza season.

Vaccine Storage and Handling

Influenza vaccines (IIV, RIV, and LAIV) should be maintained at 

refrigerator temperature between 2°C and 8°C (36°F and 46°F). 

LAIV sprayers must be kept in the carton until use in order to 

protect from light. For complete information on best practices 

and recommendations, please refer to CDC’s Vaccine Storage 

and Handling Toolkit, www.cdc.gov/vaccines/hcp/admin/

storage/toolkit/storage-handling-toolkit.pdf. 

Surveillance and Reporting of Influenza

Influenza-associated deaths among children younger than 

age 18 years and human infection with a novel influenza A 

virus are nationally notifiable conditions reported through 

the National Notifiable Diseases Surveillance System (NNDSS). 

Other influenza virus infections are not nationally notifiable but 

may be reported in some states. Influenza surveillance in the 

U.S. consists of five categories of information, including viral, 

outpatient illness, mortality, and hospitalization surveillance, as 

well as summary of the geographic spread of influenza. 

Influenza surveillance is intended to monitor the prevalence of 

circulating strains and detect new strains necessary for vaccine 

formulation; estimate influenza-related impact on morbidity, 
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 12

mortality, and economic loss; rapidly detect outbreaks; and 

assist disease control through rapid preventive action (e.g., 

chemoprophylaxis of unvaccinated high-risk patients).

For information on guidance for state and local health 

department staff who are involved in surveillance activities for 

vaccine-preventable diseases, please consult the Manual for the 

Surveillance of Vaccine-Preventable Diseases, www.cdc.gov/

vaccines/pubs/surv-manual/chapters.html. 

Acknowledgements

The editors would like to acknowledge Scott Epperson,

 Lisa Grohskopf, David Shay, Tom Shimabukuro, and 

Jerome Tokars for their contributions to this chapter.

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