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Influenza Overview


Quick Facts

Influenza


Click the image above to learn how to stay healthy this flu season and about the influenza vaccine.
  • Influenza, often referred to as “flu,” is a viral respiratory disease caused by type A or type B influenza viruses, which constantly mutate, and are infectious in humans and animals.1  Different influenza strains cause outbreaks and epidemics and, infrequently, cause pandemics that spread globally and are usually associated with more severe disease and increased mortality. Historically, influenza pandemics have involved type A influenza strains like the one that caused the 1918-19 influenza pandemic.2  
  • Symptoms of influenza include fever, chills, headache, sore throat, runny or stuffy nose, coughing, sneezing, and sometimes vomiting and diarrhea. Serious complications of influenza infection include dehydration, bronchitis, bacterial or viral pneumonia, otitis media (ear infection) and, in very severe cases, death. The majority of people recover from type A or B influenza without serious complications. The elderly, very young children, pregnant women and persons with certain chronic diseases, like asthma and heart or lung disease, are at higher risk for influenza complications. 3  
  • Over 80 percent of all respiratory infections that occur during the “flu season” are not type A or type B influenza because there are many other viruses and bacteria that can cause respiratory “influenza-like illness” (ILI). ILI infection symptoms are similar to influenza symptoms and only lab tests can confirm whether an individual has been infected by influenza or an ILI. 4 5
  • Influenza viruses are primarily spread through coughing and sneezing. Public health officials say that, for a limited period of time, influenza can also be transmitted if an uninfected person touches or uses items that have been recently handled by an infected person. 6  
  • Frequent hand washing; covering the mouth while coughing; staying home when sick and avoiding contact with infected individuals; staying hydrated and eating nutritious food; lowering stress and getting plenty of exercise; sleep and vitamin D are helpful in the preventing influenza and ILI infections. 7 8 9 10

Influenza (Flu) Vaccines 

  • There are several different influenza vaccines licensed by the U.S. Food and Drug Administration (FDA) and distributed by manufacturers for use in the U.S. that are recommended by the US Centers for Disease Control (CDC) for different age groups.11  Most seasonal influenza vaccines in the U.S. contain either two type A influenza viruses and one type B influenza virus (Trivalent) or two type A influenza viruses and two type B influenza viruses (Quadrivalent) that are selected every year by the World Health Organization (WHO) and U.S. Centers for Disease Control (CDC) for inclusion in influenza vaccines given during the current flu season.12
  • Most of the influenza vaccines in use in the U.S. are injectable, inactivated vaccines that are made using chicken embryos, insect cells, or dog kidney cells. Depending upon the vaccine manufacturer, some influenza vaccines contain an oil in water squalene adjuvant that hyper-stimulates the immune system to produce a stronger antibody response. 13 Injectable influenza vaccines packaged in multi-dose vials contain the mercury preservative thimerosal, and inactivated influenza vaccines packaged in single dose vials are either thimerosal-free or contain trace amounts of the mercury preservative, while the live attenuated nasal vaccine contains no thimerosal. 14 During the 2016/17 and 2017/18 flu seasons, the CDC’s Advisory Committee on Immunization Practices (ACIP) withdrew its recommendation for use of the nasal spray influenza vaccine after analyzing data demonstrating it failed to prevent influenza infection most of the time.15 However, in February 2018, ACIP reversed its decision and voted to approve a new formulation of the nasal spray influenza vaccine for the 2018-2019 influenza season. This decision was made despite the lack of vaccine efficacy studies to support whether this vaccine will offer any improved protection from influenza. 16  
  • The CDC recommends that all Americans six months of age or older get a flu shot every year and that babies between six and eight months old receive two doses of influenza vaccine one month apart in the first year of life. 17 The CDC reports that between 2004/2005 and 2017/2018, overall influenza vaccine effectiveness ranged from 10 percent (2004/2005) to 60 percent (2010/2011) and the vaccine was less than 50 percent effective in 10 out of 14 flu seasons.
  • Using the MedAlerts search engine, as of May 31, 2019, there have been more than 166,178 reports of influenza vaccine reactions, hospitalizations, injuries and deaths following influenza vaccinations made to the federal Vaccine Adverse Events Reporting System (VAERS), including 1,673 related deaths, 13,373 hospitalizations, and 3,358 related disabilities. Moderate reactions reported include fever, local reactions (pain, redness, swelling at the site of the injection), headache, fatigue, sore throat, nasal congestion, cough, joint and muscle pain, and nausea. Serious vaccine complications include brain inflammation and neurological damage, convulsions, Bell’s palsy, limb paralysis, neuropathy, shock, wheezing/asthma and other breathing problems, and death. Influenza vaccinations can cause Guillain Barre Syndrome (GBS), a painful and disabling immune and neurological disorder of the peripheral nervous system that can cause temporary or permanent paralysis and death.
  • In 2013, the Federal Advisory Commission on Childhood Vaccines (ACCV) voted to add GBS to the Vaccine Injury Table (VIT) within the federal Vaccine Injury Compensation Program (VICP) and it was officially added in 2017. As of Sept 1, 2019, there have been 5,560 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following influenza vaccination, including 174 deaths and 5,386 serious injuries.

Food & Drug Administration (FDA)

  • Adjuvanted Influenza Vaccine Product Inserts & Licensing Information
  • Live Trivalent and Quadrivalent Intranasal Influenza Vaccine Product Insert & Licensing Information
  • Attenuated Trivalent and Quadrivalent Injectable Influenza Vaccine Product Insert & Licensing Information

Centers for Disease Control (CDC)

National Institute of Allergy & Infectious Diseases (NIAID)

NIAID on Influenza

Vaccine Reaction Symptoms & Ingredients

NVIC’s Ask 8, If You Vaccinate webpage contains vaccine reaction symptoms and you can download a Know the Facts to Stay Healthy This Flu Season brochure.

Search for Vaccine Reactions

NVIC hosts MedAlerts, a powerful VAERS database search engine. MedAlerts examines symptoms, reactions, vaccines, dates, places, and more.

Reporting a Vaccine Reaction

Since 1982, the NVIC has operated a Vaccine Reaction Registry, which has served as a watchdog on VAERS. Reporting vaccine reactions to VAERS is required by federal law under the National Childhood Vaccine Injury Act of 1986. If your doctor will not report a reaction, you have the right to report a suspected vaccine reaction to VAERS.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Influenza and the Influenza vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

« Return to Vaccines & Diseases Table of Contents

What is Influenza?     

Influenza is a viral infection that produces fever, chills, sore throat, muscle aches, and cough that lasts a week or more.18  People tend to use the term "flu" to describe any kind of respiratory or gastrointestinal illness, such as colds or diarrhea and vomiting that resemble “influenza-like-illness” (ILI) symptoms. But influenza is usually associated with more severe illness and lasts longer than the common cold and, normally, influenza does not cause vomiting or diarrhea in adults.19

Influenza viruses are RNA genome viruses in the Orthomyxoviridae family. Influenza A viruses infect humans, animals and birds and influenza B and C viruses mainly infect humans, while influenza type D infects cattle. According to the World Health Organization (WHO), “influenza virus undergoes high mutation rates and frequent genetic reassortment (combination and rearrangement of genetic material) leading to variability in HA (haemagglutinin) and NA (neuraminidase) antigens.” 20

Influenza A viruses are found in ducks, chickens, pigs, horses, whales and seals. Wild birds are the primary natural reservoir for influenza A viruses and often cause asymptomatic or mild infection in birds but can become virulent in both wild and domestic poultry (chickens, turkeys). Pigs can be infected with swine, human and bird (avian) viruses and sometimes those viruses recombine and create new influenza viruses.21 22 Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus and can be further broken down into different strains, while influenza B viruses are not divided into subtypes but can be broken into lineages and strains.23

Because influenza viruses are constantly mutating and there are different strains and subtypes that are more or less prevalent among human populations from year to year, outbreaks and epidemics occur in certain geographical areas or countries. Occasionally, an influenza strain will emerge to cause an influenza pandemic that spreads globally and is usually associated with more severe disease and increased mortality.24 Historically, influenza pandemics with higher rates of complications and death have involved type A influenza strains like the one that caused the 1918-19 influenza pandemic.25

Over 80 percent of all respiratory infections that occur during the “flu season” are not type A or type B influenza because there are many other viruses and bacteria that can cause respiratory “influenza-like illness” (ILI). ILI infection symptoms are similar to influenza symptoms and only lab tests can confirm whether an individual has been infected by influenza or an ILI. 26 27

The vast majority of people recover from influenza without any complications and develop immunity to future infection with the same strain or a related influenza strain that may prevent illness symptoms or make illness less severe. There is, however, an increased risk for serious complications and death for the elderly and those with compromised immune systems or who are suffering from diabetes, kidney dysfunction, heart disease, and other chronic health issues.28

Between the 1976/1977 and 2006/2007 flu seasons, the Centers for Disease Control (CDC) estimated that, depending upon the influenza type and strain circulating in a given year, influenza-related deaths in the United States range between a low of 3,000 and a high of 49,000.29 According to the CDC, between 2010 and 2018 influenza-associated deaths have ranged between a low of 12,000 to a high of 79,000. 30 These numbers, however, are only estimates because the CDC does not collect influenza-related death information for persons 18 years and older so the exact number remains unknown.31

Is Influenza contagious?   

A viral infectious disease, influenza is contagious and can last 3 to 14 days if complications do not occur.32 Most healthy adults are thought to be infectious and able to shed influenza virus and transmit it to others beginning one day before symptoms develop and for five to seven days after becoming ill. It is estimated that some children may be infectious for longer than seven days.33  Severely immunocompromised children and adults may shed influenza virus for weeks or months.34

Both vaccinated and unvaccinated persons can be infected with and shed and transmit influenza virus in respiratory secretions35 and wild-type influenza virus has also been shed and identified in stool.36 Vaccinated and unvaccinated individuals can transmit influenza to others but be asymptomatic and have no apparent clinical symptoms themselves.37 38

Influenza viruses are transmitted through the air by droplets when infected persons cough, sneeze or talk. These droplets can end up in the mouths or noses or inhaled into the lungs of others near a person with influenza.39 Less frequently, a person might also become infected when touching an item or surface with influenza virus on it and then touching their own nose or mouth.40

To avoid transmitting influenza virus – or other types of influenza-like respiratory infections - to others, people who know they are sick should stay home until they are well. Frequent hand washing with soap and water can help prevent the spread of influenza and other viruses. If soap and water is not available, alcohol-based hand sanitizers can also be used. Eating utensils, dishes, linens and other personal items used by those who are sick should not be shared without thorough washing. Surfaces that are frequently touched should be cleaned and disinfected at home, school and work, especially if used by someone who is ill.41

What is the history of influenza in America and other countries?

The name Influenza originated in 15th century Italy from the belief that the epidemic of respiratory illness was “influenced” by the stars. While the first documented global influenza pandemic appears to have occurred in 1580, ancient Greek literature traces reports of possible influenza as far back as 412 BC.42 43

It is likely that seasonal influenza outbreaks and epidemics have occurred yearly in different parts of the world throughout recorded history. However, because influenza rarely caused significant mortality and morbidity on a global scale, influenza reports in the historical literature likely focused on influenza pandemics and not seasonal outbreaks.

Influenza pandemics occur when a new strain of influenza emerges and has a global impact on human populations because most people - or certain age groups within a population - do not have natural immunity to the new influenza strain. While influenza outbreaks or epidemics typically affect the elderly and those with chronic health issues, influenza pandemics tend to also impact younger people, both healthy individuals and those with chronic illness.44

Between 1700 and the 1918-19 influenza pandemic, historical literature documented at least four influenza pandemics, each occurring between 40 and 60 years apart.45

The 1918-19 influenza pandemic is thought to have originated in the U.S., even though it is often referred to as the “Spanish Flu,” and it was the first flu pandemic of the 20th century. Caused by a type A influenza strain, the 1918-19 pandemic is estimated to have resulted in 20 to 50 million deaths worldwide, including more than 600,000 deaths in the U.S.46 47

The 1957-58 Asian flu pandemic began in February of 1957 in Singapore and continued on to Hong Kong before spreading globally. It is estimated that approximately 1.1 million excess deaths occurred worldwide during this pandemic and there was a noticeable increase in the influenza-related respiratory mortality rate among school aged children and young adults.48 Ten years later, in comparison, the 1968-69 Hong Kong flu pandemic was fairly mild, with 33,800 U.S. deaths being attributed to it.49

In 1976, a type A influenza virus (H1N1/swine flu) was isolated from two soldiers at Fort Dix, New Jersey and approximately 200 more soldiers were subsequently infected. The fear of a repeat of the influenza pandemic of 1918-19 prompted the pre-emptive development of a flu vaccine. The projected swine flu epidemic did not occur and the outbreak was limited to New Jersey, with no additional cases detected after February 1976.50

In April 2009, a new influenza type A H1N1 (swine flu) strain that was first identified and has been confirmed to have originated in Mexico near a pig farm was detected in the United States.51 By April 26, 2009, public health officials from the Centers for Disease Control (CDC) and the U.S. Secretary of Homeland Security declared a national public health emergency.52 The quick declaration of a public health emergency put the production of experimental pandemic H1N1 influenza vaccines on a fast track and vaccine manufacturers were given liability protection, while there was a nationwide promotion for everyone to get vaccinated.53 54 Eventually the CDC recommended that Americans get two flu shots in the 2009-2010 flu season: a seasonal flu shot and a pandemic H1N1 flu shot.55

The 2009 influenza pandemic was mild compared to previous pandemics like the one in 1918-19. The CDC estimated there were more than 60 million cases in the U.S. and 12,469 deaths directly attributable to the 2009 H1N1 “swine flu” virus.56

Can influenza cause injury and/or death?      

The influenza virus is constantly mutating and this frequent change makes it difficult to know exactly which type A and B strains will be circulating during the upcoming flu season.57 58  One particular strain of influenza may be predominant early in a flu season, while another different strain may emerge later in the season.  Timing, severity and duration of the flu season varies widely from year to year, depending the prevalent circulating influenza strains that are associated with mild, moderate or severe illness.59

Official estimates of annual influenza-associated deaths in the United States have varied widely during the last half century.60 61 In the past, the CDC has estimated between 3,000 and 49,000 influenza-related deaths occur every year in the U.S., but the actual number is unknown because influenza-related deaths for persons over age 18 are not required to be reported to the CDC.62 63 64 In 2019, the CDC updated their numbers and estimated that influenza-associated deaths between 2010 and 2018 averaged between a low of 12,000 and a high of 79,000.65 However, the CDC also acknowledged that the actual number of persons in the U.S. who die every year from influenza-related complications is unknown.66

A 2005 article published in the British Medical Journal asked the question: "Are U.S. Flu Death Figures More PR Than Science?"67 The author analyzed the U.S. Vital Statistics Mortality Data, which has been recorded for more than a century by the National Center for Health Statistics, and noted that from 1900 to 2010 the mortality rates for influenza deaths have been dropping and do not closely align with CDC influenza-related mortality estimates.68 Counting death certificates listing influenza as the cause of death could provide more accurate data; however CDC officials maintain this to be a gross underestimation of seasonal influenza’s true impact.” 69 70

The impact of influenza-related illness on people also varies widely. A 2014 study published in The Lancet found that three-quarters of people confirmed with seasonal and pandemic influenza were asymptomatic, meaning they showed no symptoms of illness at all.71 72  People who do not show symptoms of influenza Illness, whether they have been vaccinated or not, can still transmit infection to others.73

For some people who get influenza, however, serious complications develop and can be life-threatening. These complications may include bacterial pneumonia, ear infections, sinus infections, dehydration, sepsis, and worsening of chronic medical conditions, such as congestive heart failure, asthma, or diabetes.74

Who is at highest risk for getting influenza? 

Public health officials state that, while anyone can get sick with influenza, those most at risk for complications are pregnant women, the elderly, individuals with specific chronic medical conditions (i.e., HIV/AIDS, asthma, diabetes, heart or lung diseases), young children under age five, and health care workers.75 76 Due to the fact that influenza viruses are continually changing, the severity of symptoms associated with influenza infections and the prevalence of related complications varies from season to season.77 78

Who is at highest risk for suffering complications from influenza?

The CDC lists the following persons as being at increased risk for complications from influenza: 79

  • Asthma;
  • Neurological and neurodevelopmental conditions including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability (mental retardation), moderate to severe developmental delay, muscular dystrophy, or spinal cord injury;
  • Chronic lung disease (such as chronic obstructive pulmonary disease COPD and cystic fibrosis);
  • Heart disease(such as congenital heart disease, congestive heart failure and coronary artery disease);
  • Blood disorders (such as sickle cell disease);
  • Endocrine disorders (such as diabetesmellitus);
  • Kidney disorders;
  • Liver disorders;
  • Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders);
  • Weakened immune system due to disease or medication (such as people with HIV or AIDS, or cancer, or those on chronic steroids);
  • People younger than 19 years of age who are receiving long-term aspirin therapy;
  • People who are morbidly obese (body mass index more than 40) Calculate Body Mass Index or BMI here.

Can influenza be prevented and are there treatment options?

To decrease the risk of becoming infected with influenza or other viruses, it is important to avoid contact with people who are ill. Frequently washing hands with soap and water or using alcohol-based hand rubs helps to reduce the risk of infection. Covering your nose and mouth with a tissue and properly disposing of it, and keeping surfaces at home, work and school clean can also help to prevent spread of influenza and other types of infections.80

Eating a well-balanced diet, reducing stress, staying properly hydrated and getting enough sleep, Vitamin D and exercise can help reduce the risk of becoming sick.81 82

When you are sick, it is important to stay away from others until they are well to limit your risk of becoming sick, too. The CDC recommends staying home for at least 24 hours after a fever is gone (without the use of medications to reduce fever) except for medical services or other necessary outings.83

Treatments for influenza may include options such as natural home remedies or physician prescribed medications.84 85 86 NVIC encourages all consumers to carefully research the potential risks and benefit of any treatment option being considered in order to make educated decisions.

What is influenza (flu) vaccine? 

There are many different kinds of influenza vaccines available in the U.S. NVIC encourages consumers to read the vaccine manufacturer's package insert information carefully before receiving influenza vaccine or any vaccine.

Standard-Dose Inactivated Flu Vaccine –

  • The most common flu vaccine is the inactivated (killed) influenza vaccine, which is prepared from the fluids of chick embryos inoculated with a specific type(s) of influenza virus. 87 The strains of flu virus in the vaccine are inactivated with formaldehyde and preserved with thimerosal, which is a mercury derivative.88 (There is a limited supply of thimerosal-free or influenza vaccine with trace amounts of thimerosal and it is supplied in single dose vials, which do not require a preservative). This type of inactivated influenza vaccine is administered by injection into the muscle and contains either three (trivalent) or four (quadrivalent) influenza virus type A and type B strains.89 One trivalent flu vaccine, Afluria, is given by jet injector, a medical device which uses high pressure to administer the vaccine.90

High-Dose Trivalent Flu Vaccines -

  • The high-dose trivalent influenza vaccine, Fluzone, is approved for adults age 65 and older and contains four times the amount of antigen than the standard flu vaccine.91 This vaccine is designed to hyper-stimulate the immune system to produce a stronger antibody response in the elderly.92 High-dose Fluzone is the only high-dose trivalent flu vaccine currently available in the U.S.

Recombinant Flu Vaccines -

  • The recombinant flu vaccine, approved for use in 2013, is manufactured through genetic engineering.93 It is produced using insect (armyworm) cells. Flublok is the only recombinant flu vaccine currently licensed in the U.S. and one of two influenza vaccines using alternatives to chicken eggs for production.94 95

Cell-Based Flu Vaccines -

  • Cell-Based flu vaccines differ from standard egg-based flu vaccines because animal cells are used to grow the influenza virus.96 Currently only one cell-based flu vaccine, Flucelvax, is available in the U.S. Licensed in 2012, it is prepared from influenza virus grown in Madin Darby canine kidney cells. This vaccine is approved for use by adults and children age 4 and older.97

Trivalent Flu Vaccine, Adjuvanted -

  • In 2015, the FDA approved Fluad, the first adjuvanted trivalent flu vaccine containing a squalene oil adjuvant (MF59).98 This vaccine was approved for fast track licensure by the FDA, despite limited data on safety and immunogenicity, with approval based on a single clinical trial of about 1,000 healthy adults over the age of 65. 99 This vaccine became available for the first time to adults over the age of 65 for the 2016-2017 flu season.100

Intradermal Flu Vaccine –

  • The intradermal flu vaccine was approved for use in 2012. It is an inactivated injectable influenza vaccine that is injected into the skin instead of the muscle.101 There is one quadrivalent intradermal flu vaccine available, Fluzone Intradermal, and it is licensed for use in adults aged 18 through 64. This vaccine is prepared from influenza viruses propagated in chicken embryos (unhatched baby chicks) and inactivated by formaldehyde. The intradermal flu vaccine does not contain thimerosal.102

Nasal-Spray Flu Vaccine FluMist -

  • A live-virus nasal flu vaccine, FluMist, was licensed by the FDA in June 2003 and initially approved use in healthy people between the ages of 5 and 49.103 It was subsequently approved by the FDA for use in children as young as two years of age but with precautions.104 In 2014, CDC officials recommended FluMist be the influenza vaccine given to children between 2 and 8 years of age but, in 2016, the CDC recommended that FluMist not be given to children or adults of any age because the vaccine had been found to be ineffective.105 In February 2018, however, the CDC approved a new formulation of FluMist as an option for the 2018-2019 flu season despite a lack of vaccine efficacy studies.106 FluMist is prepared by introducing influenza viruses into eggs where they multiply. FluMist is a live virus vaccine and does not contain any preservatives and the vaccine will be available for the 2019/2020 flu season.107

The majority of influenza vaccines were initially designated as Category B or C pharmaceutical products. This means that adequate and well-controlled studies on pregnant women were not conducted prior to licensure of influenza vaccines and it is not known whether the vaccines can cause fetal harm when administered to a pregnant woman or can affect fertility and the reproduction capacity of a woman. 

In 2015, the FDA removed pregnancy categories and replaced it with a Pregnancy and Lactation Labeling Rule.108 This rule affects all influenza vaccine products submitted after June 30, 2015. As new language is phased in, information on risks associated with vaccinating while pregnant will appear in 8.1 of each vaccine’s product insert under Risk Summary. NVIC encourages pregnant women to read this information carefully prior to receiving influenza vaccine or any other vaccine.

Below are links to the U.S. Food & Drug Administration’s (FDA) website for the most current legally-required licensing information published in manufacturer product package inserts for influenza vaccines available in the U.S.  It is important to understand and read this information carefully prior to receiving a vaccine. Vaccine product package inserts contain important information about ingredients, contraindications, precautions, reported adverse reactions, safety and effectiveness data from pre-licensure clinical trials, use recommendations and more.

Quadrivalent Vaccines - Nasal

  • FluMist by MedImmune, LLC

Quadrivalent Vaccines – Injected

  • AFLURIA QUADRIVALENT by Seqirus Pty Ltd.
  • Fluarix Quadrivalent by GlaxoSmithKline Biologicals
  • Flucelvax Quadrivalent by Seqirus, Inc.
  • FluLaval Quadrivalent by ID Biomedical Corporation of Quebec
  • Fluzone by Sanofi Pasteur Inc.

Trivalent Vaccines - Nasal

  • FluMist by MedImmune, LLC

Trivalent Vaccines - Injected

  • AFLURIA by Seqirus Pty Ltd.
  • FluLaval by ID Biomedical Corporation of Quebec
  • Fluarixby GlaxoSmithKline Biologicals
  • FLUAD by Seqirus, Inc.
  • Flublokby Protein Sciences Corporation
  • Flucelvaxby Seqirus, Inc.
  • Fluvirin by Seqirus Vaccines Limited
  • Fluzoneby Sanofi Pasteur, Inc.

What is the history of influenza vaccine use in America?

The 1918-19 influenza pandemic at the beginning of the 20th century stimulated research on the influenza virus and, in 1933, influenza type A was isolated in ferrets. In 1936, influenza type B was isolated and an Australia scientist discovered that the virus could be grown in embryonic hen eggs. These discoveries fueled an interest in the development of an influenza vaccine that would reduce mortality in future epidemics and pandemics.109 110

The first vaccine for influenza was developed in 1938 and given to U.S. soldiers during World War II. A 1944 study of the new influenza vaccine determined that, while helpful in reducing illness with a temperature above 99 degrees F, it did not appear to have an impact on clinical outcomes. In 1947, further evaluation of the influenza vaccine found no difference in health outcomes between those who were vaccinated and those who were not vaccinated.111 112

Early flu vaccines contained only inactivated influenza virus type A (monovalent) but, by 1942, there was a bivalent vaccine containing both influenza type A and influenza type B. This early vaccine caused localized and systemic reactions, especially in children. Despite little evidence of its effectiveness, the influenza vaccine was licensed for use in the U.S. in 1945.113 114 115 116

When the predicted “Asian” flu pandemic materialized in the 1957-1958 flu season, production of a vaccine against this pandemic influenza strain was initiated quickly in hopes it would limit mortality and reduce severity of the illness for vaccinated persons. Approximately 40 million doses of the vaccine were administered to people in the U.S.

However, due to the lack of effectiveness and limited availability, public health officials reported that “the vaccine had no appreciable effect on the trend of the pandemic.”117 The failure was presumed to be primarily related to the lack of availability of the vaccine and, by 1960, health officials started recommending routine flu shots every year for the elderly and certain high risk groups. 118

A review of this “annual flu shot” recommendation four years later found little evidence that annual vaccination of seniors and others thought to be at high risk for influenza had any appreciable impact on influenza-related mortality rates. A 1968 double-blind randomized study conducted by CDC officials and published by the World Health Organization (WHO) came to similar conclusions and even suggested that “attention should be redirected towards finding a more efficacious means of protection.”119 Yet, despite studies demonstrating that the influenza vaccine was ineffective, government vaccine policy recommendations for annual flu shots continued.

In early 1976, two cases of H1N1 “swine flu” were confirmed in the U.S. and public health officials working with the pharmaceutical industry made the decision to start manufacturing a vaccine out of concerns that this new strain of type A influenza could start a pandemic similar to the 1918-19 influenza pandemic. The U.S. Congress approved $137 million dollars for vaccine production with the goal that nearly all Americans would be vaccinated before the flu season started.120 

Mass production of the swine flu vaccine did not start until the U.S. Congress gave in to demands from drug companies lobbying for a product liability shield to block vaccine injury lawsuits for any harm caused by swine flu shots.121 This decision called into question the safety of the swine flu vaccine and public support for the mass vaccination program began to wane.

The swine flu vaccination program began in October 1976 and, within two weeks public concerns about safety were highlighted when three senior citizens died after getting vaccinated at the same clinic. By December 1976, there had been numerous reports of people becoming paralyzed from Guillain-Barre Syndrome (GBS) which developed after getting swine flu shots and, with no evidence of an impending influenza pandemic, the swine flu vaccination program was cancelled.122

Despite this setback, seasonal flu vaccine production continued and, in 1978, the first trivalent influenza vaccine was licensed for use in the U.S. after scientists identified two different influenza A strains circulating simultaneously. The new inactivated trivalent influenza vaccine contained two strains of influenza A and one strain of influenza B virus.123

The first live attenuated influenza vaccine (LAIV), FluMist, was approved by the FDA in 2003. A trivalent vaccine administered as a nasal spray, FluMist was approved for use in healthy children and adults between 5 and 49 years of age.124 This live virus flu vaccine was not recommended for individuals with a history of asthma or other respiratory illness, any underlying chronic illness, including those with immune or metabolic dysfunction, persons with a history of GBS, children or adolescents on aspirin therapy, pregnant women, or anyone with an egg allergy. 

Importantly, FluMist was not recommended for people coming in close contact with immunocompromised individuals “because of the theoretical risk that a live, attenuated vaccine virus could be transmitted to the immunosuppressed person and cause disease.”125 There are documented cases in the medical literature of vaccine virus infection, shedding and transmission with FluMist and other live attenuated virus vaccines.126 127

On April 26, 2009, public health officials declared a national public health emergency after the discovery of a new Influenza A (H1N1) strain was first identified in Mexico and then in the U.S.128 A new pandemic H1N1 swine flu vaccine was quickly licensed and made available to the public in October of 2009, but a 2011 study of the effectiveness of the 2009 pandemic H1N1 swine flu vaccine found it had an overall effectiveness of only 56 percent.129

The influenza vaccine market has grown considerably since 2009 with the introduction of several new types of influenza vaccines along with new delivery methods, including vaccines that use insect and animal cells for production instead of chicken eggs.

A “high-dose” influenza vaccine targeting those over age 65 years was approved by the FDA in 2009 and became available in the U.S. for the 2010-2011 flu season.130 This vaccine contains four times the amount of antigen as other flu vaccines and is supposed to stimulate a stronger immune response that will produce more antibodies and, theoretically, give the elderly better protection from getting sick with influenza.131

In 2012, the FDA approved the first quadrivalent influenza vaccine, containing two type A and two type B influenza viruses.132 FluMist Quadrivalent, the live attenuated influenza vaccine, became available for the 2013-2014 flu season, and several quadrivalent inactivated injectable vaccines followed soon afterward. Quadrivalent vaccines add another strain of type B influenza virus to the traditional trivalent vaccines, which contain two strains of type A influenza virus and one strain of type B influenza virus, with the goal of improving flu vaccine effectiveness.

The first cell-based influenza vaccine, Flucelvax, was approved by the FDA in 2012, using canine (dog) kidney cells133 instead of chicken embryos to produce the vaccine.134 In 2013, Flublok, a recombinant influenza vaccine using armyworm caterpillar cells instead of chicken embryos for production, was approved for use in adults 18 to 49 years of age.135 136 137 Flublok quadrivalent received FDA approval for use in adults 18 and older in July of 2016.138

On June 26, 2014, the CDC recommended giving FluMist to healthy children between 2 and 8 years of age instead of inactivated injectable influenza vaccines but, 2 years later, in June 2016, the CDC withdrew its recommendation based on data which determined that the vaccine was completely ineffective in preventing influenza.139 140 On February 21, 2018, the CDC reinstated a new formulation of FluMist in advance of the 2018-2019 flu season. Vaccine efficacy studies on this new formulation of FluMist have not been completed, therefore it is unknown whether the vaccine offers any protection from influenza. The CDC voted against recommending FluMist over the available inactivated injectable influenza vaccines but stated it could be considered as an option, if appropriate.141

In 2015, the FDA approved FLUAD, a trivalent influenza vaccine containing MF 59, a squalene oil adjuvant that hyper-stimulates the immune system to produce more antibodies, for use in adults 65 and older.142 The licensing of FLUAD was fast-tracked by the FDA despite concerns over the use of the squalene adjuvant and its association with immune and neurological disorders.143

In addition to an increase in the types of available influenza vaccines, manufacturers have also added new delivery methods. In 2012, the first intradermal influenza vaccine (administered between skin layers rather than into the muscle) was approved for use.144 In 2014, the first jet injector (vaccine delivery device using high-pressure) to administer influenza vaccine became available.145

As the influenza vaccine market expanded, so did recommendations for use by the CDC’s Advisory Committee on Immunization Practices (ACIP).

In 1984, the CDC recommended annual flu shots for high risk individuals, which included adults over the age of 65; any person with a chronic illness or a metabolic disorder; persons living in nursing homes or other long term care facilities; and health care personnel. At that time, pregnancy was not considered to be a high risk factor for severe illness or complications from influenza. The 1984 ACIP committee stated, “Pregnancy has not been demonstrated to be a risk factor for severe influenza infection, except in the largest pandemics of 1918-1919 and 1957-1958.”146

However, in 1997, the CDC updated influenza vaccine recommendations to include pregnant women in their second or third trimester. This recommendation was considered an off-label use of the vaccine because the FDA had not licensed influenza vaccine for use by pregnant women.147 The CDC’s recommendation in 1997 was based on information contained in a small number of documents from the 1918-1919 and 1957-1958 influenza pandemics, and a few case reports and small studies which reported an increase in influenza-related hospitalizations in pregnant women.148

Between 1999 and 2010, the ACIP annual recommendations for the seasonal flu vaccine quickly expanded to include more and more target populations. Infants and children, aged 6 months to 23 months, were added in 2004.149 The presence of thimerosal, a mercury-containing preservative present in all multi-vial flu vaccine vials, was discussed by ACIP due to a 1999 recommendation which called for its removal from all vaccines routinely administered to children.150 In 2004, however, the CDC stated that, “the benefits of influenza vaccination outweigh the theoretical risk, if any, for thimerosal exposure through vaccination,” and there was no recommendation made for infants, children or even pregnant women to receive a thimerosal-free influenza vaccine.151

By 2010, ACIP voted to recommend that every person six months and older, including pregnant women at any stage of pregnancy, receive an annual flu shot. The only contraindications were for persons with a history of hypersensitivity or anaphylaxis to eggs or any other influenza vaccine ingredient, or history of Guillain-Barre Syndrome (GBS).152

In 2011, however, the CDC began recommending that individuals who had previously developed hives following exposure to eggs receive the influenza vaccine 153 and by 2016, egg allergies were no longer considered a contraindication to receiving a flu vaccine.154

Currently a severe allergy to a vaccine component or history of a life threatening allergic reaction to a previous flu shot are the only CDC approved official contraindications (medical reasons for not getting vaccinated) to receiving influenza vaccine.  A history of GBS within 6 weeks of a previous flu vaccine, a severe egg allergy (i.e. respiratory distress, recurrent vomiting, angioedema, lightheadedness,  treatment with epinephrine) or “moderate or severe acute illness with or without a fever,” are now only considered precautions to vaccination. According to the CDC, vaccination should be deferred in the presence of a precaution, but persons may receive the vaccine if the benefit of vaccination is believed to outweigh the risk.155

Despite the ever-growing number of influenza vaccines available in the U.S. market, the effectiveness of influenza vaccines has not improved very much over the years. In 2003-2004, the CDC increased research efforts to determine just how well seasonal flu vaccine works in preventing cases of influenza in vaccinated persons.

Since 2004, the seasonal influenza vaccine has failed to prevent influenza in vaccinated persons more than half the time, demonstrating a low of 10 percent effectiveness in 2004/2005 to a high of 60 percent effectiveness in 2010/2011. The average effectiveness of influenza vaccines over the past 14 flu seasons has been less than 41 percent.156

The Cochrane Collaboration’s 2014 review of the medical literature on influenza vaccine noted bias in the publication of influenza vaccine research on effectiveness and safety:

“An earlier review of 274 influenza vaccine studies in all age groups (including most of the studies in this review) showed an inverse relationship between risk of bias and the direction of study conclusions. Conclusions favourable to the use of influenza vaccines were associated with a higher risk of bias. In these studies, the authors made claims and drew conclusions that were unsupported by the data they presented. In addition, industry-funded studies are more likely to have favourable conclusions, to be published in significantly higher-impact factor journals and to have higher citation rates than non-industry-funded studies. This difference is not explained by either their size or methodological quality (Jefferson 2009a). Any interpretation of the body of evidence in this review should be made with these findings in mind.”157

The Cochrane review also concluded that recommendations for routine use of influenza vaccine as a routine public health measure was not supported by the published evidence base and stated,

The results of this review provide no evidence for the utilisation of vaccination against influenza in healthy adults as a routine public health measure. As healthy adults have a low risk of complications due to respiratory disease, the use of the vaccine may only be advised as an individual protective measure.” 158

The 2018 Cochrane review of influenza vaccination in healthy adults found that the flu vaccine may only have a modest impact on reducing the number of cases of influenza and influenza-like illness but the data was insufficient to determine whether vaccination had any impact on working days lost or on reducing serious complications of the flu during influenza season.159

How effective is influenza vaccine?

Like all vaccines, the influenza vaccine only gives a temporary artificial immunity and, in the case of flu shots, that temporary artificial immunity is confined to the influenza virus strains contained in the vaccine. The only way to get more complete and longer lasting immunity to a strain of type A or B influenza is to recover from the illness. Natural immunity to a particular strain of influenza can be protective against severe illness symptoms if that strain or a closely related strain circulates in the future.

The flu vaccine, however, only provides temporary immunity to selected type A and B strains and those strains may or may not be prevalent each year. Since 2010, U.S. public health officials have directed doctors to give every American over six months old a flu shot every year, whether or not they are healthy or at high risk for influenza complications.160 161

Every year, public health officials at the World Health Organization (WHO) and U.S. Centers for Disease Control and Prevention (CDC) try to guess which three or four influenza strains are most likely to be circulating and causing illness in the U.S. the following year to determine which strains will be included in vaccine manufactured for the upcoming flu season. Despite elaborate influenza monitoring systems by the WHO and U.S.162 and scientists worldwide to select the strains to be targeted in the following year’s flu vaccine, studies by the U.S. Flu Vaccine Effectiveness Network have shown that, since the 2004/2005 flu season, the vaccine has never been more than 60 percent effective.163

A 2005 study on the impact of flu vaccination on mortality in adults 65 years of age and older determined that an increase in flu vaccine coverage after 1980 in senior adults had no impact on reducing mortality rates in any age group.164

Between the 2004/2005 and 2017/2018 flu seasons, the influenza vaccine was reported to be less than 50 percent effective in 10 out of 14 flu seasons. In the 2014-2015 flu season, the influenza vaccine was only 19 percent effective.165 A 2011 review of existing research determined that the inactivated influenza vaccine had a pooled efficacy of 59 percent for adults 18 to 65 years of age for 8 out of 12 seasons. Similar data for inactivated influenza vaccine for adults over 65 years of age and children between 2 and 17 years of age was reported to be lacking. This same review found that live-attenuated influenza vaccine (LAIV), had a pooled efficacy of 83 percent in 9 of the 12 seasons analyzed for children aged six months to seven years. Similar data for LAIV efficacy for children aged 8 to 17 years was lacking and requires additional study.166 

A Canadian study published in 2015 found that the effectiveness of the flu vaccine decreased when a person received the shot two years in a row. Because of these negative findings which implied that the vaccine increased a person’s susceptibility to influenza, study authors recommended further research be completed. 167 168

In 2016, CDC officials advised against use of the live attenuated nasal influenza vaccine based on effectiveness data collected between 2013 and 2016 which showed LAIV vaccine to be only 3 percent effective against any influenza virus among children 2 to 17 years of age.169 However, in February 2018, CDC officials voted to approve that a new formulation of LAIV be added as an option, when appropriate, for the 2018-2019 flu season. Vaccine efficacy studies on whether this new formulation of FluMist have not been completed and this approval was based on data analysis provided by the manufacturer.170 FluMist will remain available for use during the 2019/2020 flu season.171

In the fall of 2017, scientists reported that the H3N2 influenza virus strain mutated during the 2014-2015 season and, although the 2016-2017 seasonal flu vaccine was updated to include the mutated strain, another mutation occurred that season in manufacturing labs when the H3N2 strain was grown in chicken eggs to produce the vaccine. There is emerging evidence that H3N2 influenza viruses cannot be grown in chicken eggs without adaptive mutations occurring.172 The 2017/2018 influenza vaccine reportedly was only 10 percent effective in the southern hemisphere because the mutated H3N2 strain was the one making most people sick, but it was not included the vaccine.173

In 2018, the Cochrane Collaboration published a review of medical literature on the effects of the influenza vaccination in the elderly and concluded that:

“The available evidence relating to complications is of poor quality, insufficient, or old and provides no clear guidance for public health regarding the safety, efficacy, or effectiveness of influenza vaccines for people aged 65 years or older.”174

The Cochrane Collaboration’s 2014 review of the medical literature on influenza vaccine had previously noted bias in the publication of influenza vaccine research on effectiveness and safety and reported that:

“An earlier review of 274 influenza vaccine studies in all age groups (including most of the studies in this review) showed an inverse relationship between risk of bias and the direction of study conclusions. Conclusions favourable to the use of influenza vaccines were associated with a higher risk of bias. In these studies, the authors made claims and drew conclusions that were unsupported by the data they presented. In addition, industry-funded studies are more likely to have favourable conclusions, to be published in significantly higher-impact factor journals and to have higher citation rates than non-industry-funded studies. This difference is not explained by either their size or methodological quality (Jefferson 2009a). Any interpretation of the body of evidence in this review should be made with these findings in mind.” 175

This 2014 Cochrane review also concluded that recommendations for routine use of influenza vaccine as a routine public health measure was not supported by the published evidence base and stated:

The results of this review provide no evidence for the utilisation of vaccination against influenza in healthy adults as a routine public health measure. As healthy adults have a low risk of complications due to respiratory disease, the use of the vaccine may only be advised as an individual protective measure.” 176

The 2018 Cochrane review of influenza vaccination in healthy adults found that the flu vaccine may only have a modest impact on reducing the number of cases of influenza and influenza-like illness, but the data was insufficient to determine whether vaccination had any impact on working days lost or on reducing serious complications of the flu during influenza season.177

In June 2019, the CDC reported that the 2018-2019 seasonal flu vaccine offered no protection against the circulating H3N2 flu strain which emerged in late February and overall flu vaccine effectiveness was reported at only 29 percent. Among adults hospitalized for the flu, the vaccine’s effectiveness against the H3N2 strain was reported at -43 percent. A negative percentage indicates that persons who were vaccinated with the 2018-2019 seasonal flu vaccine were more likely to be hospitalized for flu, than those who were not. 178

Can influenza vaccine cause injury and death?

The Institute of Medicine (IOM) has acknowledged that there is individual susceptibility to vaccine reactions for genetic, biological and environmental reasons, but that vaccine providers cannot accurately predict prior to a vaccine’s administration who will suffer complications, injury or death from vaccination.179 However, a person who has previously had a serious reaction to a vaccination or is acutely or chronically ill should become informed about all potential risks associated with vaccination and discuss any concerns with a trusted health care professional before receiving an influenza vaccine or any other vaccine.

The most common reported reactions following administration of the inactivated influenza vaccine include headache, muscle ache, fever, and pain, swelling and redness at the injection site.

Children who receive the influenza vaccine at the same time as the DTaP (diphtheria, tetanus, acellular pertussis) and/or pneumococcal (PCV13) are at a higher risk of suffering from a seizure induced by fever.180

One of the most serious documented influenza vaccine reactions is Guillain-Barre Syndrome (GBS). 181  An immune mediated painful and disabling neurological disorder that can occur after viral infection or vaccination, GBS involves inflammation of the peripheral nervous system and can cause temporary or permanent paralysis that may lead to death. 182 GBS usually develops within two to four weeks of vaccination.

Characterized by muscle weakness, unsteady gait, numbness, tingling, pain, GBS can cause paralysis of the face or one or more limbs. It can take several months for recovery or it can leave the affected person with chronic health problems and disability.183 The mortality rate with GBS is highest among the elderly and those who develop severe complications.184

The CDC states that:

“Some studies have found a possible small association of injectable flu vaccine with Guillain-Barré syndrome (GBS). Overall, these studies estimated the risk for GBS after vaccination as fewer than 1 or 2 cases of GBS per one million people vaccinated. Other studies have not found any association. GBS also, rarely, occurs after flu illness. Even though GBS following flu illness is rare, GBS is more common following flu illness than following flu vaccination. GBS has not been associated with the nasal spray vaccine.” 185

In the comprehensive report evaluating scientific evidence, Adverse Effects of Vaccines: Evidence and Causality, 186 published in 2012 by the Institute of Medicine (IOM), 27 reported vaccine adverse events following the influenza vaccine were evaluated by a physician committee.187 These adverse events included GBS, stroke, myocardial infarction, Chronic Inflammatory Disseminated Polyneuropathy, Acute Disseminated Encephalomyelitis (ADEM), optic neuritis, Bell’s palsy, encephalopathy, encephalitis, and more.

The IOM committee concluded that in only 1 out of the 27 influenza vaccine-related adverse events – anaphylaxis - the scientific evidence convincingly supported a causal relationship between the vaccine and the adverse event. The committee also concluded that it favored acceptance of an association between the flu vaccine and Oculorespiratory Syndrome, a syndrome which generally occurs between 2- and 24-hours following vaccine administration and is characterized by symptoms which include acute respiratory symptoms (including respiratory distress, throat tightness and/or chest discomfort), red eyes, and facial swelling. After primarily examining epidemiologic studies, the committee members favored rejection of an association between 2 vaccine-related adverse events -Bell’s Palsy and asthma exacerbation or reactive airway disease episodes in children and adults- and the influenza vaccine. For the remaining 23 reported vaccine adverse events, including GBS, the IOM committee concluded that there was inadequate evidence to support or reject a causal relationship between the influenza virus vaccine and the reported adverse event, primarily because there was either an absence of methodologically sound published studies or too few quality studies to make a determination.188

The U.S. government, however, recognized GBS occurring between 3 and 42 days following the influenza vaccine as a vaccine injury and in 2017, GBS was added to the National Vaccine Injury Compensation Program’s Vaccine Injury Table.

Adult influenza vaccine injury claims are now the leading claim submitted to the federal Vaccine Injury Compensation Program (VICP), with GBS as the leading alleged injury.189 190

Additional influenza vaccine injuries recognized by the U.S. government and included in the Vaccine Injury Table include anaphylaxis within 4 hours of vaccination, vasovagal syncope within 1 hour of vaccination, and shoulder injury related to vaccine administration (SIRVA) within 48 hours of vaccination. SIRVA is a recognized injury resulting from the administration of the vaccine antigen or needle into or around the bursa of the shoulder. SIRVA causes an inflammatory response and manifests as pain and reduced mobility to the shoulder in which the vaccine was administered.191

Published studies have linked the influenza vaccine to numerous serious adverse events including Acute Disseminated Encephalomyelitis (ADEM), 192 193 194 195 196 197 198 199 200 201 stroke,202 brachial neuritis,203204 encephalopathy,205 arthritis,206 bullous pemphigoid,207 208 209 210 211 212 213 vasculitis,214 215 216 217, myocardial infarction,218 transverse myelitis,219 220 221 222 223 optic neuritis,224 225 Bell’s Palsy,226 and more. 227

A Canadian study published in 2015 found that the effectiveness of the flu vaccine decreased when a person received the shot two years in a row. Because of these negative findings which implied that the vaccine increased a person’s susceptibility to influenza, study authors recommended further research be completed. 228 229

In 2017, a Centers for Disease Control (CDC) funded study reported that women vaccinated in the early part of their pregnancy with a flu vaccine containing the pandemic H1N1 (H1N1pdm09) strain and who also had been previously vaccinated the prior season with a H1N1pdm09-containing flu vaccine had a greater risk of miscarriage in the first four weeks following vaccination. The CDC conducted further research among women who were pregnant during the 2012-2013 through 2014-2015 flu seasons and eligible to receive the flu vaccine. This study, which contradicted their previous findings, reported that the influenza vaccine did not cause miscarriages in the women evaluated in the study.230 231

As of July 31, 2019, there have been more than 166,178 reports of influenza vaccine reactions, hospitalizations, injuries and deaths following influenza vaccinations made to the federal Vaccine Adverse Events Reporting System (VAERS), including 1,673 related deaths, 13,373 hospitalizations, and 3,358 related disabilities. However, the numbers of vaccine-related injuries and deaths reported to VAERS may not reflect the true number of serious health problems that occur after influenza vaccination.

Even though the National Childhood Vaccine Injury Act of 1986 legally required pediatricians and other vaccine providers to report serious health problems following vaccination to federal health agencies (VAERS), many doctors and other medical workers giving vaccines to children and adults fail to report vaccine-related health problem to VAERS. There is evidence that only between 1 and 10 percent of serious health problems that occur after use of prescription drugs or vaccines in the U.S. are ever reported to federal health officials who are responsible for regulating the safety of drugs and vaccines and issue national vaccine policy recommendations.232 233 234 235 236

As of Sept 1, 2019, there have been 5,560 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following influenza vaccination, including 174 deaths and 5,386 serious injuries. Of that number, the U.S. Court of Claims administering the VICP has compensated 3,129 children and adults, who have filed claims for influenza vaccine injury.237

Who is at highest risk for complications from influenza vaccine?

The Institute of Medicine (IOM) has acknowledged that there is individual susceptibility to vaccine reactions for genetic, biological and environmental reasons but that vaccine providers cannot accurately predict prior to a vaccine’s administration who will suffer complications, injury or death from vaccination. 238 However, a person who has previously had a serious reaction to a vaccination or is acutely or chronically ill should become informed about all potential risks associated with vaccination and discuss any concerns with a trusted health care professional before receiving influenza vaccine or any other vaccine.

Currently a severe allergy to a vaccine component or history of a life-threatening allergic reaction to a previous flu shot are the only CDC approved official contraindications (medical reasons for not getting vaccinated) to receiving influenza vaccine.  A history of GBS within 6 weeks of a previous flu vaccine, a severe egg allergy (i.e. respiratory distress, recurrent vomiting, angioedema, lightheadedness, treatment with epinephrine) or “moderate or severe acute illness with or without a fever,” are now only considered precautions to vaccination. According to the CDC, vaccination should be deferred in the presence of a precaution, but persons may receive the vaccine if the benefit of vaccination is believed to outweigh the risk.239

Who should not get the Influenza (flu) vaccines?

Different influenza vaccines are licensed by the FDA and approved for use in different groups of people according to a person’s age, state of health and personal history of allergies or reactions to previous vaccinations. By federal law, pharmaceutical companies producing vaccines for release in the US. must publish information that accompanies vials of vaccine shipped to public health clinics and doctors’ offices that contain information about the vaccine’s ingredients, safety and effectiveness data from pre-licensure clinical trials, contraindications and precautions, reported vaccine adverse events, age use recommendations and more.

Prior to receiving an influenza vaccination or any vaccination, NVIC encourages consumers to read information contained in the vaccine manufacturer package insert carefully.

Note: There are certain influenza vaccines that are licensed for use by people in certain   age groups. For example, high-dose flu shots are not licensed for use by people under age 65 years and flu shots administered intradermally are not licensed for use by children under age 18 years. Refer to the specific vaccine’s product insert in Influenza Quick Facts for additional information.

According to most manufacturers’ package inserts for influenza vaccines, children younger than six months of age and people with severe, life-threatening allergies to influenza vaccine or any ingredient in the vaccine should not receive flu shots.

Most influenza vaccine package inserts with the exception of Flucelvax,240 using Madin Darby canine kidney cells for production, and Flublok,241 using armyworm cells for production, list an allergy to egg and egg protein as a contraindication to vaccination because most influenza vaccines are made using chicken eggs. Flublok, however, is the only flu vaccine considered completely egg-free.242

In 2016, the CDC’s Advisory Committee on Immunization Practices (ACIP) revised flu shot recommendations for people with egg allergies and stated that individuals with an allergy to egg can receive any type of flu vaccine, whether manufacturers use chicken eggs for production or not. 243

CDC officials state that individuals who develop hives from egg products may be vaccinated without any special precautions, while those who have experienced a severe anaphylactic reaction (one involving respiratory distress, angioedema or use of epinephrine) should be monitored in a setting where there is a health care professional trained to recognize and quickly treat an anaphylactic reaction. While CDC officials state that allergic reactions can occur in individuals who are allergic to eggs, they consider the reaction rare and not serious enough to warrant a contraindication. 244

Currently a severe allergy to a vaccine component or a history of a life-threatening allergic reaction to a previous flu shot are the only CDC approved official contraindications (medical reasons for not getting vaccinated) to receiving influenza vaccine.  A history of GBS within 6 weeks of a previous flu vaccine, a severe egg allergy (i.e. respiratory distress, recurrent vomiting, angioedema, lightheadedness,  treatment with epinephrine) or “moderate or severe acute illness with or without a fever,” are now only considered  precautions to vaccination. According to the CDC, vaccination should be deferred in the presence of a precaution, but persons may receive the vaccine if the benefit of vaccination is believed to outweigh the risk.245

Live Nasal Spray Flu Vaccine (FluMist): FluMist is a live virus vaccine and a vaccinated person may potentially shed and transmit the live vaccine strain influenza virus to others.246 247 In 2016, the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended against the use of this vaccine when it was found to be ineffective at preventing influenza. 248 It was, however, approved as an option again for the 2018/2019 flu season without evidence to support that a revised formulation would offer any protection. 249 FluMist will be available for use during the 2019/2020 season.

  • Individuals who should not get a live nasal spray influenza vaccine or who should speak with their health care provider prior to vaccination include:250
    • Children younger than two years old
    • Adults 50 years and older
    • Persons with a history of a severe allergic reaction to any component of the vaccine or to a previous dose of any influenza vaccine
    • People who are allergic to eggs
    • Children 2  through 17 years of age who are receiving aspirin or undergoing aspirin-containing therapy
    • Pregnant women
    • History of Guillain-Barre Syndrome (GBS) within 6 weeks of a previous dose of influenza vaccine
    • People with weakened immune systems (immunosuppression)
    • Children two to four years of age who have asthma or have had a history of wheezing in the past 12 months
    • People who have taken influenza antiviral drugs within the previous 48 hours
    • Persons 5 and older with asthma
    • People who care for severely immunocompromised persons who require a protective environment
    • Individuals with medical conditions which may put them at higher risk of serious flu complications (i.e., kidney, heart, or lung disease, kidney or liver disorders, metabolic or neuromuscular or neurologic disorders)
    • People who are moderately or severely ill.

 Is flu vaccine recommended for children? 

One consideration with the recommended widespread administration of annual flu shots to all children over six months of age is interference with the acquisition of influenza antibodies acquired after recovery from type A or B influenza infections. The question of whether it is better for healthy children, who rarely suffer complications from flu, to get the flu and develop permanent immunity to that flu strain or whether it is better for children to get vaccinated every year to try to suppress all flu infection in early childhood is a question that has yet to be adequately answered by medical science.

Although in the past the flu vaccine has not been recommended for healthy children, today vaccination of children between the ages of 6 months and 18 years is strongly recommended by the Advisory Committee on Immunization Practices (ACIP) of the CDC251 and New Jersey, Ohio, Connecticut, New York City, and Rhode Island require influenza vaccine for daycare and/ or preschool entry.252

Is influenza vaccine safe during pregnancy?

In years past, pregnancy was also a contraindication to flu vaccine but, today, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control (CDC) recommends flu vaccine for all pregnant women.253

Initially, most Influenza vaccines were classified as Category B or C drugs, which means that adequate and well-controlled studies on pregnant women have not been conducted and it is not known whether these vaccines can cause fetal harm when administered to a pregnant woman or if they can affect reproduction capacity.254 

In 2015, the FDA removed pregnancy categories due to concerns of confusion and oversimplification and replaced it with the Pregnancy and Lactation Labeling Rule.255 This rule affects all influenza vaccine products submitted for approval after June 30, 2015. As new language is phased in, information on risks associated with vaccinating while pregnant will appear in 8.1 of each vaccine’s product insert under Risk Summary. NVIC encourages consumers read this information carefully prior to receiving a vaccine.

Prior to the FDA licensing of all influenza vaccines, drug companies did not test the safety and effectiveness in pregnant women256 and little data is available on biological responses to these vaccines that could affect pregnancy and birth outcomes.257

Pregnant women should also be aware that the multi-dose flu vaccine contains Thimerosal, which is a mercury derivative. Mercury is toxic to the brain and has been found to be associated with brain damage and developmental delays in babies whose mothers were exposed to high levels of mercury during pregnancy.258 259

In December 2016, Congress signed the 21st Century Cures Act into law. This new law protects vaccine manufacturers from lawsuits in civil court if an FDA licensed vaccine given to a pregnant woman causes the injury or death of her unborn child in the womb.260 261 As a result, policies relating to compensating vaccine injuries sustained by an unborn child in the womb are being developed.

In 2017, a Centers for Disease Control (CDC) funded study reported that women vaccinated in the early part of their pregnancy with a flu vaccine containing the pandemic H1N1 (H1N1pdm09) strain and who also had been previously vaccinated the prior season with a  H1N1pdm09-containing flu vaccine had a greater risk of miscarriage in the first four weeks following vaccination. The CDC conducted further research among women who were pregnant during the 2012-2013 through 2014-2015 flu seasons and eligible to receive the flu vaccine. This study, which contradicted their previous findings, reported that the influenza vaccine did not cause miscarriages in the women evaluated in the study.262 263

What about mercury in the influenza vaccine?

In 1999, the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA)264 directed the vaccine manufacturers to take mercury out of all childhood vaccines.

In October 2001, the Institute of Medicine issued a report that said it is "biologically plausible" that mercury-containing vaccines could cause injury to the brain but there have been “too few scientific studies conducted to prove conclusively that mercury in vaccines has caused brain damage.”265

Nevertheless, the Institute of Medicine recommended that drug companies take all mercury out of all vaccines and over-the-counter drugs.

In compliance with this recommendation a preservative-free flu vaccine formulated for children ages 6 to 35 months, with only a trace amount of thimerosal, is available in a limited amount. It is distinguished by a pink syringe plunger rod in the pre-filled syringe or in a single dose vial.  All multi-dose vials of influenza vaccine contain thimerosal.

Many influenza vaccines in the U.S. also contain the mercury preservative, Thimerosal, in amounts above federal safety guidelines. Thimerosal free influenza vaccine is also licensed in the U.S. and it is advisable to request these vaccines in advance from your healthcare provider, if your preference is the Thimerosal free version. Click here to determine which vaccines are thimerosal free.

What questions should I ask my doctor about the influenza vaccine?

NVIC’s If You Vaccinate, Ask 8! webpage downloadable brochure suggests asking eight questions before you make a vaccination decision for yourself, or for your child. If you review these questions before your appointment, you will be better prepared to ask your doctor questions.  Also make sure that the nurse or doctor gives you the relevant Vaccine Information Statement (VIS) for the vaccine or vaccines you are considering well ahead of time to allow you to review it before you or your child gets vaccinated. Copies of VIS for each vaccine are also available on the CDC's website and there is a link to the VIS for influenza vaccine on NVIC's “Quick Facts” at the top of this page. 

Due to the brevity of the VIS, it is also a good idea to read the vaccine manufacturer product insert that can be obtained from NVIC’s Influenza Quick Facts above, doctor or public health clinic to get additional information.  Federal law requires drug companies marketing vaccines to include certain kinds of vaccine benefit, risk and use information in product information inserts that may not be available in other published information, like the VIS.  

Other questions that may be useful to discuss with your doctor before getting the influenza vaccine are: 

  • If other vaccines in addition to influenza vaccine are scheduled for my child at this office visit, am I allowed to modify the schedule so fewer vaccines are given at once?
  • What should I do if my child has a high fever or appears very ill after vaccination?
  • What other kinds of reaction symptoms should I call to report after influenza vaccination?
  • If the influenza vaccine doesn’t protect my child, do I have any other options for preventing influenza infection?

It also is important to be able to recognize a vaccine reaction and seek immediate medical attention if the reaction appears serious, as well as know how to make a vaccine reaction report to federal health officials at the Vaccine Adverse Reporting System (VAERS). NVIC’s Report  Vaccine Reactions—It’s the Law webpage can help you file a vaccine reaction report yourself to VAERS if your doctor fails or refuses to make a report.

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References

1 CDC Understanding Influenza Viruses. July 10, 2019

2 CDC Pandemic Influenza. Jan. 24, 2019

3 CDC Flu Symptoms & Complications. Sept. 5, 2019

4 CDC Update: Influenza Activity in the United States During the 2018–19 Season and Composition of the 2019–20 Influenza Vaccine MMWR June 21, 2019; 68(24);544–551

5 CDC Influenza Viruses Isolated by WHO/NREVSS Collaborating Laboratories 2018-2019 Season

6 CDC How Flu Spreads. Aug. 27, 2018

7 CDC Personal NPIs: Everyday Preventive Actions Aug. 26, 2019

8 Mercola.com How to Prevent the Flu -- as Easy as 1, 2, 3... Dec. 9, 2009

9 Urashima M, Segawa T et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren Am J Clin Nutr May 2010; 91(5):1255-1260.

10 CDC Nonpharmaceutical Interventions (NPIs) – At Home. Aug. 26, 2019

11 CDC Different Types of Flu Vaccines. Sept. 4, 2019

12 CDC Selecting Viruses for the Seasonal Influenza Vaccine. Sept. 4, 2018

13 CDC How Influenza (Flu) Vaccines Are Made. Sept. 24, 2018

14 CDC Thimerosal in Flu Vaccine Oct.16, 2015

15 CDC Update: ACIP Recommendations for the Use of Quadrivalent Live Attenuated Influenza Vaccine (LAIV4) — United States, 2018–19 Influenza Season MMWR June 8, 2018; 67(22);643–645

16 Walker M. ACIP Reinstates FluMist for 2018-2019 Flu Season. MEDPAGE TODAY Feb. 21, 2018

17 CDC Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2019–20 Influenza Season MMWR Aug. 23, 2019. 68(3);1–21

18 CDC Influenza – Flu symptoms & Complications. Sept. 5, 2019

19 CDC Key Facts About Influenza (Flu) Sept. 13, 2019

20 World Health Organization Influenza June 19, 2019

21 CDC Influenza A Subtypes and the Species Affected Sept. 27, 2018

22 CDC How the Flu Virus Can Change: “Drift” and “Shift”  Sept. 27, 2017

23 CDC Types of Influenza Viruses. Sept. 27, 2017.

24  Nordqvist C. Everything you need to know about pandemics. Medical News Today May 22, 2018.

25 Taubenberger JK, Morens DM. 1918 Influenza: The Mother of All Pandemics. Emerg Infect Dis 2006; 12(1): 16-22.

26 CDC Update: Influenza Activity in the United States During the 2018–19 Season and Composition of the 2019–20 Influenza Vaccine MMWR June 21, 2019; 68(24);544–551

27 CDC Influenza Viruses Isolated by WHO/NREVSS Collaborating Laboratories 2018-2019 Season

28 CDC Influenza - Flu Symptoms & Complications Sept. 5, 2019

29 CDC Estimates of Deaths Associated with Seasonal Influenza --- United States, 1976—2007 MMWR Aug. 27, 2010; 59(33);1057-1062.

30 CDC Disease Burden of Influenza. Feb. 19, 2019

31 CDC Frequently Asked Questions about Estimated Flu Burden Nov. 5, 2018

32 CDC Clinical Signs and Symptoms of Influenza. Mar. 8, 2019

33 WebMd.com How Long Is the Flu Contagious? Jan. 2, 2019

34  Pinsky BA, Mix S, Rowe J et al. Long-term Shedding of Influenza A Virus in Stool of Immunocompromised Child. Emerg Infect Dis 2010; 16 (7).

35 Suess T., Remschmidt C, Schink S et al. Comparison of Shedding Characteristics of Seasonal Influenza Virus (Sub) Types and Influenza A (H1N1) pdm09; Germany, 2007-2011.PLOS One 2012; 7(12).

36 Pinsky BA, Mix S, Rowe J et al. Long-term Shedding of Influenza A Virus in Stool of Immunocompromised Child. Emerg Infect Dis 2010; 16 (7).

37 Bouvier NM, Lowen AC. Animal Models for Influenza Virus Pathogenesis and Transmission. Viruses 2010; 2: 1530-1563

38 CDC. How Flu Spreads. Aug 27, 2018

39 Bischoff WE, Swett K et al. Exposure to Influenza Virus Aerosols During Routine Patient Care. J Infect Dis 2013; 207(7): 1037-1046.

40 WebMD. How Not to Spread the Flu. Sept. 16, 2018

41 CDC. How Flu Spreads. Aug 27, 2018

42 CDC. Influenza. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.

43 Potter CW. A History of Influenza. J. Appl. Microbiol 2001; 91(4): 572-579.

44 World Health Organization. What is a Pandemic. Feb. 24, 2010.

45 Potter CW. A History of Influenza. J. Appl. Microbiol 2001; 91(4): 572-579.

46 Short KR Katherine Kedzierska, K, van de Sandt CE Back to the Future: Lessons Learned From the 1918 Influenza Pandemic Front Cell Infect Microbiol. 2018; 8: 343.

47 CDC 1918 Pandemic (H1N1 virus) Mar. 20, 2019

48 Viboud C, Simonsen L, et al. Global Mortality Impact of the 1957-1959 Influenza Pandemic. J Infect Dis 2016 Mar 1;213(5):738-45.

49 DHHS. Pandemic Flu History.

50 Gaydos JC, Top FH, Hodder RA, Russell PK. Swine influenza A outbreak, Fort Dix, New Jersey, 1976. Emerg Infect Dis 2006; 12(1).

51 Mt. Sinai School of Medicine. 2009 swine flu pandemic originated in Mexico, researchers discover. Science Daily June 27, 2016.

52 The White House. Press Briefing On Swine Influenza. Apr. 26, 2009.

53  Roos R. HHS extends liability shield to antivirals used for H1N1. CIDRAP June 26, 2009.

54  NVIC. Pandemic H1N1 Swine Flu: What About You and Your Family. July 2009.

55  CDC 2009-2010 Influenza (Flu) Season. Sept. 8, 2010

56 CDC 2009 H1N1 Pandemic (H1N1pdm09 virus) Jun 11, 2019

57 CDC Selecting Viruses for the Seasonal Influenza Vaccine Sept. 4, 2018

58 CDC How the Flu Virus Can Change: “Drift” and “Shift” Sept. 27, 2017.

59 Biggerstaff M, Kniss K, Jernigan DB et al. Systematic Assessment of Multiple Routine and Near Real-Time Indicators to Classify the Severity of Influenza Seasons and Pandemics in the United States, 2003-2004 Through 2015-2016. Am J Epidemiol. 2018 May 1;187(5):1040-1050

60 CDC Estimates of Deaths Associated with Seasonal Influenza --- United States, 1976—2007. MMWR Aug. 27, 2010; 59(33);1057-1062.

61  Fisher BL. Influenza Deaths: The Hype vs. The Evidence. National Vaccine Information Center Oct. 3, 2012.

62 CDC. Estimates of Deaths Associated with Seasonal Influenza --- United States, 1976—2007. MMWR Aug. 27, 2010; 59(33);1057-1062.

63 CDC Influenza. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015

64 CDC Estimating Seasonal Influenza-Associated Deaths in the United States: CDC Study Confirms Variability of Flu Feb. 23, 2018

65 CDC Disease Burden of Influenza. Feb. 19, 2019

66 CDC Frequently Asked Questions about Estimated Flu Burden Nov. 5, 2018

67 Doshi P. Are U.S. Flu Death Figures More PR Than Science? BMJ 2005; 331 (7529): 1412

68 NVIC  Influenza & Pneumonia Reported Deaths in U.S. 1940-2010 (Chart).

69 CDC How CDC Estimates the Burden of Seasonal Influenza in the U.S. Oct. 25, 2018

70 Neel, J How Many People Die From Flu Each Year? Depends How You Slice The Data. NPR Aug. 26, 2010.

71 Johnson A, Zambon M. Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study The Lancet 2014; 445–454.

72 The Lancet Three-quarters of people with seasonal and pandemic flu have no symptoms AAAS Mar. 16, 2014.

73 Magalhaes I, Eriksson M, Linde C et al. Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic BMC Infectious Diseases 2014; 14: 319.

74 CDC. Influenza – Flu symptoms & Complications. Sept. 5, 2019

75 CDC. People at High Risk of Developing Flu–Related Complications Aug 27, 2018

76 WHO Influenza (Seasonal) Nov. 6, 2018

77 CDC How CDC Classifies Flu Severity Sept. 14, 2018

78 Dennis B. Flu vaccines: a mixture of hard science and good fortune. The Guardian Jan. 18, 2015.

79 CDC People at High Risk of Developing Flu–Related Complications. Aug. 27, 2018

80 CDC Personal NPIs: Everyday Preventive Actions Aug. 26, 2019

81 Mercola.com. How to Prevent the Flu -- as Easy as 1, 2, 3... Dec. 9, 2009.

82 Urashima M, Segawa T et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren Am J Clin Nutr  May 2010; 91(5):1255-1260.

83 CDC Nonpharmaceutical Interventions (NPIs) – At Home. Aug. 26, 2019

84 DerSarkissian C. 12 Natural Treatment Tips for Colds and Flu. WebMd Jul. 8, 2019

85 Malerba L. Homeopathy: A Time-Tested Treatment for the Flu. The Huffington Post May 25, 2011.

86 CDC What You Should Know About Flu Antiviral Drugs. Apr. 22, 2019

87 CDC How Influenza (Flu) Vaccines Are Made Sept. 24, 2018

88 CDC Thimerosal in Flu Vaccine. Oct. 16, 2015

89 CDC Quadrivalent Influenza Vaccine Sept. 6, 2019

90 CDC  Flu Vaccination by Jet Injector Sept. 12, 2019.

91 CDC Fluzone High-Dose Seasonal Influenza Vaccine Sept. 6, 2019

92 Simonsen L, Reichart T, Viboud C et al., Impact of Influenza Vaccination on Seasonal Mortality in the US Elderly Population Arch Intern Med 2005;165(3):265-272.

93 CDC How Influenza (Flu) Vaccines Are Made - Recombinant Flu Vaccines Sept. 24, 2018

94 CDC Recombinant Influenza (Flu) Vaccine Sept. 17, 2019

95 FDA Flublok Quadrivalent Influenza Vaccine Package Insert Jul. 2, 2019

96 CDC Cell-Based Flu Vaccines. Sept. 6, 2019

97 FDA Flucelvax Package Insert Jul. 2, 2019

98 FDA FLUAD Influenza Vaccine Package Insert Jul. 2, 2019

99NVIC Questions FDA Fast Tracking of Squalene Adjuvanted Flu Vaccine The Vaccine Reaction Sept. 16, 2016

100 CDC Flu Vaccine With Adjuvant - Flu Vaccine with Adjuvant, brand name FLUAD Sept. 4, 2019

101 CDC Intradermal Influenza (Flu) Vaccination. Oct. 31, 2018

102 FDA Fluzone Quadrivalent Intradermal Influenza Vaccine Package Insert. July 3, 2019

103 FDA June 17, 2003 Approval Letter - Influenza Virus Vaccine Live, Intranasal. June 17, 2003.

104 FDA September 19, 2007 Approval Letter - Influenza Virus Vaccine Live, Intranasal. Sept. 19, 2007.

105 CDC ACIP votes down use of LAIV for 2016-2017 flu season June 22, 2016.

106 Walker, M. ACIP Reinstates FluMist for 2018-2019 Flu Season. MEDPAGE TODAY Feb. 21, 2018

107 FDA FluMist Quadrivalent Influenza Vaccine Package Insert. July 15, 2019

108 FDA Pregnancy and Lactation Labeling (Drugs) Final Rule. Jun. 28, 2018.

109 Potter CW. A History of Influenza. J. Appl. Microbiol 2001; 91(4): 572-579.

110  CDC. Influenza. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.

111 Hannoun C. The Evolving History of Influenza Viruses and Influenza Vaccines Expert Rev Vaccines 2013;12(9):1085-1094.

112 Biondi E.A , Aligne A.C. Flu Vaccine for All: A Critical Look at the Evidence Medscape Pediatrics Dec. 21, 2015.

113 Hannoun C. The Evolving History of Influenza Viruses and Influenza Vaccines Expert Rev Vaccines 2013;12(9):1085-1094.

114 Stanley WM. The Preparation and Properties of Influenza Virus Vaccines Concentrated and Purified by Differential Centrifugation J Exp Med 1945; 81(2): 193–218.

115 Hampson AW. Vaccines for Pandemic Influenza. The History of our Current Vaccines, their Limitations and the Requirements to Deal with a Pandemic Threat Ann Acad Med Singapore 2008; 37:510-517.

116 Biondi E.A , Aligne A.C. Flu Vaccine for All: A Critical Look at the Evidence Medscape Pediatrics Dec. 21, 2015.

117 Henderson DA, Courtney B et al. Public health and medical responses to the 1957-58 influenza pandemic Biosecur Bioterror 2009;7:265-273.

118 Langmuir AD, Henderson DA, Serfling RE. The epidemiological basis for the control of influenza  Am J Public Health 1964; 54:563-571.

119 Schoenbaum SC, Mostow SR et al. Studies with inactivated influenza vaccines purified by zonal centrifugation. 2. Efficacy. Bull World Health Organ 1969; 41:531-535. 

120 Sencer DJ, Millar JD.  Reflections on the 1976 Swine Flu Vaccination Program. Emerg Infect Dis 2006; 12(1): 29–33.

121 Neustadt RE, Fineberg HV. The Swine Flu Affair: Decision-Making on a Slippery Disease. Washington (DC): National Academies Press (US) 1978.

122 Dowdle WR. The 1976 Experience. J Infect Dis 1997; 176 (Supplement 1): S69-S72.

123 Hannoun C. The Evolving History of Influenza Viruses and Influenza Vaccines. Expert Rev Vaccines 2013;12(9):1085-1094.

124 FDA. June 17, 2003 Approval Letter - Influenza Virus Vaccine Live, Intranasal. June 2003.

125 CDC Using Live, Attenuated Influenza Vaccine for Prevention and Control of Influenza: Supplemental Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Sept. 26, 2003, 52(RR13);1-8

126 Mallory RM, Yi T, Ambrose CS. Shedding of Ann Arbor strain live attenuated influenza vaccine virus in children 6-59 months of age. Vaccine 2011; 29(26): 4322-4327.

127  Fisher BL. The Emerging Risk of Live Virus and Virus Vectored Vaccines: Vaccine Strain Virus Infection, Shedding and Transmission. National Vaccine Information Center November 2014.

128 The White House Press Briefing On Swine Influenza. Apr. 26, 2009.

129 Griffen MR, Monto AS et al. Effectiveness of Non-Adjuvanted Pandemic Influenza A Vaccines for Preventing Pandemic Influenza Acute Respiratory Illness Visits in 4 U.S. Communities PloS One 2011; 6(8): e23085.

130 FDA Approval Letter - Fluzone High-Dose. Dec. 23, 2009.

131 CDC Fluzone High-Dose Seasonal Influenza Vaccine. Sept. 6, 2019

132 Lowes R. First Quadrivalent Flu Vaccine Approved, Debuts Fall 2013. Medscape Medical News Mar 1, 2012.

133 FDA Flucelvax Package Insert – Seqiris, Inc. Aug. 31, 2016.

134 CDC Cell-Based Flu Vaccines. Sept. 5, 2019

135 CDC Flublok Seasonal Influenza (Flu) Vaccine. Sept. 17, 2019.

136 FDA January 16, 2013 Approval Letter – Flublok Jan 16, 2013

137 FDA FluBlok Quadrivalent Package Insert July 2, 2019

138 FDA October 7, 2016 Approval Letter - Flublok Quadrivalent Oct. 7, 2016

139  Stobbe M. Ouch! Flu spray fails again, panel urges shot instead. Associated Press June 22, 2016.

140 CDC ACIP votes down use of LAIV for 2016-2017 flu season. June 22, 2016.

141 Walker, M. ACIP Reinstates FluMist for 2018-2019 Flu Season. MEDPAGE TODAY Feb. 21, 2018

142 CDC FLUAD™ Flu Vaccine With Adjuvant. Sept. 4, 2019

143NVIC Questions FDA Fast Tracking of Squalene Adjuvanted Flu Vaccine The Vaccine Reaction Sept. 16, 2016.

144 CDC Intradermal Influenza (Flu) Vaccination. Oct. 31, 2018

145 CDC Flu Vaccination by Jet Injector. Sept. 17, 2019

146 CDC Recommendation of the Immunization Practices Advisory Committee (ACIP) Prevention and Control of Influenza MMWR May 18, 1984; 33(19).

147  Fisher BL. Vaccination During Pregnancy: Is It Safe? National Vaccine Information Center Nov. 9, 2013.

148 CDC Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Apr. 25, 1997; 46(RR-9):1-25.

149 CDC Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR May 28, 2004; 53(RR06);1-40.

150 CDC Recommendations Regarding the Use of Vaccines That Contain Thimerosal as a Preservative. MMWR Nov. 5, 1999; 48(43):996-998.

151 CDC Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR May 28, 2004; 53(RR06);1-40.

152 CDC Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Aug. 6, 2010; 59(RR08):1-62.

153 CDC Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Aug. 26, 2011; 60(33):1128-1132.

154 CDC Flu Vaccine and People with Egg Allergies. Dec. 28, 2017

155 CDC Vaccine Recommendations and Guidelines of the ACIP: Contraindications and Precautions Aug. 20, 2019

156 CDC Past Seasons Vaccine Effectiveness Estimates Apr. 5, 2019

157 Demicheli V, Jefferson T et al. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews Mar. 13, 2014. 

158 Ibid.

159 Demicheli V, Jefferson T et al. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews. Feb 1, 2018

160 CDC Prevention and Control of Influenza with Vaccines – Recommendations of the Immunization Practices Advisory Committee (ACIP), 2010  MMWR Aug. 6, 2010. 59(RR08);1-62

161 Mayo Clinic Flu shot: Your best bet for avoiding influenza. Sept. 12, 2019

162 World Health Organization(WHO) Global Influenza Surveillance and Response System (GISRS). 2019.

163 CDC CDC Seasonal Flu Vaccine Effectiveness Studies Sept. 4, 2019

164 Simonsen L, Reichert TA, Viboud C, et al. Impact of Influenza Vaccination on Seasonal Mortality in the US Elderly Population Arch Intern Med 2005;165(3):265-272.

165 CDC CDC Seasonal Flu Vaccine Effectiveness Studies Sept. 4, 2019

166 Osterholm MT, Kelley NS et al. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012;12:36-44.

167 Skowronski DM, Chambers C et al. Interim estimates of 2014/15 vaccine effectiveness against influenza A(H3N2) from Canada's Sentinel Physician Surveillance Network, January 2015. Euro Surveill  2015 Jan 29;20(4).

168 Yourex-West H, McIntosh S, Canadian study finds flu shot could increase risk of getting sick. Global News. Jan. 30, 2015.

169 CDC. ACIP votes down use of LAIV for 2016-2017 flu season. June 22, 2016

170 Schnirring, L. CDC vaccine panel brings back FluMist for 2018-19 season. CIDRAP Feb. 21, 2018

171 CDC Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2019–20 Influenza Season MMWR August 23, 2019; 68(3);1–21

172  Perelman School of Medicine. H3N2 mutation in last year’s flu vaccine responsible for lowered efficacy. Medical Xpress Nov. 6, 2017.

173  Dwyer D. Q&A: Why the flu vaccine isn’t always effective. Boston Globe Dec. 7, 2017.

174 Demicheli V, Jefferson T, et al. Vaccines for preventing influenza in the elderly. Cochrane Database of Systematic Reviews. Feb. 1, 2018

175 Demicheli V, Jefferson T et al. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews Mar. 13, 2014.

176 Ibid.

177 Demicheli V, Jefferson T et al. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews. Feb 1, 2018

178 Flannery B Preliminary Estimates of 2018–19 Seasonal Influenza Vaccine Effectiveness against Medically Attended Influenza from three U.S. Networks Advisory Committee on Immunization Practices meeting June 27, 2019

179 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality. Evaluating Biological Mechanisms of Adverse Events (p. 57-102), Increased Susceptibility (p. 82). Washington, DC: The National Academies Press 2012.

180 CDC Inactivated Influenza VIS Aug. 15, 2019

181  Kwong JC, Vasa PP et al. Risk of Guillain Barre Syndrome after seasonal influenza vaccinations and influenza health care encounters: a self-controlled study. The Lancet Infectious Diseases 2013; 13(9): 769-776.

182  GBS Flu Vaccine Reaction Leaves Nurse A Quadriplegic. National Vaccine Information Center Oct. 31, 2011.

183 CDC Guillain-Barré syndrome and Flu Vaccine. Oct. 16, 2015

184 Van den Berg B, Bunschoten C et al. Mortality in Guillain-Barré Syndrome. Neurology 2013; 80(18): 1650-1654

185 CDC Flu Vaccine Safety Information Oct. 5, 2017.

186 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality. (Evaluating Biological Mechanisms for Adverse Events: Increased Susceptibility). Washington, DC: The National Academies Press. 2012

187 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality. (Evaluating Biological Mechanisms for Adverse Events: Increased Susceptibility). Washington, DC: The National Academies Press. 2012. Chap. 6 p.293-420

188 Ibid

189 Department of Health and Human Services. Advisory Committee on Childhood Vaccines (ACCV) Meeting. Mar. 3, 2011.

190 HRSA Vaccine Injury Compensation Program Data and Statistics Sept. 1, 2019

191 HRSA Vaccine Injury Table Mar. 21, 2017

192 Huynh W, Cordato DJ, Kehdi E et al. Post-vaccination encephalomyelitis: literature review and illustrative case. J Clin Neurosci. 2008 Dec;15(12):1315-22.

193 Nakamura N, Nokura K, Zettsu T et al. Neurologic complications associated with influenza vaccination: two adult cases. Intern Med. 2003 Feb;42(2):191-4.

194 Shoamanesh A, Traboulsee A. Acute disseminated encephalomyelitis following influenza vaccination. Vaccine. 2011 Oct 26;29(46):8182-5

195 Lee ST, Choe YJ, Moon WJ, et al. An adverse event following 2009 H1N1 influenza vaccination: a case of acute disseminated encephalomyelitis. Korean J Pediatr. 2011 Oct;54(10):422-4

196 Maeda K, Idehara R. Acute disseminated encephalomyelitis following 2009 H1N1 influenza vaccination. Intern Med. 2012;51(14):1931-3.

197 Machicado JD, Bhagya-Rao B, Davogustto G, McKelvy BJ. Acute disseminated encephalomyelitis following seasonal influenza vaccination in an elderly patient. Clin Vaccine Immunol. 2013 Sep;20(9):1485-6.

198 Arai M, Takagi D, Nagao R. Acute disseminated encephalomyelitis following influenza vaccination: report of a case with callosal disconnection syndrome. Rinsho Shinkeigaku. 2014;54(2):135-9.

199 Andrade SD, Andrade MG, Santos PJ et al. Acute disseminated encephalomyelitis following inactivated influenza vaccination in the Brazilian Amazon: a case report. Rev Soc Bras Med Trop. 2015 Jul-Aug;48(4):498-500

200 Ravaglia S, Ceroni M, Moglia A et al. Post-infectious and post-vaccinal acute disseminated encephalomyelitis occurring in the same patients. J Neurol. 2004 Sep;251(9):1147-50.

201 Hoshino T, Uchiyama Y, Ito E, et al. Simultaneous development of acute disseminated encephalomyelitis and Guillain-Barré syndrome associated with H1N1 09 influenza vaccination. Intern Med. 2012;51(12):1595-8.

202 Vainer-Mossel ED, Mekori YA, Mor A. Ischemic stroke in a patient with lupus following influenza vaccination: a questionable association. Isr Med Assoc J. 2009 Mar;11(3):186-7.

203 Taras JS, Donohue KW Radial nerve motor palsy following seasonal influenza vaccination: a case report. J Surg Orthop Adv. 2014 Spring;23(1):42-4.

204 Shaikh MF, Baqai TJ, Tahir H. Acute brachial neuritis following influenza vaccination. BMJ Case Rep. 2012 Nov 28;2012

205 Antony SJ, Fleming DF, Bradley TK. Postvaccinial (influenza) disseminated encephalopathy (Brown-Sequard syndrome) J Natl Med Assoc. 1995 Sep;87(9):705-8.

206 Asakawa J, Kobayashi S, Kaneda K, et al. Reactive arthritis after influenza vaccination: report of a case. Mod Rheumatol. 2005;15(4):283-5.

207 Walmsley N, Hampton P Bullous pemphigoid triggered by swine flu vaccination: case report and review of vaccine triggered pemphigoid J Dermatol Case Rep. 2011 Dec 12; 5(4): 74–76.

208 Lear JT, Tan BB, English JS. Bullous pemphigoid following influenza vaccination. Clin Exp Dermatol. 1996 Sep;21(5):392.

209 Fournier B, Descamps V, Bouscarat F, et al. Bullous pemphigoid induced by vaccination. Br J Dermatol. 1996 Jul;135(1):153-4.

210 Downs AM, Lear JT, Bower CP, Kennedy CT Does influenza vaccination induce bullous pemphigoid? A report of four cases. Br J Dermatol. 1998 Feb;138(2):363.

211 Byrd RC, Mournigham KJ, Baca-Atlas M, Generalized Bullous fixed-drug eruption secondary to influenza vaccine JAAD Case Reports 2018 Oct 12; 4(9): 953-955.

212 Al-Mutairi N, Al-Fouzan A, Nour-Eldin O. Fixed drug eruption due to influenza vaccine. J Cutan Med Surg. 2004 Jan-Feb;8(1):16-8

213 García-Doval I, Rosón E, Feal C et al. Generalized bullous fixed drug eruption after influenza vaccination, simulating bullous pemphigoid. Acta Derm Venereol. 2001 Nov-Dec;81(6):450-1.

214 Hull JH, Mead SH, Foster OJ et al. Severe vasculitic neuropathy following influenza vaccination. J Neurol Neurosurg Psychiatry. 2004 Oct;75(10):1507-8.

215 Mader R, Narendran A, Lewtas J et al. Systemic vasculitis following influenza vaccination--report of 3 cases and literature review. J Rheumatol. 1993 Aug;20(8):1429-31.

216 Blumberg S, Bienfang D, Kantrowitz FG. A possible association between influenza vaccination and small-vessel vasculitis. Arch Intern Med. 1980 Jun;140(6):847-8.

217 Duggal T, Segal P, Shah M et al. Antineutrophil cytoplasmic antibody vasculitis associated with influenza vaccination. Am J Nephrol. 2013;38(2):174-8

218 Ritter O1, Bonz A, Strotmann J, Langenfeld H. Myocardial infarction after influenza vaccination. Z Kardiol. 2003 Nov;92(11):962-5.

219 Bakshi R, Mazziotta JC. Acute transverse myelitis after influenza vaccination: magnetic resonance imaging findings. J Neuroimaging. 1996 Oct;6(4):248-50.

220 Sato N, Watanabe K, Ohta K, Tanaka H. Acute transverse myelitis and acute motor axonal neuropathy developed after vaccinations against seasonal and 2009 A/H1N1 influenza. Intern Med. 2011;50(5):503-7.

221 Vieira MA, Costa CH, Vieira CP et al. Transverse myelitis with Brown-Sèquard syndrome after H1N1 immunization. Arq Neuropsiquiatr. 2012 Jul;70(7):555.

222 Nakamura N, Nokura K, Zettsu T et al. Neurologic complications associated with influenza vaccination: two adult cases. Intern Med. 2003 Feb;42(2):191-4.

223 Cho JH, Park Y, Woo N. A case of neuromyelitis optica spectrum disorder following seasonal influenza vaccination. Mult Scler Relat Disord. 2019 May;30:110-113.

224 Jun B, Fraunfelder FW Atypical Optic Neuritis After Inactivated Influenza Vaccination. Neuroophthalmology. 2017 Aug 17;42(2):105-108

225 Hull TP, Bates JH. Optic neuritis after influenza vaccination. Am J Ophthalmol. 1997 Nov;124(5):703-4.

226 Chou CH, Liou WP, Hu KI Bell's palsy associated with influenza vaccination: two case reports. Vaccine. 2007 Apr 12;25(15):2839-41.

227 Institute of Medicine Committee to Review Adverse Effects of Vaccines  Adverse Effects of Vaccines Evidence and Causality. Influenza Vaccine. pp 293-420.  Washington, D.C. The National Academies Press 2012.

228 Skowronski DM, Chambers C et al. Interim estimates of 2014/15 vaccine effectiveness against influenza A(H3N2) from Canada's Sentinel Physician Surveillance Network, January 2015. Euro Surveill  2015 Jan 29;20(4).

229 Yourex-West H, McIntosh S, Canadian study finds flu shot could increase risk of getting sick. Global News. Jan. 30, 2015.

230 CDC Flu Vaccination & Addressing Concerns Pregnant Women Might Have about Flu Vaccine Safety July. 5, 2019

231 Wrangham, T ACIP: 2018-2019 Flu Vaccine 44 Percent Effective National Vaccine Information Center Apr. 7, 2019

232 Kessler DA, the Working Group, Natanblut S, et al. A New Approach to Reporting Medication and Device Adverse Effects and Product Problems. JAMA. 1993;269(21):2765-2768.

233 FDA.gov. Kessler DA. Introducing MEDWatch: A New Approach to Reporting Medication and Device Adverse Effects and Product Problems. Reprint from JAMA. June 9, 1993.

234 Braun M. Vaccine adverse event reporting system (VAERS): usefulness and limitations. Johns Hopkins Bloomberg School of Public Health

235 Rosenthanl S, Chen R. The reporting sensitivities of two passive surveillance systems for vaccine adverse events. Am J Public Health 1995; 85: pp. 1706-9.

236 AHRQ Electronic Support for Public Health–Vaccine Adverse Event Reporting System (ESP:VAERS) Dec 1, 2007-Sep. 30, 2010

237 U.S. Department of Health and Human Services. National Vaccine Injury Compensation Program Data—September 1, 2019. National Vaccine Injury Compensation Program. Sept 1, 2019

238  Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality: Evaluating Biological Mechanisms of Adverse Events (p. 57-102), Increased Susceptibility (p. 82). Washington, DC: The National Academies Press 2012.

239  CDC Vaccine Recommendations and Guidelines of the ACIP: Contraindications and Precautions. Aug. 20, 2019

240 FDA Flucelvax Package Insert Aug. 31, 2016

241 FDA Flublok Quadrivalent Package Insert July 2, 2019

242 CDC Flu Vaccine and People with Egg Allergies Dec. 28, 2017

243 CDC Prevention and Control of Seasonal Influenza with Vaccines Recommendations of the Advisory Committee on Immunization Practices — United States, 2016–17 Influenza Season MMWR Aug. 26, 2016; 65(5):1–54.

244 CDC. Flu Vaccine and People with Egg Allergies Dec. 28, 2017

245  CDC. Vaccine Recommendations and Guidelines of the ACIP: Contraindications and Precautions. Aug. 20, 2019

246 FDA FluMist Quadrivalent Package Insert July 15, 2019

247 Fisher, BL The Emerging Risks of Live Virus & Virus Vectored Vaccines: Vaccine Strain Virus Infection, Shedding & Transmission The National Vaccine Information Center 2014

248 CDC. ACIP votes down use of LAIV for 2016-2017 flu season. Jun. 22, 2016

249 Walker, M. ACIP Reinstates FluMist for 2018-2019 Flu Season. MEDPAGE TODAY Feb. 21, 2018

250 CDC Live, Intranasal Influenza VIS  Aug. 15, 2019

251 CDC Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2019–20 Influenza Season MMWR Aug. 23, 2019; 68(3);1–21

252 Immunize.org State Information - Influenza Vaccine Mandates for Children in Child Care Facilities Nov. 11, 2018

253 CDC Flu Vaccination & Addressing Concerns Pregnant Women Might Have about Flu Vaccine Safety July 5, 2019

254 U.S. Dept. of Health & Human Services. FDA Pregnancy Categories. Jun. 26, 2019

255 FDA. Pregnancy and Lactation Labeling (Drugs) Final Rule. Jun. 28, 2018

256 Gruber MF Maternal Immunization: US FDA Regulatory Considerations (Abstract) Vaccine 2003; 21(24): 3487-3491.

257 Christian LM, Iams JD et al. Inflammatory Responses to Trivalent Influenza Virus Vaccine Among Pregnant Women. Vaccine 2011; 29(48): 8982-8987.

258 Ayoub D Yazbak FE. Influenza vaccination during pregnancy: A critical Assessment of the Recommendations of the Advisory Committee on Immunization Practices (ACIP). Journal of American Physicians & Surgeons 2006; 11(2): 41-47.

259 Elce D, Celik A. Genotoxicity of thimerosal in cultured human lymphocytes with and without metabolic activation sister chromatid exchange analysis proliferation index and mitotic index. Toxicology in Vitro June 2008; 22(4): 927-934.

260 Businesswire. National Vaccine Information Center (NVIC) Calls 21st Century Cures Act “A Wolf in Sheep’s Clothing” and Urges Presidential Veto to Protect Public Health. NVIC Press Release Dec. 8, 2016.

261 Feemster KA. Advisory Commission on Childhood Vaccines Maternal Immunization Working Group Draft Recommendations. ACCV June 7, 2013.

262 CDC Flu Vaccination & Addressing Concerns Pregnant Women Might Have about Flu Vaccine Safety July. 5, 2019

263 Wrangham, T ACIP: 2018-2019 Flu Vaccine 44 Percent Effective National Vaccine Information Center Apr. 7, 2019

264 FDA Thimerosal in Vaccines Feb. 1, 2018.

265 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Immunization Safety Review: Thimerosal - Containing Vaccines and Neurodevelopmental Disorders. Washington, D.C. The National Academies Press 2001.


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