Exhaustive RAND Corporation review of vaccine side effects finds strong evidence that vaccines cause Guillain-Barre Syndrome, myalgia, seizures, meningitis, encephalitis and more

Diphtheria Toxoid, Tetanus Toxoid, and Acellular Pertussis Vaccines (Td, Tdap)
High: Anaphylaxis
Evidence “convincingly supports” a causal relationship between the tetanus toxoid vaccine and anaphylaxis.
We identified 2 additional trials in adults. No AEs were associated with vaccine.
Hepatitis A Vaccine
Insufficient: Acute disseminated encephalomyelitis, transverse myelitis, MS, GBS, chronic inflammatory demyelinating polyneuropathy, Bell’s palsy, anaphylaxis, and autoimmune hepatitis
Evidence is “inadequate to accept or reject” any causal relationships with AEs the committee was tasked with investigating: acute disseminated encephalomyelitis, transverse myelitis, MS, GBS, chronic inflammatory demyelinating polyneuropathy, Bell’s palsy, anaphylaxis, and autoimmune hepatitis.
We identified 1 additional postlicensure study; there was no association of the vaccine with any AEs or onset of medical conditions.
Hepatitis B Vaccine

• Insufficient: Optic neuritis, first demyelinating event, GBS, SLE, onset or exacerbation of vasculitis, polyarteritis nodosa, and onset or exacerbation of rheumatoid arthritis


• Moderate: No association with MS onset or exacerbation


• Moderate: Anaphylaxis in patients allergic to yeast

• Although no epidemiological studies were identified on anaphylaxis, mechanistic evidence “favors acceptance” of a causal relationship between the vaccine and anaphylaxis in yeast-sensitive individuals.


• Epidemiological studies of the following AEs in adults had evidence “inadequate to accept or reject” a causal relationship: optic neuritis, first demyelinating event, GBS, SLE, onset or exacerbation of vasculitis, polyarteritis nodosa, and onset or exacerbation of rheumatoid arthritis.


• A 2002 IOM review on Hep B vaccine and demyelinating neurological disorders concluded that the evidence “favors rejection” of a causal relationship with incident MS or MS relapse.


• No epidemiological studies of the following AEs in adults were found and evidence is also “inadequate to accept or reject” a causal relationship: encephalitis, encephalopathy, ADEM, transverse myelitis, neuromyelitis optica, chronic inflammatory demyelinating polyneuropathy, brachial neuritis, erythema nodosum, onset or exacerbation of psoriatic arthritis, onset or exacerbation of reactive arthritis, and fibromyalgia.

No additional studies met our inclusion criteria.
Influenza Vaccines

• High: Arthralgia, myalgia, malaise, fever, pain at injection site. Anaphylaxis in allergic persons.


• High: 2009 monovalent H1N1 vaccine with GBS


• High: No association with cardiovascular events in the elderly


• Insufficient: MS onset and exacerbation

• Two forms of influenza vaccine were studied: live attenuated form, administered intranasally (LAIV), and inactivated form (TIV), administered intramuscularly.


• Evidence “convincingly supports” a causal relationship between influenza vaccines and anaphylaxis in people allergic to egg or gelatin. However, in recent years, manufacturers have reduced the egg protein content.

• Many clinical trials reported that influenza vaccines are associated with arthralgia, myalgia, malaise, fever, and pain in the short term in adults. These AEs were not considered serious; severity was graded mild to moderate. Odds of experiencing these events were 1.5 to 2 times higher in vaccinated patients than in unvaccinated people. Risk factors were not discussed in the trials.


• A high-quality meta-analysis found an association between 2009 monovalent H1N1 vaccine and GBS in the 42 days postvaccination; results translate to about 1.6 excess cases per million vaccinated.


• Postlicensure studies have found inconsistent evidence associating influenza vaccines with onset or exacerbation of MS in adults.


• Postlicensure studies have found influenza vaccines are NOT associated with increased risk of cardiovascular or cerebrovascular events in the elderly.


• Postlicensure studies have shown that influenza vaccines are NOT associated with increased risk of serious AEs in renal patients.

MMR Vaccine

• Moderate: No association with Type 1 diabetes


• Moderate: Transient arthralgia in women


• Insufficient: MS onset, GBS, chronic arthralgia in women, and chronic arthritis and arthropathy in men

• Evidence “favors acceptance” of a causal relationship with transient arthralgia in women.


• Evidence is “inadequate to accept or reject” a causal relationship with MS onset, GBS, chronic arthralgia in women, and chronic arthritis and arthropathy in men.

MMR was NOT associated with onset of type 1 diabetes in adults in 1 large high-quality epidemiological study: RR=0.71 (95% CI, 0.61 to 0.83).
Pneumococcal Polysaccharide Vaccine
High: No association with cardiovascular or cerebrovascular events in the elderly
Not covered.

• We found no placebo-controlled trials of the current formulation that reported AE data. (We found trials of the current formulation that reported pneumonia or mortality; these were considered efficacy outcomes.)


• Postlicensure studies of pneumococcal polysaccharide vaccine found vaccination was not associated with increased risk of cardiovascular events in older adults.

Zoster Vaccine
Moderate: Injection site reactions, allergic reactions, cellulitis possibly related to allergy
Recommended for U.S. adults 60 years and older; AEs specific to this age group were not covered.

• In some reports of clinical trials, AEs were reported only in categories such as “injection-related adverse events,” “systematic adverse events,” or “serious adverse events.” Vaccination was associated with injection site reactions.


• In postlicensure studies, vaccination was associated with cellulitis possibly related to allergy and allergic reactions such as redness and swelling 1 to 7 days postvaccination. These mild AEs occurred in less than 1% of patients and were more likely in the younger (aged 50-59) vaccinees.

Diphtheria Toxoid, Tetanus Toxoid, and Acellular Pertussis-Containing Vaccines (DTap, Td, Tdap)

• Moderate: No association with type 1 diabetes


• Insufficient: Infantile spasms, seizures, cerebellar ataxia, autism, ADEM, transverse myelitis, MS relapse, serum sickness, immune thrombocytopenic purpura, and SIDS

• Evidence “favors rejection” of a causal relationship between vaccines containing diphtheria toxoid, tetanus toxoid, and acellular pertussis antigens and type 1 diabetes.


• Evidence is “inadequate to accept or reject” causal relationships between vaccination and the following: infantile spasms, seizures, cerebellar ataxia, autism, ADEM, transverse myelitis, MS relapse in children, serum sickness, immune thrombocytopenic purpura, and SIDS.

We found no additional studies that met our inclusion criteria.
Hepatitis B Vaccine

• Insufficient: Food allergy


• Moderate: No association with MS

• Although no epidemiological studies were identified by the IOM, mechanistic evidence “favored acceptance” of a causal relationship between the vaccine and anaphylaxis in yeast-sensitive individuals. The IOM found evidence “inadequate to accept or reject” a causal relationship with any other AEs.


• A 2002 IOM report “favors rejection” of a causal relationship with MS onset or exacerbation.

Hep B vaccine in the first 6 months of life was associated with elevated total IgE in a postlicensure study of children with a family history of food allergy, but not with clinical allergy.
Hib Vaccine
Moderate: No association with serious AEs in short term
Not covered.
No serious AEs were associated in 3 high-quality clinical trials.
HPV Vaccine

• Moderate: No association with juvenile rheumatoid arthritis, type 1 diabetes, appendicitis, GBS, seizures, stroke, syncope, venous thromboembolism


• Moderate: Anaphylaxis in persons with allergies, fever, headache, mild gastrointestinal AEs, skin infection


• High: Pain at injection site


• Insufficient: ADEM, transverse myelitis, neuromyelitis optica, MS, onset of Hashimoto’s disease, chronic inflammatory demyelinating polyneuropathy, brachial neuritis, amyotrophic lateral sclerosis, transient arthralgia, pancreatitis, thromboembolic events, spontaneous abortion, and hypercoagulable states

• Evidence “favors acceptance” of a causal relationship between the HPV vaccine and anaphylaxis.


• Evidence is “inadequate to accept or reject” causal relationships between HPV vaccines and the following: ADEM, transverse myelitis, neuromyelitis optica, MS, GBS, chronic inflammatory demyelinating polyneuropathy, brachial neuritis, amyotrophic lateral sclerosis, transient arthralgia, pancreatitis, thromboembolic events, and hypercoagulable states.

• A large postlicensure study found HPV vaccine was not associated with onset of juvenile rheumatoid arthritis or type 1 diabetes. This study reported an IRR of 1.29 (95% CI, 1.08 to 1.56) of onset of Hashimoto’s disease. However, investigation of a temporal relationship and biological plausibility revealed no consistent evidence of a safety signal.


• A large postlicensure study found HPV vaccine was NOT associated with GBS, seizures, stroke, syncope, or venous thromboembolism.


• Several clinical trials found HPV vaccination associated with short-term severe pain at injection site. Trials also found vaccine associated with fever, headache, nausea, and stomach ache.


• A secondary analysis including only Black women who became pregnant within 3 to 4 years of receiving HPV vaccine in 2 trials reported a higher rate of spontaneous abortion in vaccinated subjects.

Inactivated Polio Vaccine
Insufficient: Food allergy
Not covered.
One postlicensure study reported association between polio vaccine in newborns and sensitivity to food allergens.
Influenza Vaccines

• Moderate: Mild gastrointestinal disorders, febrile seizures


• Low: No association with any serious AEs in the short term in children with cancer or who have received organ transplants


• Low: Influenza-like symptoms


• Insufficient: Asthma exacerbation (with live vaccine), ADEM, transverse myelitis

• The IOM committee studied seasonal influenza vaccines. The influenza vaccine is administered in 2 forms: a live attenuated form, administered intranasally, and an inactivated form, administered intramuscularly.


• Evidence was “inadequate to accept or reject” a causal relationship in the pediatric population between seasonal influenza vaccines and the following: seizures, ADEM, and transverse myelitis.


• Evidence was “inadequate to accept or reject” a causal relationship between LAIV and asthma exacerbation or reactive airway disease episodes.

• In postlicensure studies, seasonal influenza vaccines were NOT associated with any serious adverse events in the short term in children with malignancy, inflammatory bowel disease, or urea cycle disorders, or children who had received organ transplants.


• Both seasonal influenza vaccines and monovalent H1N1 vaccine were associated with mild gastrointestinal disorders, such as vomiting and diarrhea, in children in the short term in several large postlicensure studies. One large study found that younger vaccinated children (aged 5 to 8 years) were more likely to experience these symptoms than older vaccinated children (aged 9 to 17 years). (Children under 5 years of age were not included in that study).


• Both live and inactivated seasonal influenza vaccines were associated with influenza-like symptoms in children in the short term in multiple studies, while not associated in others. A large U.S. postlicensure study of children under age 5 years found TIV associated with febrile seizures. Risk was increased if PCV13 was administered concomitantly.

MMR Vaccine

• High: No association with autism spectrum disorders


• High: Anaphylaxis in children with allergies, febrile seizures


• Moderate: Transient arthralgia


• Moderate: Thrombocytopenic purpura


• Insufficient: Encephalitis, encephalopathy, afebrile seizures, meningitis, cerebellar ataxia, acute disseminated encephalomyelitis, transverse myelitis, optic neuritis, neuromyelitis optica, MS onset, and chronic arthropathy

• Evidence “convincingly supports” causal relationships with febrile seizures and anaphylaxis. Evidence “convincingly supports” a causal relationship with measles inclusion body encephalitis in immunocompromised patients.


• Evidence “favors acceptance” of a causal relationship between MMR and transient arthralgia


• Evidence “favors rejection” of a causal relationship between MMR and autism.


• Evidence is “inadequate to accept or reject” a causal relationship with encephalitis, encephalopathy, afebrile seizures, cerebellar ataxia, acute disseminated encephalomyelitis, transverse myelitis, optic neuritis, neuromyelitis optica, MS onset, and chronic arthropathy.

Four additional postmarketing studies were identified. Vaccination was associated with thrombocytopenic purpura in the short term. MMR vaccination was associated with increased emergency department visits within 2 weeks; this is indirect support of the IOM’s findings that MMR vaccine is associated with febrile seizures.
Meningococcal Vaccines (MCV4, MPSV)

• Moderate: Anaphylaxis in children with allergies


• Insufficient: Encephalitis, encephalopathy, ADEM, transverse myelitis, MS, GBS, CIDP, chronic headache

• Evidence “convincingly supports” a causal relationship with anaphylaxis in children who may be allergic to ingredients.


• Evidence is “inadequate to accept or reject” causal relationships between meningococcal vaccine (unspecified) and the following: encephalitis, encephalopathy, ADEM, transverse myelitis, MS, GBS, CIDP, and chronic headache.

Two new trials of quadrivalent meningococcal conjugate vaccines found no association with any AEs assessed.
Miscellaneous and Combination Vaccines

• Moderate: DTaP-IPV-Hib vaccination with febrile seizures


• High: No association of childhood leukemia with MMR, DTaP, Td, Hib, Hep B, and polio vaccines


• Moderate: Hepatitis A, MMR, and varicella vaccine with purpura

Not covered.

• Association of DTaP-IPV-Hib vaccination with febrile seizures in children was found in a very large high-quality postlicensure study. Rate for first dose was estimated as 5.5 cases per 100,000 person/days. Rate for second dose was estimated as 5.7 cases per 100,000 person/days.


• Multiple large epidemiological studies have assessed MMR, DTaP, Td, Hib, Hep B, and polio vaccine and have found no association with childhood leukemia.


• In a large postlicensure study of over 1.8 million vaccine recipients, purpura was associated with vaccination against hepatitis A in children aged 7 to 17 years, vaccination against varicella in children aged 11 to 17, and MMR in children from 12 to 19 months of age. These results were based on 1 or 2 cases per vaccine type/age group. According to the authors most cases were mild and acute.

Pneumococcal Conjugate (PCV13)
Moderate: Febrile seizures
Not covered.
A recent study using the U.S. Vaccine Safety Datalink (VSD) found an association with febrile seizures. Estimated rate for 16-month-old patients is 13.7 cases per 100,000 doses for PCV13 without concomitant TIV and 44.9 per 100,000 doses for concomitant TIV and PCV13.
Rotavirus Vaccines: RotaTeq and Rotarix
Moderate: Intussusception
Not covered.

• In clinical trials, there was no association between either of the 2 currently available vaccines (RotaTeq and Rotarix) and any serious AEs, including intussusception, in the long or short term.


• A high-quality epidemiological study in Australia found RotaTeq was associated with intussusception 1 to 21 days following the first of 3 required doses in infants 1 to 3 months of age. Two case-control studies conducted in Latin America found an association of Rotarix with intussusception in children following the first of 2 required doses. Although 1 U.S. epidemiological study found no association, a recent analysis of the U.S. Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program found both RotaTeq and Rotarix associated with intussusception in the short term. Estimated rate was 1.1 to 1.5 cases per 100,000 doses of RotaTeq and 5.1 cases per 100,000 doses of Rotarix.

Varicella Vaccine

• High: Anaphylaxis; disseminated Oka VZV without other organ involvement; disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis in individuals with demonstrated immunodeficiencies; vaccine strain viral reactivation without other organ involvement; vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis


• Insufficient: Seizures, ADEM, transverse myelitis, GBS, small fiber neuropathy, onset or exacerbation of arthropathy, thrombocytopenia

• Evidence “convincingly supports” causal relationships between varicella virus vaccine and the following: disseminated Oka VZV without other organ involvement; disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis in individuals with demonstrated immunodeficiencies; vaccine strain viral reactivation without other organ involvement; vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis; and anaphylaxis.


• The evidence is “inadequate to accept or reject” a causal relationship between the vaccine and seizures, ADEM, transverse myelitis, GBS, small fiber neuropathy, onset or exacerbation of arthropathy, and thrombocytopenia.

We identified 1 small trial in children with SLE; the trial reported no association with AEs.
Influenza Vaccines
Moderate: No association with serious adverse events
Results not specific to pregnant women.
Both monovalent H1N1 vaccine and seasonal influenza vaccine (inactivated) containing H1N1 strains were not associated with serious adverse events in pregnant women or their offspring in multiple trials and postlicensure studies. Studies report an association with lower risk of adverse pregnancy outcomes.