Vaccine Adverse Events (AEFI)

• Vaccines in national immunization programs are generally safe and effective, but no immune response is risk-free.

Adverse Events Following Immunization (AEFI)

• AEFI is an untoward medical occurrence following immunization, not necessarily causally related to the vaccine.
• Adverse events can be unfavorable signs, abnormal lab results, symptoms, or diseases.
• Reported adverse events can be true adverse events (caused by the vaccine/immunization), or coincidental events (temporally associated, but not caused by the vaccine/immunization).
• In 2012, CIOMS and WHO revised AEFI classifications for cause-specific categorization.

Types of AEFI

• Vaccine product-related reaction: caused by inherent properties of the vaccine.
• Example: Extensive limb swelling after DTP vaccination.
• Vaccine quality defect-related reaction: caused by quality defects in vaccine product/administration device.
• Example: Paralytic polio due to failure to inactivate polio vaccine completely.
• Immunization error-related reaction: caused by improper vaccine handling, prescribing, or administration and is preventable.
• Example: Transmission of infection via contaminated multidose vial.
• Immunization anxiety-related reaction: arises from anxiety about immunization.
• Example: Vasovagal syncope in adolescents during/following vaccination.
• Coincidental event: caused by something other than the vaccine, immunization error, or anxiety.
• Example: Fever at vaccination time caused by malaria.
• Coincidental events reflect the natural occurrence of common health problems.

Vaccine Reactions

• New categorization differentiates between reactions to inherent vaccine properties and defects during manufacturing.
• Vaccine Product-Related Reaction: Individual's response to the vaccine's inherent properties when prepared, handled, and administered correctly.
• Vaccine Quality Defect-Related Reaction: Defect in vaccine manufacturing, may impact individual response and increase the risk of adverse reactions.
• Vaccine reactions are classified into common, minor reactions or rare, more serious reactions. Most are minor and resolve on their own; serious reactions are rare and don't generally cause long-term issues.

Common, Minor Vaccine Reactions

• Vaccines induce immunity, causing the immune system to react, resulting in local reaction, fever, and systemic symptoms.
• Vaccine components like aluminum adjuvant, stabilizers, or preservatives can also lead to reactions.
• Successful vaccines minimize reactions while optimizing immunity.
• Local reactions: pain, swelling, and/or redness at the injection site (expected in ~10% of vaccinees, higher for DTP or tetanus boosters).
• BCG causes a specific local reaction starting as a papule, then ulcerating and healing into a scar, and keloid scarring is more common in Asians and Africans.
• Systemic reactions: fever (in ≤10% of vaccinees, higher for DTP), irritability, malaise, "off-color" appearance, and loss of appetite can occur after DTP.
• Measles/MMR/OPV cause reactions due to vaccine virus infection.
• Measles vaccine: fever, rash, and/or conjunctivitis (5-15% of vaccinees, mild compared to wild measles, but can be severe/fatal in immunocompromised individuals).
• Mumps vaccine: swollen parotid gland (<1% of children).
• Rubella vaccine: joint pains and swollen lymph nodes (more common in adults, with 15% experiencing joint pains).
• OPV: diarrhea, headache, and/or muscle pain (<1% of vaccinees).

Common minor vaccine reactions summary

• BCG: Local reaction (pain, swelling, redness) is common. Oral presentation-none.
• Cholera: Local reaction (pain, swelling, redness), up to 50%.
• DTP: Fever, up to 50%.
• Hepatitis A: Local reaction (pain, swelling, redness), up to 50%.
• Hepatitis B: Local reaction (pain, swelling, redness), up to 5%. Fever: 30% in children, up to 1-6% in adults.
• Hib: Local reaction (pain, swelling, redness), 5-15%. Fever, 2-10%.
• Japanese Encephalitis: Local reaction, low-grade fever, myalgia, gastrointestinal upset, up to 20%.
• Measles/MMR: Local reaction (pain, swelling, redness), up to 10%. Irritability, malaise, non-specific symptoms, fever, up to 5%.
• Pneumococcal: Local reaction (pain, swelling, redness), 30-50%.
• Poliomyelitis (OPV/IPV): None.
• Rabies: Local and/or general reaction depending on type of vaccine.
• Meningococcal disease: Mild local reactions, up to 71%.
• Tetanus/Td: Local reaction (pain, swelling, redness), up to 10%. Malaise and non-specific symptoms, up to 25%.
• Tick-borne encephalitis: Upto 10%.
• Typhoid fever: depends on type of vaccine used.
• Yellow fever: Headache 10%. Influenza-like symptoms 22%. Local reaction (pain, swelling, redness) 5%.
• The rate of local reactions is likely to increase with booster doses, up to 50-85%.
• Whole-cell pertussis vaccines have a higher local reaction.

Rare, More Serious Vaccine Reactions

• Serious and severe are not interchangeable terms.
• An AEFI is considered serious if it results in death, is life-threatening, requires hospitalization, results in disability, is a congenital anomaly, or requires intervention to prevent permanent impairment
• Severe describes the intensity of an event (mild, moderate, or severe).
• Inconsolable screaming, thrombocytopenia, and HHES do not lead to long-term problems.
• Anaphylaxis, while potentially fatal, is treatable without leaving any long-term effects.
• Encephalopathy as a reaction of certain vaccines is unconfirmed.

Rare vaccine reaction summary

• BCG: Suppurative lymphadenitis (2-6 months, 1-10/104), BCG osteitis (1-12 months, 1-700/106), Disseminated BCG infection (1-12 months, 0.19-1.56/106).
• Hepatitis B: Anaphylaxis (0-1 hour, 1.1/106).
• Influenza (inactivated): Anaphylaxis (0.7/106), Guillain-Barre syndrome (GBS) (1-2/106), Oculo-respiratory syndrome (76/106).
• Influenza (live-attenuated): Anaphylaxis (2/106), Wheezing in children (6-11 months) (14.100).
• Japanese encephalitis (inactivated): Neurologic events (encephalitis, encephalopathy, peripheral neuropathy) (1-2.3/106).
• Measles/MMR/MR: Febrile seizures (6-12 days, 3/103), Thrombocytopenia (15-35 days, 3/105), Anaphylaxis (0-1 hour, ~1/106), Encephalopathy (6-12 days, <<1/106).
• Oral poliomyelitis: VAPP (4-30 days, 2-4/106).
• Pertussis (DTwP): Persistent (>3 hours) inconsolable screaming (0-24 hours, <<1/100), Seizures (0-3 days, <<1/100), Hypotonic, hypo responsive episode (HHE) (0-48 hours, 1-2/103), Anaphylaxis(0-1 hour, 20/106), Encephalopathy (0-2 days, 0-1/106).
• Tetanus toxoid, DT: Brachial neuritis (2-28 days, 5-10/106), Anaphylaxis (0-1 hour, 1-6/106).
• Yellow fever: Vaccine-associated viscerotropic disease, 1/106.
• Varicella: Febrile seizures, 4-9/104.
• Reactions generally don't occur in already immune persons
• VAPP risk is higher after the first dose and for adults/immunocompromised individuals
• Most post-vaccination seizures are febrile and related to age.
• Although Encephalopathy is included as a rare reaction, causality is uncertain.
• Serious events that follow immunization are likely coincidental.