Adverse event following immunization (AEFI): any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the use of the vaccine. The adverse event may be any unfavourable or unintended sign, abnormal laboratory finding, symptom or disease.
An AEFI that is caused or precipitated by a vaccine due to one or more of the inherent properties of the vaccine product is called vaccine product-related & Vaccine quality defect-related reactions.
Vaccines are designed to induce a response by the immune system which involves a complex interaction between the vaccine antigens, the adjuvant (if present), antigen-presenting cells, lymphocytes and multiple immune mediators (cytokines). This interaction is important to the development of the desired immunity against the specific vaccine-preventable disease.
However, the immune response in a vaccine may manifest as relatively common and mild adverse reactions to the vaccine, such as injection site redness and swelling or fever. Homeostatic mechanisms usually limit the inflammatory response, so that such reactions are short-lived and have no lasting consequence. Uncommonly, the immune response to one or more vaccine components may result in a longer-lasting and more severe adverse reaction. Rarely, the immune response may cause a life-threatening allergic reaction.
It is important to note that vaccine product-related reactions may unmask a predisposition to other adverse events in certain high-risk individuals that would not occur in the majority of vaccines.
For example, fever is a relatively common inflammatory response following vaccination. For most vaccines the fever is of short duration and there are no associated adverse reactions. However, in children with an underlying seizure disorder, or in infants and toddlers with a tendency to have febrile seizures the fever may trigger a seizure. Other events that cause fever, like respiratory infection, could also trigger a seizure. In such cases, the seizures result as a combination of an inherent property of the vaccine that caused fever and underlying factors in the vaccine that lowered the threshold for seizure associated with fever.
Types of Vaccine product-related & Vaccine quality defect-related reactions:
- Reaction associated with the route and/or site of administration of the vaccine product or vaccine specific characteristics. Ex; Pain at the time of injection and associated physiologic responses.
2. Immune-mediated vaccine reactions:
a. Local reaction, with involvement of injection site, due to one or more vaccine components.
- Example: Extensive limb swelling post-DTP vaccination
- Granulomatous inflammation at the injection site with or without regional lymphadenitis (most commonly re- lated to BCG vaccine)
b. Multisystem (generalized) reaction due to one or more vaccine components
- Examples:
- (i) Systemic inflammatory response, e.g. fever or lethargy
- (ii) Mast cell degranulation (IgE mediated hypersensitivity (anaphylaxis) and Non-IgE mediated hypersensitivity (reactions in this group are commonly referred to as anaphylactoid reactions )
- (iii) Disseminated granulomatous reaction, e.g. disseminated BCG in immunodeficient hosts
- (iv) Immune complex mediated reaction (Serum Sickness Reaction).
c. Organ-specific reaction due to one or more vaccine components
- Example: Auto-immune or undefined mechanism (CNS e.g. demyelinating conditions such as GBS post-influenza vaccination, Blood e.g. thrombocytopenia post-MMR vaccination, Skin e.g. rashes after vaccination, including urticaria
3. Consequence of replication of vaccine-associated microbial agent(s) in the vaccine or a close contact of the vaccine. The microbial agent(s) could be:
- Attenuated vaccine agent.
- Wild type vaccine agent due to insufficient inactivation during the manufacturing process.
- Contaminant introduced into vaccine during the manufacturing process.
4. Direct toxic effect of vaccine component or contaminant (e.g. qual- ity defect).
Case study: Vaccine product-related AEFI
A 19 month old infant presents with marked leg swelling, pain and inability to walk within 6 hours of receiving booster vaccinations
Patient History:
- Infant was a healthy 19 month old female who developed marked right thigh swelling, redness and pain within 6 hours of receiving booster vaccinations.
- At the visit to the clinic she received a booster dose of diphtheria, pertussis and tetanus in her right thigh, a booster dose of conjugated Haemophilus vaccine in the left thigh and trivalent oral polio vaccine administered by mouth.
- She had received her primary immunisation series at 6, 10 and 14 weeks of age, consisting of trivalent oral polio vaccine administered by mouth, hepatitis B virus vaccine, Haemophilus vaccine and diphtheria, pertussis and tetanus vaccine.
- No prior adverse reactions had been noted.
- No childhood or other illnesses noted.
Differential Diagnosis
- administration error pyomyositis hypersensitivity reaction
- generalised swelling reactions localised abscess
- extensive limb swelling (ELS) idiopathic
Examination
Vitals:
Temperature: 38.5 ̊C
Respiratory rate, blood pressure and heart rate: nil of note
Clinical Findings:
Marked swelling of the right thigh, with redness and tenderness No discernable swelling noted in the left thigh
No generalised oedema
Investigations
- Ultrasound examinations demonstrated swelling of both the subcutaneous and muscle layers of the vaccinated leg.
- Repeat ultrasound examination after 48 hours showed considerable resolution of muscle swelling, compared with subcutaneous tissue swelling.
- Although ultrasound is not typically done, it performed to rule out localised abscess formation.
Actual diagnosis:
An Arthus reaction (type III hypersensitivity reaction) which occurs rarely after vaccination but can occur after tetanus toxoid–containing or diphtheria toxoid–containing vaccines.
Arthus reaction
The Arthus reaction was discovered by Nicolas Maurice Arthus in 1903 when he repeatedly injected horse serum subcutaneously into rabbits. He found that after four injections oedema developed at the injection site causing the serum to be absorbed slowly. Further injections resulted in the development of gangrene.
Arthus reactions, although fairly rare, are reported after patients receive vaccinations against diphtheria and tetanus. Where they develop a local vasculitis associated with deposition of immune complexes and activation of complement. Immune complexes form in the setting of high local concentration of vaccine antigens and high circulating antibody concentration. These reactions are characterised by severe pain, swelling, induration, edema, hemorrhage, and occasionally necrosis. This is a form of local type III hypersensitivity reaction occurring in a previously sensitized person, with signs and symptoms typically occurring 4–12 hours after vaccination.
Treatment
A dose of acetaminophen was given every 4 hours for 24 hours for pain and the child was observed at home. No further interventions were required.
Final Outcome
Fever defervesced within 12 hours. Limb oedema and tenderness resolved gradually over the following two days, and the child resumed increasingly full use of the affected limb as the other clinical signs resolved. Within a week she had made a full recovery.
References:
CIOMS/WHO Working Group on Vaccine Pharmacovigilance report
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