Causality assessment of AEFI's

Detection and reporting of AEFI

Parents of immunized infants/children, health workers at immunization facilities and staff of accident and emergency rooms in hospitals are most likely to recognize or detect AEFIs when they first occur.

Reportable AEFIs:

Serious AEFIs
Signals and events associated with a newly introduced vaccine
AEFI’s caused because of immunisation errors
Significant events of unexplained cause occurring within 30 days of vaccination
Events causing significant parental/community concern
Injection site reactions lasting for more than 3 days

AEFI investigation

Some AEFI reports will need further investigation. The purpose of an AEFI investigation is to:

Confirm the diagnosis (or propose other diagnoses) and determine the outcome of the adverse event,
Identify specifications of implicated vaccine(s) used to immunize patient(s),
Examine operational aspects of the immunization programme, which may have led to immunization errors,
Justify the search for other AEFI cases/clustering,
Compare background risk of adverse event (occurring in unimmunized people) to the reported rate in the vaccinated population.

Reported events requiring the initiation of an investigation are:

Serious AEFIs, i.e. adverse events or reactions that result in death, hospitalization (or prolongation of existing hospital stay), persistent or significant disability or incapacity (e.g. paralysis), or are potentially life-threatening,
Clusters of minor AEFIs (Two or more instances of an event related in time, place, population subgroup, or common exposure (e.g., vaccine). AEFI clusters are usually associated with a particular provider, health facility, and/or a vial of vaccine that has been inappropriately prepared or contaminated).
Signals and events associated with newly introduced vaccines,
Other AEFIs as recommended by WHO:
- AEFIs that may have been caused by immunization error (e.g. bacterial abscess, severe local reaction, high fever or sepsis, BCG lymphadenitis, toxic shock syndrome, clusters of AEFIs),
- Significant events of unexplained cause occurring within 30 days after a vaccination,
- Events causing significant parental or community concern.

CAUSALITY ASSESSMENT OF AEFI’s

Causality assessment is the systematic review of data about an AEFI case; it aims to determine the likelihood of a causal association between the event and the vaccine(s) received. For individual cases, one tries to apply the evidence available on the basis of the history and time frame of the event to arrive at a causal likelihood. The quality of the causality assessment depends upon:

the performance of the AEFI reporting system in terms of responsiveness, effectiveness and quality of investigation and reports;
the availability of adequate medical and laboratory services and access to background information;
the quality of the causality review process.

Considerations for assessing individual case causality of AEFI:

Temporal relationship: The vaccine exposure must precede the occurrence of the event.
Definitive proof that the vaccine caused the event: Clinical or laboratory proof that the vaccine caused the event is most often found for live attenuated vaccines.
Population-based evidence for causality – i.e. what is known about “Can it?”
1. A definitive “yes” at the population level is consistent with causality at the individual level.
2. A strong “no” at the population level is inconsistent with causality at the individual level.
3. If there is no clear answer to the question at the population level, this will often lead to an indeterminate conclusion at the individual level. If there are significant numbers of individual cases, however, this clearly points to the need to try to answer the question at the population level.
Biological plausibility: In situations where the “Can it?” question has no clear “yes” or “no” answer, biological plausibility may provide support for or against vaccine causality. In other words, the association should be compatible with existing theory and knowledge related to how the vaccine works.
Consideration of alternative explanations: In doing causality assessment on an individual case report, it must be remembered that in essence one is conducting a differential diagnosis. Thus it is important to consider “coincidental AEFI” – i.e. an AEFI due to something other than the vaccine product, immunization error or immunization anxiety. All reasonable alternative etiological explanations should be considered, including:

pre-existing illness;
newly acquired illness;
spontaneous occurrence of an event without known risk factors;
emergence of a genetically programmed disease;
other exposures to drugs or toxins prior to the event;
surgical or other trauma that leads to a complication;
a manifestation of, or complication of, a coincidental infection that was present
before or at the time of immunization, or was incubating, but was not apparent at the time of immunization.

6. Prior evidence that the vaccine in question could cause a similar event in the vaccine. The concept of “rechallenge”, which is more commonly used in the assessment of causality in medicines, has been helpful for certain vaccine event considerations

Steps for causality assessment of an individual AEFI

Causality assessment has four steps, as follows: If multiple vaccines are given simultaneously, the reviewers will have to assess causality separately for each suspected vaccine.

Step 1: Eligibility – The first step aims to determine if the AEFI case satisfies the minimum criteria for causality assessment.
Step 2: Checklist – The second step involves systematically reviewing the relevant and available information to address possible causal aspects of the AEFI.
Step 3: Algorithm – The third step obtains a trend as to the causality with the information gathered in the checklist.
Step 4: Classification – The fourth step categorizes the AEFI’s association to the vaccine or vaccination on the basis of the trend determined in the algorithm.

Eligibility for causality assessment: