Brighton’s Classification for AEFI cases
S.No Valid Diagnosis / Case
definition
1 Abscess at injection site:
Abscess at injection site is a
localized soft tissue collection
of material, occurring at the site
of immunization
Levels of diagnostic certainty Window period
Level 1 of diagnostic certainty
A. Abscess of infectious etiology
• Spontaneous or surgical drainage of material from the
mass; AND
• Laboratory confirmation (Gram stain, culture or other tests) of microbiological
organisms with or without polymorphonuclear
leukocytes in material drained or aspirated from mass.
Abscesses of infectious etiology may be accompanied by
fever and/or regional lymphadenopathy.
B. Sterile abscess
• Spontaneous or surgical (see Footnote 3) drainage of material
from the mass;AND
• Material obtained from the mass prior to initiating antimicrobial
therapy, but with negative evaluation for infectious
etiology (which may include Gram stain, cultures or other
tests).
Sterile abscesses are typically not accompanied by fever and/or regional
lymphadenopathy
Level 2 of diagnostic certainty
In settings where laboratory evaluation for infectious etiology
(Gram stain, cultures, or other technique)was either not
performed, performed after starting antimicrobial therapy, or
not reported.
A. Abscess of infectious etiology
Spontaneous or surgical (see Footnote 3) drainage of
purulent6 material from the mass;
OR
• Collection of material diagnosed by an imaging technique
(e.g., sonogram, CT, MRI, or other modality) or
fluctuance7; AND
• Localized sign(s) of inflammation including at least one
of the following: erythema, pain to light touch, or warm to
touch at the injection site;
AND
• Resolution/improvement temporally related to antimicrobial
therapy.
Abscesses of infectious etiology may be accompanied by
fever (see Footnote 4) and/or regional lymphadenopathy.
B. Sterile abscess
• Spontaneous or surgical (see Footnote 3) drainage of
non-purulent (see Footnote 5) material from the mass;
OR
• Collection of material e.g., fluid diagnosed by imaging
technique (e.g., sonogram, CT, MRI, or other modality) or
fluctuance (see Footnote 6);
AND
• The absence of signs of local inflammation such as erythema,
pain to light touch, and warm to touch at the
injection site; OR
• No resolution/improvement temporally related to antimicrobial
therapy.
Sterile abscesses are typically not accompanied by fever (see
Footnote 4) and/or regional lymphadenopathy.
C. Type indeterminant: Insufficient information to determine
whether abscess is of infectious etiology or a
sterile abscess; i.e., report of incision and drainage of
the injection site mass but no culture results reported,
or report of the collection of material at the injection
site demonstrated by an imaging technique but clinical
symptoms or response to antimicrobial therapy not
reported.
Level 3 of diagnostic certainty

2 Anaphylaxis is a clinical
syndrome characterized by
• sudden onset AND
• rapid progression of signs and
symptoms AND
• involving multiple (≥2) organ
systems, as follows
Not applicable.
For all levels listed above, the following in and of themselves
do not constitute abscesses at the injection site: superficial vesicles or pustules on the
skin,
• suppurative lymph nodes adjacent to the site of immunization,
• septic joints adjacent to the site of immunization, or
• cellulitis and nodule at injection site
Level 1 of diagnostic certainty
• ≥1 major dermatological AND
• ≥1 major cardiovascular AND/OR ≥1 major respiratory criterion
Level 2 of diagnostic certainty
•≥1 major cardiovascular AND ≥1 major respiratory criterion
OR
• ≥1 major cardiovascular OR respiratory criterion AND
• ≥1 minor criterion involving ≥1 different system (other than cardiovascular or
respiratory systems) OR
• (≥1 major dermatologic) AND (≥1 minor cardiovascular AND/OR minor respiratory
criterion)
Level 3 of diagnostic certainty
• ≥1 minor cardiovascular OR respiratory criterion AND
• ≥1 minor criterion from each of ≥2 different systems/
Categories
Major criteria
Dermatologic or mucosal • generalized urticaria (hives) or
generalized erythema
• angioedema*, localized or generalized
• generalized pruritus with skin rash
Cardiovascular • measured hypotension
• clinical diagnosis of uncompensated
shock, indicated by the combination of
at least 3 of the following:
• tachycardia
• capillary refill time >3 s
• reduced central pulse volume
• decreased level of consciousness or
loss of consciousness
Respiratory • bilateral wheeze (bronchospasm)
• stridor
• upper airway swelling (lip, tongue,
throat, uvula, or larynx)
• respiratory distress—2 or more of the
following:
• tachypnoea
• increased use of accessory
respiratory muscles
(sternocleidomastoid, intercostals, etc.)
• recession
• cyanosis
• gruntingMinor criteria
dermatologic or mucosal • generalized pruritus without skin rash
• generalized prickle sensation
• localized injection site urticaria
• red and itchy eyes
Cardiovascular
• reduced peripheral circulation as indicated
by the combination of at least 2 of
• tachycardia and
• a capillary refill time of >3 s without
hypotension
• a decreased level of consciousness
Respiratory • persistent dry cough
• hoarse voice
• difficulty breathing without wheeze or
stridor
• sensation of throat closure
• sneezing, rhinorrhea

3 cellulitis at injection site
Cellulitis is defineda as an acute, infectiousb,
and expanding inflammatory
condition of the skin that is characterized by
the following inclusion and
exclusion criteria. Of note, cellulitis may be
accompanied by feverc and/or
regional lymphadenopathy, however, their
presence or absence does not
Gastrointestinal • diarrhoea
• abdominal pain
• nausea
• vomiting
Laboratory • Mast cell tryptase elevation > upper normal
limit
Level 1: Criteria as specified in the anaphylaxis case definition.
Level 2: Criteria as specified in the anaphylaxis case definition.
Level 3: Criteria as specified in the anaphylaxis case definition.
Event does not meet case definition
Additional categories for analysis
(4) Reported anaphylaxis with insufficient evidence to meet the case definition12.
(5) Not a case of anaphylaxis13.
(32) The interval between immunization and reported
anaphylaxis could be defined as the date/time of immunization
to the date/time of onset5 of the first symptoms
and/or signs consistent with the definition. If few cases
are reported, the concrete time course could be analyzed
for each; for a large number of cases, data can be
analyzed in the following increments:
Subjects with anaphylaxis by Interval to Presentation
Interval Number Percentage
<30 min after immunization
30≤60 min after immunization
60≤90 min after immunization
90≤120 min
Hourly increments thereafter
Level 1a of diagnostic certainty
At least three of the following four
signs/symptoms:
• Localized pain or tendernessd (pain to
touch);
• Erythemad;
• Indurationd or swellinge;
influence the level of diagnostic certainty. • Warmthd;
AND
• Reaction is at the injection sitef; AND
• Laboratory-confirmation by culture.g
If known,h exclusion criteria are:
• Spontaneous rapid resolutioni; AND/OR
• Fluctuance.j
OR
Level 1b of diagnostic certainty
• A diagnosis of cellulitis by a qualified
health care providerk;
THAT IS
• At the injection sitef; AND
• Laboratory-confirmation by cultureIf known,h exclusion criteria are:
• Spontaneous rapid resolutioni; AND/OR
• Fluctuance.j
Level 2 of diagnostic certainty
At least three of the following four
signs/symptoms:
• Localized pain or tendernessd (pain to
touch);
• Erythemad;
• Indurationd or swellinge;
• Warmthe;
AND
• Reaction is at the injection sitef; AND
• Has been diagnosed by a qualified health
care provider.g
If knownh, exclusion criteria are:
• Spontaneous rapid resolutioni; AND/OR
• Fluctuance.j
Level 3 of diagnostic certainty
At least three of the following four
signs/symptoms
• Localized pain or tendernessd (pain to
touch);
• Erythemad;
• Indurationd or swellinge;
• Warmthd;
AND
• Reaction is at the injection sitef; AND
• Has been reported by any person (not
specified as a qualified health care
providerg).
If known,h exclusion criteria are:
• Spontaneous rapid resolutioni; AND/OR
• Fluctuance.j