Transcript Document

Adverse Events
Following Immunization
Dr S.M.Zahraei
Center for Disease Control
Ministry of Health and Medical Education
600
100
90
80
70
60
50
40
30
20
10
0
400
300
200
100
0
19
84
19
85
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
NUMBER
500
CASE
COVERAGE
PERCENT
TREND OF DIPHTHERIA IMMUNIZATION
COVERAGE & CASES
(1984 –2003 , I.R.IRAN)
35
100
90
80
70
60
50
40
30
20
10
0
25
20
15
10
5
0
19
84
19
85
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
RATE/100000
30
CASE
COVERAGE
PERCENT
TREND OF PERTUSSIS IMMUNIZATION
COVERAGE & CASES
(1984 –2003,I.R.IRAN)
250
100
200
80
150
60
100
40
50
20
0
0
84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03
19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 20 20 20 20
CASE
COVERAGE
PERCENT
NUMBER
TREND OF NEONATAL TETANUS
IMMUNIZATION COVERAGE & CASES
(1984 –2003,I.R.IRAN)
100
90
80
70
60
50
40
30
20
10
0
80
RATE/100000
70
60
50
40
30
20
10
0
84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03
19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 20 20 20 20
INCIDENCE
COVERAGE
PERCENT
TREND OF MEASLES IMMUNIZATION
COVERAGE & CASES
(1984 –2003,I.R.IRAN)
100
100
80
80
60
60
40
40
20
20
0
0
84 985 986 987 988 989 990 991 992 993 994 995 996 997 998 999 000 001 002 003
9
1
1
1 1
1 1
1
1 1
1 1
1
1 1
1 1
2
2 2
2
CASE
COVERAGE
PERCENT
NUMBER
TREND OF POLIO IMMUNIZATION
COVERAGE & CASES
(1984 –2003,I.R.IRAN)
TREND OF BCG IMMUNIZATION
COVERAGE (1984 –2003,I.R.IRAN)
100
60
40
20
Year
20
00
20
01
20
02
20
03
99
98
97
96
95
94
93
92
91
90
89
88
87
0
84
Percent
80
Prevalence rate of H.B :
Survey 1991 : 3 %
Survey 1999 : 1. 7 %
20
03
20
02
20
01
20
00
19
99
19
98
19
97
19
96
19
95
100
90
80
70
60
50
40
30
20
10
0
19
94
PERCENT
TREND OF HEPATITIS B IMMUNIZATION
COVERAGE
(1994 –2003,I.R.IRAN)
AEFI is a medical incident that takes place
after an immunization, causes concern, and is
believed to be caused by immunization

Vaccine reaction
 caused by vaccine’s inherent properties

Programme error
 caused by error in vaccine preparation,
handling or administration

Coincidental


Injection reaction


happens after immunization but not
caused by it a
chance association
anxiety or pain of injection not vaccine
Unknown

cause can not be determined
Cluster of AEFI
>=2 cases of the same adverse event
following immunizations related in time,
geography or in the vaccine administered
– Why is it important to monitor for
clustering?
Potential Objectives For AEFI Surveillance
System
•
•
•
•
Detect, correct, and prevent programme errors
Identify problems with vaccine lots or brand
Prevent false blame from coincidental events
Maintain confidence by properly responding to
parent/community concerns while increasing
awareness (public and professional) about
vaccine risks
• Generate new hypotheses about vaccine
reactions that are specific to the
population
• Estimate rates of occurrence on AEFI in
the local population, compared with trial
and international data (particularly for
new vaccines being introduced)
DETECTING AND
REPORTING AEFIs
Which Events To Report?
• Death, hospitalization, or other severe/unusual
events
• Toxic shock syndrome
• Severe local reaction
• Sepsis
• Injection site abscess (bacterial/sterile)
• BCG lymphadenitis
• AEFIs causing concern or suspicion of vaccine
involvement
Which Reports To Investigate?
Investigate if
• possible programme error
• serious event of unexplained cause
• above expected rate (not just numbers)
• potential damage to the immunization
programme
Certain events (toxic shock syndrome, sepsis,
abscess,and BCG lymphadenitis) are likely to arise from
programme errors and must always be investigated
Programme Errors
• Non-sterile injection
– infection
• Incorrect preparation
– abscess (inadequate shaking)
– drug effect (use of drug instead of
vaccine/diluent)
• Injection in wrong site
– local reaction/abscess (wrong tissue
level)
– nerve damage
• Vaccine frozen
– local reaction
• Contraindication ignored
– avoidable severe reaction
Serious Events
• Anaphylactoid reaction (acute hypersensitivity reaction)
• Anaphylaxis
• Persistent (more than 3 hours) inconsolable screaming
• Hypotonic hyporesponsive episode
• Seizures, including febrile seizures
(6-12 days for measles/MMR; 0-2 days for DTP)
• Encephalopathy
(6-12 days for measles/MMR; 0-2 days for DTP)
Serious Events (cont…)
• Acute flaccid paralysis
– (4-30 days for OPV recipient; 4-75 days for contact)
• Brachial neuritis
– (2-28 days after tetanus containing vaccine)
• Thrombocytopaenia
– (15-35 days after measles/MMR)
• Disseminated BCG infection
• Osteitis/osteomyelitis
Contraindications
True contraindications are rare
• Current serious febrile illness
– delay vaccine administration
• History of severe AEFI after previous dose
• Evolving neurological disease
– avoid whole cell pertussis vaccine
– (e.g. uncontrolled epilepsy)
• Type 1 hypersensitivity to egg
- avoid yellow fever & influenza but can use vaccines
made in chick fibroblasts
• Symptomatic HIV
– avoid BCG and yellow fever
Contraindications
Adopted from Plotkin pg 66-67
Vaccine
Contraindication
All vaccines
Anaphylactic reaction to vaccine or
vaccine constituent
Severe febrile illness
DTP
Encephalopathy within 7 days of
administration
Immunodeficiency, or immunodeficient
household contact*
OPV
IPV
Anaphylactic reaction to neomicin,
streptomycin or polymyxin B
* Risk benefit assessment when administered to HIV positive individuals
Contraindications
Adopted from Plotkin pg 66-67
Vaccine
Contraindication
MMR
Anaphylaxis, pregnancy,
immunodeficiency*
None
Hib
Hepatitis B
Anaphylactic reaction to common
baker’s yeast
Yellow fever
Anaphylactic reaction to egg,
immunodeficiency
* Risk benefit assessment when administered to HIV-positive individuals
THANK YOU FOR
YOUR ATTENTION
Anaphylaxis
• Type 1 hypersensitivity reaction
• Circulatory failure
• Bronchospasm +/- laryngospasm/laryngeal oedema
– respiratory distress
• May include pruritis, flushing, angioedema, seizures,
vomiting, abdominal cramps & incontinence
• Occurs in previously sensitized individuals
Anaphylaxis
• Reported less from developing countries
– Less sensitization?
– Less reporting?
• Anaphylaxis is rare (1/1 000 000 vaccinations)
• Fainting is common
• Untrained staff may misdiagnose fainting/dizziness
for anaphylaxis or vice versa
• Administration of adrenaline in a faint may be
dangerous
PROMPT MANAGEMENT IS VITAL!
Seizures
• Particularly associated with measles and DTP
vaccination (pertussis component)
– febrile seizures Temp >38
– afebrile seizures Temp normal
• Febrile seizures more common with pertussis
• An association with non-febrile seizures has not
been proven
Adverse Reactions To BCG
Disseminated BCGits
– widespread infection, 1-12 months after BCG
– usually in immunocompromised individual
– confirm by isolation of Mycobacterium bovis
BCG strain
– treat with antituberculous regimen including
Rifampicin and Isoniazid
Osteitis/osteomyelitis
– infection of the bone with M bovis BCG strain
– management as above
Adverse Reactions To BCG
Suppurative lymphadenitis
occurs within 2-6 months of BCG vaccination
Case Definition
• 1 lymph node> 1.5 cm in size/draining sinus
over a lymph node
• usually occurs in the axilla, on the same side as
innoculation
Management
heals spontaneously over months
only treat if sticking to skin or draining
surgical drainage and local installation of
antituberculous drug
systemic Rx is ineffective
____________
____________
____________
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Tetanus Vaccine
Brachial neuritis
• Presents with pain in shoulder and upper arm
• Followed by weakness +/- wasting of arm and
shoulder muscles
• Sensory loss not prominent
• Occurs 2-28 days after vaccination
• Possibly a manifestation of immune complex
disease
• Management is symptomatic
Encephalopathy And Encephalitis
Possibly associated with measles & pertussis vaccine
• Case definition of encephalopathy
– 2 out of 3 of
• seizures
• alteration of consciousness lasting for one day or
more
• distinct change in behavior for one day or more
• Temporal relationship
– within 48 hrs with DTP
– within 7-12 days after measles or MMR
Encephalitis And Measles Vaccination
• An analysis of claims for encephalitis
following measles vaccine in the USA found
clustering of events 8-9 days after vaccination
(Wetbel 1998, Duclos 1998)
• This supports, but does not prove, the
possibility that measles vaccine was causative
• Risk is less than 1 case per million
Hypotonic Hypotesive Episode
• Mainly associated with DTP
– Case definition
• Event of sudden onset occurring within 48
(usually less than 12) hours of vaccination
and lasting from one minute to several hours
• In a child < 10 years of age
• ALL of the following must be present
– limpness (hypotonic)
– reduced responsiveness
– pallor or cyanosis - or failure to observe/recall
• Transient, self-limiting, NOT a contraindication to
further vaccination
Acute Flaccid Paralysis
Vaccine associated paralytic poliomyelitis
• Occurs within 4-30 days of receipt of OPV or 4-75
days after contact with vaccine recipient
Case
Following a national immunization day in 1996, cases of
paralysis were reported after receiving OPV. On
laboratory analysis, the wild virus was found, showing
that the children had been infected with wild poliovirus
before immunization. The cases of poliovirus were
coincidental, and not caused by the vaccine.
Unproven Associations
And Public Concerns
•
•
•
•
•
•
•
•
•
•
Influenza vaccine and Guillaine Barré Syndrome
MMR and autism, Crohn’s disease
Polio and HIV
Hepatitis B and multiple sclerosis
DTP and permanent brain damage
DTP and increased risk of mortality
Aluminium and macrophagic myofasciitis
Bovine spongiform encephalopathy (BSE)
Thiomerosal
Multiple vaccines given simultaneously
Common, more reactions
Vaccine
Local reaction
(pain, swelling, redness)
Fever >38C Irritability, malaise &
systemic symptoms
BCG
90-95%
-
-
Hib
5-15%
2-10%
-
-
1-6%
5-15%
5% rash
<1%
<1%**
~10%*
~10%
~25%
Up to 50%
Up to 50%
Up to 55%
HepB
Adults: 15%; Children: 5%
Measles/
~10%
MMR
Polio
(OPV)
Tetanus
DTP
(pertussis)
* Rate of local reactions likely to increase with booster doses, up to 50-85%
** Symptoms include diarrhoea, headache, and/or muscle pains
Rare, more frequent reactions
Vaccine
Reaction
Onset
interval
Rate per million
doses
BCG
Suppurative lymphadenitis
BCG osteitis
Disseminated BCG
2-6 months
1-12 months
1-12 months
100-1000
1-700
2
Hib
Nil known
Hep B
Anaphylaxis
Guillain Barré syndrome
0-1 hour
1-6 weeks
1-2
5
Measles
/MMR
Febrile seizures
Thrombocytopaenia
Anaphylaxis
5-12 days
15-35 days
0-1 hour
333
33
1-50
OPV
Vaccine-associated paralytic 4-30 days
poliomyelitis (VAPP)
Risk is higher for first dose, adults,
and immunocompromised
0.76-1.3 (1st dose)
0.17 (subsequent
doses)
0.15 (contacts)
Rare, more frequent reactions
Vaccine
Reaction
Onset
interval
Rate per
million doses
Tetanus
Brachial neuritis
Anaphylaxis
Sterile abscess
2-28 days
0-1 hour
1-6 weeks
5-10
1-6
6-10
0-24 hours
1000-60 000
0-3 days
0-24 hours
570
570
0-1 hour
0-3 days
20
0-1
Tetanus-diphtheria Nil extra to tetanus
DTP
reactions
Persistent (>3 hrs)
inconsolable screaming
Seizures
Hypotonic,
hyporesponsive episode
(HHE)
Anaphylaxis/shock
Encephalopathy
Rare,more frequent reactions
Vaccine
Reaction
Onset interval
Rate per million
doses
Japanese
encephalitis
Serious allergic reaction
10-1000
Neurological event
1-2.3
Yellow fever
Post-vaccination
Encephalitis
7-21 days
Allergic
reaction/anaphylaxis
0-1 hours
500-4000 in
infants<6
months
5-20
CASE STUDIES
An outbreak of lymphadenitis three months after BCG
immunization was traced to a switch to a different strain of vaccine.
The investigation also highlighted a number of programme errors
(vaccines not properly reconstituted, and injections not given
intradermally).
Cause: Vaccine reaction compounded by programme errors
A one-year-old child died within 12 hours of receiving measles
vaccine. It was reported as a possible anaphylaxis because of its
rapid onset. Investigation found that the vaccine used was likely to
have been reconstituted one day prior to this particular use.
Cause: Non-sterile injection, not anaphylaxis
CASE STUDY
Four children died and a fifth was hospitalized after
receiving measles vaccine from the same vial.
Vaccine was not refrigerated, and was transported
house to house for immunization. Reactions began
four to five hours after vaccination, with vomiting,
unconsciousness, and meningeal irritation. S. aureus
was cultivated from the incriminated vial.
Cause: Non-sterile injection
Turkey
Programmatic
error
India
Algeria
Yemen
1997
Insulin given to 70 infants instead of DTP
vaccine with 21 deaths
TT
DTP
Insulin
vial
Vaccine vials