Basic concepts of vaccines

&
Adverse Events Following Immunization (AEFI)

September 20/2021
Adama Town
Kassech Sintayehu
 Learning Objectives
At the end of this session participants will be
able to:
• Identify the different components of vaccines
• List down the different types of vaccines
• Define pharmacovigilance
• Identify the rational for vaccine
pharmacovigilance
• Define Adverse events following Immunization
(AEFI)
• Identify the different categories of AEFI
A: Adverse
E: Effects/Events
F: Following
I : Immunization
 Components of vaccines
• Monovalent eg • eg Aluminium
measles salts
• Multivalent eg
DTaP-HepB-Hib

Antigens Adjuvants

Vaccines
Preservatives
Antibiotics
& Stabilisers

• eg Thiomersal • eg Neomycin
preservative
• Eg albumin
stabiliser
 Classification
Live attenuated vaccines (LAV)

• Bacteria:
• BCG vaccine
• Virus:
• Live Japanese encephalitis vaccine, oral poliovirus vaccine,
measles vaccine, mumps vaccine, rotavirus vaccine, rubella
vaccine, yellow fever vaccine

Inactivated (killed antigen) vaccines

• Bacteria:
• Whole -cell pertussis (wP)
• Virus:
• Inactivated Japanese encephalitis vaccine, inactivated
poliovirus vaccine (IPV)
 Classification (contd)
Subunit vaccines (purified antigens)

• Protein-based:
• Hepatitis B vaccine
• Acellular pertussis vaccine(aP)
• Polysaccharide:
• Meningococcal polysaccharide vaccine
• Pneumococcal polysaccharide vaccine
• Typhoid Vi polysaccharide vaccine
• Conjugate vaccine:
• Haemophilus influenzae type b (Hib) conjugate vaccine, meningitis A and B
conjugate vaccine
• Pneumococcal conjugate vaccines (PCV-7, PCV-10, PCV-13)
• Vi(typhoid) conjugate vaccine

Toxoids

• Tetanus toxoid
• Diphtheria toxoid
 Differences between vaccines and other
drugs: Relevance to pharmacovigilance

Vaccines Other Drugs

• Prevention in healthy, • Treatment in ill,
larger population smaller population
− Lower risk tolerance − More tolerant of risk
• Limited number of • Large number of products,
products many classes
• With single dose, greater • Treatment over time: less
potential for temporal “coincidence”
“coincidence” after a single dose
 vaccines and other drugs Cont’
Vaccines
• Prone to “program error”
• Injection “reaction”
• Cold chain often critical
• Biological product − more
prone to lot variation and
instability
Other Drugs
• Less prone to
administration error
• Less prone to
administration “reaction”
• Storage/handling less
critical
• Chemical product
 vaccines and other drugs Cont’

Vaccines Other Drugs

• Mass campaigns: many
• No mass campaigns −
doses in short time,
“private” prescribing to
defined population
less defined population
• Politics of access/safety
• Politics of access/safety
− Collaboration between
− Less relationship between
public health/NIP, NRA and
health system/govt/NRA
manufacturers
and manufacturers

Hence for vaccine demand higher safety and more careful

quality standards and monitoring.
 Contraindications and precautions to
vaccination

A contraindication to vaccination is a
rare characteristic in a recipient that Do not
increases the risk of a serious adverse vaccinate
reaction if the vaccine is given. E.g.
previous H/o anaphylaxis

Precautions, in contrast, are events or

Vaccinate conditions that should be considered in
with determining if the benefits of the
caution vaccine outweigh the risks (especially if
the would-be recipient is
immunocompromised or pregnant).
 Pharmacovigilance & vaccine pharmacovigilance

Pharmacovigilance
Science and activities Vaccine
Any untoward medical
relating to the Pharmacovigilance
occurrence that at any dose:

detection, assessment, Vaccine pharmacovigilance* the

understanding
and prevention of adverse
effects or any other drug-
related problems.
science and activities relating to
the detection, assessment,
understanding and communication
of AEFI and other vaccine- or
immunization-related issues, and
to the prevention of untoward
effects of the vaccine or
immunization.

* Report of CIOMS/WHO Working Group on Vaccine Pharmacovigilance, 2012

 Special need for vaccine pharmacovigilance

Universal vaccination is recommended / mandated.

Risk-benefit ratio for vaccines is different from

drugs.

Pre-licensure safety data are not enough to

assess the complete safety profile of a vaccine.

• New vaccines may be rapidly demanded

to combat a new (e.g., epidemic or pandemic) disease.
 Pre-licensure assessment of vaccine
safety
Adverse Reactions
detection
Sample size Common Rare

Animal trials +/− −

Clinical trials
Phase I 10-100 +/− −
Phase II 100-1,000 + −
Phase III 1,000-10,000 + −
– (negative sign) shows : Does not detect adverse reactions which are:
• rare, delayed, unexpected
• occur in sub-populations
• with vaccine combinations
 Definition of AEFI
…any untoward
medical occurrence
which follows
immunization and
which does not Symptom
necessarily have a
causal relationship with
the usage of the
vaccine.
Sign

The adverse event

may be any Lab
unfavorable or Finding
unintended sign,
abnormal laboratory
finding, symptom or Disease
disease.
 AEFI Frequency Terminology
Frequency category Frequency in rate Frequency in %

Very common* > 1/10 > 10%

Common > 1/100 and < 1/10 > 1% and < 10%
(frequent)

Uncommon > 1/1,000 and < 1/100 > 0.1% and < 1 %
(infrequent)

Rare > 1/10,000 and < 1/1,000 > 0.01% and < 0.1%

Very rare* < 1/10,000 < 0.01%

Source: Council for International Organizations of Medical Sciences (CIOMS), 1995 * Optional categories
CIOMS/ WHO cause specific definition of AEFIs

An AEFI that is
caused or
1 2
precipitated by 4 5
3 An AEFI that is
AnVaccine
AEFI that is Vaccine
a vaccine that Immunization
Immunization
caused by
product-
caused or isquality
due to one An AEFI that is anxiety-
precipitated error-related An AEFI arising something
Coincidental
related by or more
defect-related caused by related other than the
a vaccine due quality defects reaction
Inappropriate from anxiety event
toreaction ofreaction reaction
about the vaccine
one or more the vaccine vaccine
immunization. product,
of the inherent product handling,
immunization
properties of including its prescribing or
error or
the vaccine administration administration.
immunization
product. device as
anxiety
provided by
the
manufacturer.
 CIOMS/ WHO cause specific definition of AEFIs

1 EXAMPLE
2 4
3 5
Vaccine Vaccine
Failure by the Immunization EXAMPLE
manufacturer Immunization A fever after
product- quality defect- EXAMPLE anxiety-
EXAMPLE
EXAMPLE torelated
completely error-related Coincidental
vaccination
related Transmission related
Vasovagal
Extensive inactivate reaction (temporal
event
reaction
limb swelling reaction a of infection by reaction
syncope in an association)
lot of
following DTP contaminated adolescent and malarial
inactivated
vaccination. multidose following parasite
polio vaccine
vial. vaccination. isolated from
leads to cases
of paralytic blood.
polio.

Examples
 Vaccine reactions

1 2 3 4 5
Vaccine Vaccine quality Immunization Immunization
Coincidental
product-related defect-related error-related anxiety-related
event
reaction reaction reaction reaction

EXAMPLE EXAMPLE MINOR REACTIONS

Extensive Failure by the
limb swelling manufacturer
following DTP to completely
vaccination. inactivate a lot SEVERE REACTIONS
of inactivated
polio vaccine
leads to cases
of paralytic
polio.
 Vaccine reactions 1 2
Vaccine Vaccine quality
product-related defect-related
reaction reaction

MINOR REACTIONS SEVERE REACTIONS

 Usually occur within a few hours of injection.

 Resolve after short period of time and pose little danger.
 Local (includes pain, swelling or redness at the site of
injection).
 Systemic (includes fever, malaise, muscle pain,
headache or loss of appetite).
 MINOR REACTIONS SEVERE REACTIONS
Minor vaccine reactions, treatments and rates associated with childhood vaccines
Local reactions Systemic reactions
Vaccine Irritability, malaise and
(pain, swelling, redness) Fever > 38°C systemic symptoms
BCG 90% – 95% – –

Adults up to 15%, Children up to

Hepatitis B 1 – 6% –
5%

Hib 5 – 15% 2% – 10%

Measles/MR/MMR ~ 10% 5% – 15% 5% (Rash)

OPV None Less than 1% Less than 1%

Pertussis (DTwP) up to 50% up to 50% up to 55%

Pnemucoccal
~ 20% ~ 20% ~ 20%
conjugate5

Tetanus/DT/aTd ~ 10%4 ~ 10% ~ 25

Treatment • Cold cloth at injection site • Give extra oral fluids • Give extra oral fluids
• Paracetamol • Wear cool clothing • Paracetamol
• Tepid sponge or bath
• Paracetamol
 Vaccine reactions 1 2
Vaccine Vaccine quality
product-related defect-related
reaction reaction

MINOR REACTIONS SEVERE REACTIONS

 Usually do not result in long-term problems.

 Can be disabling.
 Are rarely life threatening.
 Include seizures and allergic reactions caused by the
body's reaction to a particular component in a
vaccine.
 Vaccine reactions Vaccine
1
product-related
reaction
2
Vaccine quality
defect-related
reaction

MINOR REACTIONS SEVERE REACTIONS

Severe vaccine reactions, treatments and rates associated with childhood vaccines
Frequency per
Vaccine Reaction* Onset interval
doses given
BCG Fatal dissemination of BCG infection 1 – 12 months 0.19 – 1.56/1.000.000
Vaccine associated paralytic
OPV 4 – 30 days 2 – 4/1.000.000
poliomyelitis (VAPP)**
Prolonged crying and seizures*** 0 – 24 hours < 1/100
DTwP
HHE 0 – 24 hours < 1/1.000 – 2/1.000

Febrile seizures 6 – 12 days 1/3.000

Measles Thrombocytopenia 15 – 35 days 1/30.000

Anaphylaxis 1 hour 1/100.000

* Reactions
* Reactions
(except
(except
anaphylaxis)
anaphylaxis)
do notdooccur
not occur
if already
if already
immune
immune
(90%(90%
of those
of those
receiving
receiving
a second
a second
dose);dose);
children
children
>6 years
>6 years
unlikely
unlikely
to have
to have
febrile
febrile
seizures.
seizures.
** VAPP
** VAPP
risk higher
risk higher
for first
for dose
first dose
(1 in (1
750in 000
750 compared
000 compared with 1
with
in 5.1
1 inmillion
5.1 million
for subsequent
for subsequent
doses),
doses),
and for
andadults
for adults
and immunocompromised
and immunocompromised clients.
clients.
*** Seizures
*** Seizures
are mostly
are mostly
febrile.
febrile.
The risk
The ofrisk
having
of having
a seizure
a seizure
depends
depends
on theonpersons
the persons
age. age.
The risk
The isrisk
much
is much
lowerlower
in infants
in infants
<4 months
<4 months
of age.
of age.
 Difference between serious and severe reactions

Severe reactions
(Not regulatory term)

• Can be disabling and, rarely,

life threatening. Serious
Any untoward reactions
medical occurrence that
• Must be reported. (Regulatory term)
at any dose:
• Most do not lead to long-term
problems.
• Severe reactions include Results in death.
serious reactions but also Requires inpatient
include other severe reactions. hospitalization.
Results in persistent or
significant disability.
Is life-threatening.
Congenital Anomaly
Immunization error-related reactions
Error in vaccine handling:
• Exposure to excess heat or cold as a result of inappropriate transport, storage or handling of the
vaccine (and its diluents where applicable)
• Use of a product after the expiry date

Preventable AEFI
Error in vaccine prescribing or non-
adherence to recommendations for use
• Failure to adhere to a contraindication
• Failure to adhere to vaccine indications or prescription (dose or schedule)

Error in administration
• Use of an incorrect diluent or injection of a product other than the intended vaccine
• Incorrect sterile technique or inappropriate procedure with a multidose vial
 Immunization Errors
Immunization error Related reaction
Error in Exposure to excess heat, Systemic or local reactions due to
vaccine storage or handling of the changes in the physical nature of the
handling vaccine (and its diluents where vaccine
applicable)
Use of a product after the Loss of potency and failure of protection
expiry date
Error in Failure to adhere to a Anaphylaxis, disseminated infection
vaccine contraindication with a LAV e.g. Disseminated BCG
prescribin Failure to adhere to vaccine Systemic and/or local reactions,
g indications or prescription neurological, muscular, vascular or bony
(dose or schedule) injury due to incorrect injection site,
equipment or technique
Error in Use of an incorrect diluent or Failure to vaccinate due to incorrect
administra injection of a product other diluent, reaction due to inherent
tion than the intended vaccine properties of whatever was administered
other than the intended vaccine or
diluent
Incorrect sterile technique or Infection at/beyond the site of injection
inappropriate procedure with a
multi-dose vial
How can you prevent immunization error-
related AEFI?
• Do not store and/or pack other diluents or medications
together with the vaccine.
• Always check the labels of vaccines and diluents before
reconstitution – vaccines and diluents should be from the
same manufacturer.
• Follow manufacturer’s recommendations on storage,
vaccine preparation, route and technique of
administration, and contraindications and precautions.
• Draw the auto-disable (AD) syringe just before
vaccination.
• Do not touch the needle.
 How can you prevent immunization
error-related AEFI?
• Do not touch the rubber cap of the vaccine
vial.
• If reconstituted, never carry vaccines from one
place to another.
• Discard the vaccine if it was reconstituted
before the maximum recommended time or at
the end of the session, whichever comes first.
• When in doubt, contact your supervisor for
clarification. Do not hesitate to report issues
or concerns when identified.
 |
28
0 Immunization anxiety-related
reaction:
4 arising from anxiety about the
immunization and fear of injection

What are
immunization o Different factors can contribute to
anxiety-related anxiety-related reactions such as
different vaccination environment,
reactions? novelty of the vaccine, fear of
injection.
o To help prevent fainting and
injures that could occur from a
fall, vaccinated individuals should
stay seated for about 15 minutes
after vaccination.

https://www.who.int/vaccine_safety/publications/aefi
_surveillance/en/
https://www.who.int/publications/i/item/978-92-4-151594-8
Immunization anxiety-related reactions

Potential vaccines can become stressed and may

react in anticipation to, and as a result of, any kind
of injection. This reaction is unrelated to the
constituents of the vaccine product-
• Fainting (vasovagal syncope or syncope)
• Hyperventilation
• Breath-holding and vomiting
• Screaming
• Needle phobia
• Mass hysteria
 |
30
0 Coincidental event:
event that happens after vaccination
5 but is not caused by vaccine or
vaccination process
What are
coincidental o Adult and elderly populations
events? with chronic diseases may
develop conditions irrespective of
vaccination that may be
attributed to vaccine.
o Similar events may occur in
healthy individuals where higher
frequency of a specific condition,
including any communicable
disease, can be expected based
on age, sex, geographic location
or ethnic background.
https://www.who.int/vaccine_safety/publications/aefi
_surveillance/en/
 Coincidental events
An event may occur coincidentally with immunization and sometimes be falsely
attributed to the vaccine i.e. a chance temporal association is falsely attributed to
immunization.

• Many events, including deaths (eg SIDS) can be falsely attributed to vaccine through
a chance association.

Inevitable especially visible in a mass immunization campaign.

Vaccines are normally administered early in life when infections , illnesses,

emergence of underlying congenital conditions.
 Key AEFI terminology: Signal
Prev
iousl
y
unk
now
Reported n
Or
information on Inco
possible causal mpl
Usually
more than
etel
a single
report
relationship y
required

docu
between an men
adverse event ted
and vaccine Important considerations
•seriousness of the event

•quality of the information.

Source: WHO International Drug Monitoring Programme, 1991

 Key AEFI terminology: Cluster

Aggregation of relatively
uncommon events or diseases
"A cluster of AEFIs
is two or more
in space and/or time in
cases of the same
adverse event
frequency that are believed or
related in time,
place or vaccine
perceived to be greater than
administered".*
could be expected by chance.**

* WHO Aide Memoire: AEFI Investigation, 2004

** Last, John M. 2001. A Dictionary of Epidemiology, 4th ed,
 Key messages
Vaccines are classified into different types based on their nature

• Severe AEFIs are categorized as serious if it results in death, requires inpatient hospitalization, results
in persistent or significant disability, is life-threatening or causes congenital anomaly

There are several components in vaccines and any one of them can cause AEFI

• Immunization error is a cause that is preventable

• Coincidental and other causes should be ruled out before attributing the AEFI to the vaccine itself

AEFI can be minor and severe

There are 5 broad causes of AEFI

Thank you !