PRINCIPLES OF EPIDEMIOLOGY AND EPIDEMIOLOGIC METHODS

manufacturer with the vaccine, since the diluent is Reading the Stages of the WM
specifically designed for the needs of that vaccine, with Stage 1. The inner square is lighter than the outer circle. If
respect to volume, pH level and chemical properties. the expiry date has not been passed .: USE the
Store the diluents, between +2° to + 8° C in the ILR. If vaccine
there are constraints of space, then store diluents outside Stage 2. The inner square is still lighter than the outer
the cold chain. However, remember to cool diluents for at circle. If the expiry date has not been passed :
least 24 hours before use to ensure that vaccines and USE the vaccine
diluents are at to +8°C when being reconstituted.
Otherwise, it can lead to thermal shock i.e. the death of Discard Point :
some or all the essential live organisms in the vaccine. Store Stage 3. The colour of the inner square matches that of the
the diluents and droppers with the vaccines in the vaccine outer circle : DO NOT use the vaccine
carrier during transportation. Diluents should not come in
direct contact with the ice pack. Beyond the Discard Point
Stage 4. The colour of the inner square is darker than the
The Vaccine Vial Monitor (VVM) (130, 131) outer circle : DO NOT use the vaccine
A VVM is a label containing a heat-sensitive material The VVM does not directly measure vaccine potency but
which is placed on a vaccine vial to register cumulative heat it gives information about the main factor that affects
exposure over time. potency i.e. heat exposure over a period of time.
The combined effects of time and temperature cause the
inner square of the VVM to darken gradually and ADVERSE EVENTS FOLLOWING
irreversibly as shown in Fig. 20. Before opening a vial, IMMUNIZATION
check the status of the VVM. Vaccines used in national immunization programmes are
extremely safe and effective. However, no immune response
is entirely free from the risk of adverse reactions or remote
sequelae.
An AEFI is any untoward medical occurrence which
follows immunization and which does not necessarily have a
causal relationship with the usage of the vaccine. The
adverse event may be any unfavourable or unintended sign,
abnormal laboratory finding, symptom or disease. Reported
adverse events can either be true adverse events, i.e. really a
result of the vaccine or immunization process, or
coincidental events that are not due to the vaccine or
immunization process but are temporally associated with
immunization.
In 2012, the Council for International Organizations of
Medical Sciences (CIOMS} and WHO revised the existing
classification relevant to cause-specific categorization
FIG. 20 of AEFis and a new categorization has been introduced
Different stages of the VVM (Table 35).

TABLE 35
Cause-specific categorization of AEFis (CIOMS/WHO 2012}

Cause-spe~ific type of AEFI Definitio11 ·. .·

Vaccine product-related reaction An AEFI that is caused or precipitated by a vaccine due to one or more of the inherent properties
of the vaccine product.
Vaccine quality defect-related An AEFI that is caused or precipitated by a vaccine that is due to one or more quality defects of
reaction the vaccine product, including its administration device as provided by the manufacturer.
Immunization error-related reaction Immunization error-related reaction: an AEFI that is caused by inappropriate vaccine handling,
(formerly "programme error") prescribing or administration and thus by its nature is preventable.
Immunization anxiety-related An AEFI arising from anxiety about the immunization.
reaction
Coincidental event An AEFI that is caused by something other than the vaccine product, immunization error or
immunization anxiety.

Note : "Immunization" as used in these definitions means the usage of a vaccine for the purpose of immunizing individuals. "Usage" includes
all processes that occur after a vaccine product has left the manufacturing/packaging site, i.e. handling, prescribing and administration of
the vaccine.
Source : (121)
1. Vaccine reactions (121) TABlLE 36
The new cause-specific categorization is important for
decision-making on a vaccine-product, since it dearly Expected
differentiates the two types of possible vaccine reactions. frequency
The first, vaccine product-related reaction, is a reaction in Local reaction Common
an individual's response to the inherent properties of the (pain, swelling, redness)
vaccine, even when the vaccine has been prepared, Oral presentation-none
handled and administered correctly. The second, vaccine Local reaction Upto 50%
quality defect-related reaction, is the defect in a vaccine (pain, swelling, redness)
that occurred during manufacturing process. Such a defect Fever Upto 50%
may have an impact on an individual's response and thus Local reaction Upto 50%
increase the risk of adverse vaccine reactions. In early years (pain, swelling, redness)
of immunization programmes, a few major incidences of Hepatitis B Local reaction Adults up to
vaccine quality defect-related reactions were reported (e.g. (pain, swelling, redness) 30%, Children
upto 5%
Cutter case study). However, due to introduction of Fever 1-6%
improved Good Manufacturing Practices · (GMP), such
Hib Local reaction 5-15%
defects are now very rare. (pain, swelling, redness)
Fever 2-10%
Vaccine reactions may be classified into common, minor
reactions or rare, more serious reactions. Most vaccine Japanese Local reaction, Upto 20%
encephalitis low-grade fever, myalgia,
reactions are minor and settle on their own. More serious gastrointestinal upset
reactions are very rare and, in general, do not result in
Measles/ Local reaction Upto 103
long-term problems. IMMR (pain, swelling, redness)
Irritability, malaise and Upto5%
COMMON, MINOR VACCINE REACTIONS II Pneumococcal non-specific symptoms, fever
Local reaction 30-503
The purpose of a vaccine is to induce immunity by (pain, swelling, redness)
causing the recipient's immune system to react to the Poliomyelitis None
vaccine. Local reaction, fever and systemic symptoms can (OPV)
result as part of the immune response. In addition, some of I
Poliomyelitis None
the vaccine's components (e.g. aluminium adjuvant,
stabilizers or preservatives) can lead to reactions. A I (IPV)
Rabies Local and/or general reaction 15-25%
successful vaccine reduces these reactions to a minimum depending on type of vaccine
while producing the best possible immunity. (see product information)
Meningococcal Mild local reactions Upto 71%
The local reactions include pain, swelling and/or redness disease
at the injection site and can be expected in about 103 of I
vaccinees, except for those injected with DTP (whole cell), ITetanus/Td Local reaction
(pain, swelling, redness)b
Upto 10%
or tetanus boosters, where up to half can be affected. BCG Malaise and non-specific Upto253
causes a specific local reaction that starts as a papule symptoms
l
{lump) two or more weeks after immunization, that then Tick-borne Local reaction Upto 10%
becomes ulcerated and heals after several months, encephalitis (pain, swelling, redness)
leaving a scar. Keloid (thickened scar tissue) from the BCG
lesion is more common among asian and african
II Typhoid fever Depends on type of vaccine
use (see product information)
I
populations. ' Yellow fever Headache 10%
Influenza-like symptoms 22%
The systemic reactions include fever and occur in about Local reaction 53
103 or less of vaccinees, except for DTP where it is again (pain, swelling, redness)
about half. Other common systemic reactions (e.g., With whole-cell pertussis vaccine. Rates for acellular pertussis
irritability, malaise, 'off-colour', loss of appetite) can also vaccine are lower.
b
occur after DTP. For measles/MMR and OPV the sytemic Rate of local reactions likely to increase with booster doses,
up to 50-85%.
reactions arise from vaccine virus infection. Measles vaccine
causes fever, rash and/or conjunctivitis, and affects 5-153 Source : (132)
of vaccinees. It is very mild compared to 'wild' measles, but
for severely immunocompromised individuals, it can be RARE, MORE SERIOUS VACCINE REACTIONS (121)
severe, even fatal. Vaccine reactions for mumps (swollen 'Serious' and 'severe' are often used as interchangeable
parotid gland) and rubella (joint pains and swollen lymph terms but they are not. An AEFI will be considered serious, if
nodes) affect less than 1 3 of children. Rubella vaccine it results in death, is life-threatening, requires in-patient
causes symptoms more often in adults, with 15% suffering hospitalization or prolongation of existing hospitalization,
from joint pains. Systemic reactions from OPV affect less results in persistent or significant disability/incapacity, is a
than 1 % of vaccinees with diarrhoea, headache and/or congenital anomaly/birth defect, or required intervention to
muscle pain. prevent permanent impairment or damage. Severe is used to
describe the intensity of a specification event (as in mild,
The common minor vaccine reactions and their expected moderate or severe). The event itself, however, may be of
frequency are as shown in Table 36. relatively minor medical significance. (For example, fever is
 I:P;DEMJDLOC,Y !-\NU CPIDEMlCi_GC1C

a common relatively minor medical event, but according to thrombocytopenia, HHEs, persistent inconsolable
its severity it can be graded as mild fever or moderate fever. screaming) do not lead to long-term problems. Anaphylaxis,
Anaphylaxis is always a serious event and life-threatening.) while potentially fatal, is treatable without leaving any long-
Table 37 details the rare vaccine reactions; the onset term effects. Although encephalopthy is included as a rare
interval, the rate per doses and the case definitions. Most of reaction to measles or DTP vaccine, it is not certain that
the rare and more serious vaccine reactions (e.g. seizures, these vaccines in fact cause encephalopathy.

Vaccine Reaction Onset interval Rate/doses

BCG Suppurative lymphadenitis 2-6 months 1-10/104
BCG osteitis 1-12 months 1-700/106
Disseminated BCG infection 1-12 months 0.19-1.56/106
Hib None
Hepatitis B Anaphylaxis 0-1 hour 1.1/106
Influenza Anaphylaxis 0.7/10 6
(inactivated) Guillain-Barre syndrome (GBS) 1-2/106
Oculo-respiratory syndrome 76/10 6
Influenza (live- Anaphylaxis 2/106
attenuated) Wheezing (children 6-11 months age) 14/100
Japanese Neurologic events (encephalitis, 1-2.3/106
encephalitis encephalopathy $,
(inactivated) peripheral neuropathy)
Measles/MMR/ Febrile seizures 6-12 days 3/103
MR. Thrombocytopaenia 15-35 days 3/104
Anaphylaxis 0-1 hour -1/106
Encephalopathy s 6-12 days <1/10 6
Oral poliomyelitis VAPP 4-30 days 2-4/lQ6t
Pertussis (DTwP) Persistent ( >3 hours) inconsolable screaming 0-24 hours <1/100
Seizures tt 0-3 days <1/100
Hypotonic, hypo responsive episode (HHE) 0-48 hours 1-2/103
Anaphylaxis 0-1 hour 20/10 6
Encephalopathy $ 0-2 days 0-1/10 6
Pneumococcal None proven ±
Rotavirus None known••
Tetanus toxoid, DT Brachia! neuritis 2-28 days 5-10/106
Anaphylaxis 0-1 hour 1-6/106
Yellow fever Vaccine-associated viscerotropic disease ••• 1/106
Varicella Febrile seizures 4-9/l04tt

Notes:
Reactions (except anaphylaxis) do not occur if already immune (-90% of those receiving a second dose are immune): children over six
years unlikely to have febrile seizures.
VAPP Risk is higher following the first dose (1 in 750,000 compared to 1 in 5.1 million for subsequent doses), and for adults and
immunocompromised.
± No proven risk of severe febrile or anaphylactic reactions or neurological disorders (e.g. Guillain-Barre syndrome)
•• Post-marketing surveillance of currently available rotavirus vaccines has detected a small increased risk of intussusception
100,000 infants vaccinated) in some settings shortly after the first dose of rotavirus vaccine.
Very rare in children
tt Seizures are mostly febrile and the risk depends on age, with much lower risk in infants under the age of four months.
Although encephalopathy is included as a rare possible reaction to measles, JE or DTP vaccines, it is not certain that these
cause encephalopathy. Hence, further scientific evaluation is necessary.
other serious events have been reported following immunization, it is likely that these events are coincidental, not true rei:tct1•ons
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _A_D_V_E_R_S_E_-_EV_EN_T_s_-_F_O_L_LO_Vl_IIN_G_l_M_M_U_N_ll_ZA_T_l_O_N_ _ .• 113 ·
The case definitions and treatments of adverse events following immunization are as follows (121) :

Adverse event Case definition Treatment Vaccines

Acute flaccid Acute onset of flaccid paralysis within 4 to 30 days of receipt No specific treatment OPV
paralysis (vaccine of oral poliovirus (OPV), or within 4 to 75 days after contact available; supportive
associated paralytic with a vaccine recipient with isolation of vaccine virus and care.
poliomyelitis) absence of wild polio virus in the stool, and neurological
deficits remaining 60 days after onset, or death.

Anaphylactoid Exaggerated acute allergic reaction, occurring within 2 hours Self-limiting; All
reaction (acute after immunization, characterized by one or more of the anti-histamines
hypersensitivity following: may be helpful.
reaction) • wheezing and shortness of breath due to bronchospasm
• laryngospasm/laryngeal oedema
• one or more skin manifestations, e.g. hives, facial oedema,
or generalized oedema.
Less severe allergic reactions do not need to be reported.

Anaphylaxis Severe immediate (within 1 hour) allergic reaction leading to Adrenaline injection All
circulatory failure with or without bronchospasm and/or
laryngospasm/laryngeal oedema

Arthralgia Joint pain usually including the small peripheral joints. Self-limiting; Rubella,
Persistent, if lasting longer than 10 days, transient; if lasting analgesics MMR
up to 10 days.

Brachia! neuritis Dysfunction of nerves supplying the arm/shoulder without Symptomatic only; Tetanus
other involvement of nervous system. A deep steady, often analgesics.
severe aching pain in the shoulder and upper arm followed
in days or weeks by weakness and wasting in arm/shoulder
muscles. Sensory loss may be present, but is less prominent.
May present on the same or the opposite side to the injection
and sometimes affects both arms.

Disseminated BCG Widespread infection occurring within 1 to 12 months after Should be treated BCG
infections BCG vaccination and confirmed by isolation of with anti-tuberculous
Mycobacterium bovis BCG strain. Usually in regimens including
immunocompromised individuals. isoniazid and rifampicin

Encephalopathy Acute onset of major illness characterized by any two of the No specific treatment Measles,
following three conditions: available; supportive Pertussis
• seizures care.
• severe alteration in level of consciousness lasting for
one day or more
• distinct change in behaviour lasting one day or more.
Needs to occur within 48 hours of DTP vaccine or from
7 to 12 days after measles or MMR vaccine, to be related
to immunization.

Fever The fever can be classified (based on rectal temperature) Symptomatic; All
as mild (38 to 38.9°C), high (39 to 40.4°C) and paracetamol.
extreme (40.5°C or higher). Fever on its own does not
need to be reported.

Hypotonic, Event of sudden onset occurring within 48 (usually less The episode is Mainly
hyporesponsive than 12) hours of vaccination and lasting from one minute transient and DTP,
episode (HHE or to several hours, in children younger than 10 years of age. self-limiting, and does rarely
shock-collapse) All of the following must be present : not require specific others
• limpness (hypotonic) treatment. It is not
• reduced responsiveness (hyporesponsive) a contraindication to
• pallor or cyanosis - or failure to observed/recall. further doses of the
vaccine.
 PRINCIPLES OF EPIDEMIOLOGY AND EPIDEMIOLOGIC METHODS

Adverse event Case definition Treatment Vaccines

Injection site Fluctuant or draining fluid-filled lesion at the site of injection. Incise and drain; All
abscess Bacterial if evidence of infection (e.g. purulent, inflammatory antibiotics if
signs, fever, culture), sterile abscess if not. bacterial.

Lymphadenitis Either at least one lymph nodes enlarged to > 1.5 cm in size Heals spontaneously BCG
(includes (one adult finger width), or a draining sinus over a lymph (over months) and
suppurative node. Almost exclusively caused by BCG and then occurring best not to treat
lymphadenitis) within 2 to 6 months after receipt of BCG vaccine, on the unless lesion is
same side as inoculation (mostly axilliary). sticking to skin. If
so,or already draining,
surgical drainage and
local instillation of
anti-tuberculous drug.
Systemic treatment
with anti-tuberculous
drugs is ineffective.

Osteitis/ Inflammation of the bone with isolation of Mycobacterium Should be treated with BCG
Osteomyelitis bovis BCG strain. anti-tuberculous
regimens including
isoniazid and rifampicin

Persistent Inconsolable continuous crying lasting 3 hours or longer Settles within a day or DTP,
inconsolable accompanied by high-pitched screaming. so; analgesics may . Pertussis
screaming help

Seizures Occurrence of generalized convulsions that are not Self-limiting supportive All,
accompanied by focal neurological signs or symptoms. care; paracetamol and especially
Febrile seizures: if temperature elevated >38°C (rectal) cooling if febrile; rarely Pertussis,
Afebrile seizures : if temperature normal. anticonvulsants. Measles

Sepsis Acute onset of severe generalized illness due to bacterial Critical to recognize All
infection and confirmed (if possible) by positive blood and treat early. Urgent
culture. Needs to be reported as possible indicator of transfer to hospital for
programme error. parenteral antibiotics
and fluids

Severe local Redness and/or swelling centred at the site of injection Settles spontaneously All
reaction and one or more of the following: within a few days to
• swelling beyond the nearest joint a week. Symptomatic
• pain, redness, and swelling of more than 3 days duration treatment with
• requires hospitalization. analgesics. Antibiotics
Local reactions of lesser intensity occur commonly and are are inappropriate.
trivial and do not need to be reported.

Thrombocytopaenia Serum platelet count of less than 50,000/ml leading to Usually mild and MMR
bruising and/or bleeding. self-limiting;
occasionally may need
steroid or platelets.

Toxic shock Abrupt onset of fever, vomiting and watery diarrhoea within a Critical to recognize All
syndrome (TSS) few hours of immunization. Often leading to death within and treat early. Urgent
24 to 48 hours. Needs to be reported as possible indicator of transfer to hospital
programme error. for parenteral
antibiotics and fluids.

RECOGNITION OF ANAPHYLAXIS (121) antibiotic which it contains.

Administration of antisera may occasionally give rise to Anaphylaxis is a severe reaction of rapid onset,
anaphylactic shock and serum sickness. Many viral vaccines characterized by circulatory collapse. The early signs of
contain traces of various antibiotics used in their anaphylaxis are generalized erythema and .urticaria with
preparation and some individuals may be sensitive to the upper and/or lower respiratory tract obstruction. In more
severe cases, limpness, pallor, loss of consciousness and • Generalized itching of skin especially
hypotension may also become evident. Vaccinators should hands, forehead and eyes in children
be able to recognize the following signs and symptoms of Note ·Skin changes alone without life
anaphylaxis: threatening cardio-respiratory signs do
not signify an anaphylactic reaction
Gastrointestinal • Diarrhoea
Respiratory Airway • Colicky abdominal pain
• Throat and tongue swelling (pharyngeal/ • Vomiting
laryngeal oedema) the patient has • Incontinence
difficulty in breathing and swallowing and In general, the more severe the reaction, the more rapid the
feels that the throat is closing up.
onset. Most life-threatening reactions begin within 10 minutes
• Hoarse voice. of immunization. It is advisable to keep the recipient under
• Stridor observation for at least 20 minutes after the injection.
Breathing Symptoms limited to only one system can occur, leading to
• Bronchospasm delay in diagnosis. Biphasic reactions where symptoms recur
• Respiratory distress 2 or more of the 8 to 12 hours after onset of the original attack and prolonged
following: attacks lasting up to 48 hours have been described.
Tachypnoea
Time Scale Signs and symptoms Severity
- Increased use of accessory respiratory of anaphylaxis
muscles
- Recession Early warning Dizziness, perinea! burning, Mild
signs warmth, pruritus
- Cyanosis
• Grunting Flushing, urticaria, nasal congestion, Mild to
sneezing, lacrimation, angioedema moderate
• Respiratory arrest

il
Hoarseness, nausea, vomiting, Moderate
Cardiovascular • Hypotension
sub-sternal pressure
• Clinical diagnosis of uncompensated
shock, indicated by the combination of Laryngeal oedema, dyspnoea, Moderate
at least three of the following: abdominal pain to severe
Tachycardia Late, life-threat- Bronchospasm, stridor, collapse, Severe
Capillary refill time >3 seconds ening symptoms hypotension, dysrhythmias
Reduced central pulse volume
- Decreased level of consciousness or 2. lmmtmizi!.Hon ern3:r-reTiated rnacforH1§ (121)
loss of consciousness "Immunization" means the usage of a vaccine for the
• Cardiac arrest purpose of immunizing individuals. "Usage" includes all
• Bradycardia (a slow pulse) is usually a processes that occur after a vaccine product has left the
late feature, often preceding cardiac manufacturing/packaging site, i.e. handling, prescribing and
arrest administration of the vaccine.
CNS • Confusion/ Agitation An immunization error-related reaction may lead to a
• Headache cluster of events associated with immunization. These
• Loss of consciousness clusters are usually associated with a particular provider, or
Dermatologic or • Tingling of lips health facility, or even a single vial of vaccine that has been
mucosa/ • Generalized urticaria or generalized inappropriately prepared or contaminated. Immunization
erythema
errors-related reactions can also affect many vials. For
• Angioedema, localized or generalized example, freezing vaccine during transport may lead to an
(angioedema is similar to urticaria but
involves swelling of deeper tissues, most increase in local reactions.
commonly in the eyelids and lips, and Table 38 shows the immunization error-related reactions
sometimes in the mouth and throat) (121).

TABLE 38
Immunization error rel,11ed 1'l'i1clinn~

Immunization error Related reaction

Error in vaccine Exposure to excess heat or cold as a result of Systemic or local reactions due to changes in the physical
handling inappropriate transport, storage or handling of nature of the vaccine such as agglutination of aluminium-
the vaccine (and its diluent) where applicable. based excipients in freeze-sensitive vaccines.
Use of a product after the expiry date. Failure to vaccinate as a result of loss of potency or non-
viability of an attenuated product.
Error in vaccine prescribing Failure to adhere to a contraindication. Anaphylaxis, disseminated infection with an attenuated
or non-adherence to live, VAPP.
recommendations for use Failure to adhere to vaccine indications or Systemic and/or local reactions, neurologic, muscular,
prescription (dose or schedule). vascular or bony injury due to incorrect injection site,
equipment or technique.
Error in administration Use of an incorrect diluent or injection of a Failure to vaccinate due to incorrect diluent, Reaction due
product other than the intended vaccine. to the inherent properties of whatever was administered
other than the intended vaccine or diluent.
Incorrect sterile technique or inappropriate Infection at the site of injection/beyond the site of
procedure with a multidose vial. injection.
 PRINCIPLES OF EPIDEMIOLOGY AND EPIDEMIOLOGIC METHODS

In the past, the most common immunization error was an 4. Coincidental event§
infection (including bloodborne virus) as a result of non- Occasionally following immunization there may occur a
sterile-injection. The infection could manifest as a local disease totally unconnected with the immunizing agent.
reaction (e.g. suppuration, abscess), systemic effect (e.g. Vaccines are normally scheduled early in life, when
sepsis or toxic shock syndrome), or blood-borne virus infections and other illnesses are common, including
infection (e.g. HIV, hepatitis B or hepatitis C). However, with manifestations of an underlying congenital or neurological
the introduction of auto disabled (AD) syringes, infection condition. The mechanism seems to be that the individual is
occurrence has reduced significantly. Still, infection can harbouring the infectious agent and the administration of
occur in cases of mass vaccination or disaster stituations, the vaccine shortens the incubation period and produces the
particularly if there is any shortage or problems with logistics disease or what may have been otherwise only a latent
and supplies. This can be avoided by proper planning and infection is converted into a clinical attack.
preparedness of programme managers.
The symptoms arising from an immunization error may PRECAUTIONS TO BE TAKEN
help to identify the likely cause. For example, children Before administration of the antiserum or antitoxin, it is
immunized with contaminated vaccine (usually the necessary to test for sensitivity reaction. This can be done in
bacterium Staphylococcus aureus) become sick within a few 2 ways: (a) instilling a drop of the preparation into the
hours; local tenderness and tissue infiltration, vomiting, conjunctiva! sac. A sensitized person will develop pricking of
diarrhoea, cyanosis and a high temperature are the most the conjunctiva. (b) a more reliable way of testing is by
frequent symptoms. Bacteriological examination of the vial, intradermal injection of 0.2 ml of antiserum diluted 1 : 10
if still available, can confirm the source of the infection. with saline. A sensitized patient will develop a wheal and
flare within 10 minutes at the site of injection. It should be
3. Immunization anxiety-related reactions (121) borne in mind that these tests are not infallible.
Individuals and groups can react in anticipation to and as Adrenaline (1:1000 solution) should be kept ready when
a result of an injection of any kind. This reaction is unrelated giving foreign serum. In the event of anaphylaxis, for an
to content of the vaccine. Fainting is relatively common. adult, 0.5 ml of adrenaline solution should be injected
During fainting, the individual suddenly becomes pale, loses intramuscularly immediately, followed by 0.5 ml every
consciousness and collapses to the ground. Fainting is 20 minutes if the systolic blood pressure is below 100 mm of
sometimes accompanied by brief clonic seizure activity (i.e. mercury. An injection of antihistaminic drug should also be
rhythmic jerking of the limbs), but this requires no specific given, e.g., 10-20 mg of chlorpheniramine maleate by the
treatment or investigation. Fainting is relatively common intramuscular route, to minimize the after-effects such as
after immunization of adults and adolescents, but very rare urticaria or oedema. The patient should be observed for
in young children. It is managed by simply placing the 30 minutes after any serum injection.
patient in a recumbent position. Recovery of consciousness The risk of adverse reactions can be reduced by proper
occurs within a minute or two, but patients may take some sterilization of syringes and needles, by proper selection of
more time to recover fully. Table 39 shows the difference the subject and the product, and if due care is exercised in
between fainting attack and anaphylaxis. carrying out the procedure. Measles and BCG vaccines
should be reconstituted only with the diluent supplied by the
An anxiety spell can lead to pale, fearful appearance and manufacturer. Reconstituted vaccine should be discarded at
symptoms of hyperventilation (light-headedness, dizziness, the end of each immunization session and NEVER retained
tingling in the hands and around the mouth). Breath-holding for use in subsequent sessions. In the refrigerator of the
occurs in young children and will lead to facial flushing and immunization centre, no other drug and substances should
cyanosis. It can end in unconsciousness, during which be stored beside vaccines. Training of immunization worker
breathing resumes. Anaphylaxis develops over several and their close supervision to ensure that proper procedures
minutes upto a few hours and usually involves multiple body are being followed are essential to prevent complications
systems. Unconsciousness is rarely the sole manifestation of and deaths following immunization. Careful epidemiological
anaphylaxis - it only occurs as a late event in severe cases. investigation should be carried out when an adverse event
A strong central pulse (e.g. carotid) is maintained during a following immunization occurs to pinpoint the cause of the
faint, but not in anaphylaxis. incident and to correct immunization practices (133, 121).

TABLE 39
Difference between a fainting attack and anaphylaxis

Clinical features Fainting

Timing Before, during or few minutes after injection
Skin Generalized pallor, cold clammy skin
lips,
Respiratory system Normal breathing Tachypnoea, difficulty in breathing, wheezing, stridor,
Shallow breathing hoarseness, cyanosis, recession of intercostal spaces
Cardiovascular Bradycardia, weak pulse, carotid pulse felt, hypotension Tachycardia, weak pulse, carotid pulse may be weak,
may occur-reversed by supine position hypotension not reversed by supine position
GIT Vomiting Vomiting, diarrhoea, abdominal cramps
CNS Faintishness, light-headedness relieved by supine posture Anxiety and distress, loss of consciousness not
relieved by supine posture
Panic attack- no hypotension, pallor, wheeze, or urticaria! rash or swelling. May have flushing or blotchy skin.
 adverse events • Brachia] neuritis (2-28 days after
foHowing immunization (121) tetanus containing vaccine)
• Thrombocytopaenia (15-35 days
The suggested reportable events believed by the public or
after measles/MMR)
health workers to be caused by immunization are listed
• lntussusception commonly after
below and could be considered for inclusion in the AEFI
rotavirus
surveillance system. There is no point in reporting common
minor reactions such as local reactions, fever and self-
limiting systemic symptoms. Occurring between • Lymphadenitis
1 and 12 months • Disseminated BCG infection
after BCG • Osteitis/Osteomyelitis
immunization

Occurring within • Anaphylactoid reaction {acute No time limit Any death, hospitalization, disability
24-48 hours of hypersensitivity reaction) or other severe and unusual events that
immunization • Anaphylaxis are thought by health workers or the
• Persistent {more than 3 hours) public to be related to immunization
inconsolable screaming
• Hypotonic hyporesponsive episode Once the report has been received, an assessment should be
(HHE) made to determine whether or not an investigation is needed.
• Toxic shock syndrome (TSS) The urgency of the investigation depends on the situation.

Investigating AEFI clusters

Occurring within • Severe local reaction
7 days of • Sepsis A cluster of AEFI is defined as two or more cases of the
immunization • Injection site abscess (bacterial/sterile) same adverse event related in time, place or vaccine
administration. Cluster investigation begins by establishing
the case definition and identifying all cases that meet the
Occurring within • Seizures, including febrile seizures case definition.
14 days of (6-12 days for measles/MMR;
A cluster of similar adverse events is likely to arise from
immunization 0-2 days for DTP) programme errors. If the event also occured in unimmunized
• Encephalopathy (6-12 days for people, it may be coincidental. If all cases received the same
measles/MMR; 0-2 days for DTP) vaccine or lot, and there are no similar cases in the
community, a problem with the vaccine is likely. If the event
Occurring within • Acute flaccid paralysis (4-30 days for is a known vaccine reaction but occurring at an increased
3 months of OPV recipient; 4-75 days for rate, a programme error or a vaccine problem are likely
immunization contact) causes (Fig. 21).

\ Cl~~ter of AEF!s I
+
/\
/ \
I \

/ \ /;'
/ All cases \ All cases \ Similar
// Programme
/from only one \ No / got same \ No / Known No illness in error,
'. facility (same )---4>< \.____.( vaccine others who
vaccine coincidental or
\ lot used / I \ reaction ? didn't get
or lot? 'unknown'
\at others)?/ // \\\. vaccine?
\ . ,//
\ // '

\\ / I
\I \ I

Yes~ Yes"t Yes

/\
Programme error / \ /\
\ Coincidental event
I \ .·./ \
I \
\
/ \ r··
// \

Immunization error, / Similar \

(transport/storage No/ illness in \ / Rate of \ Immunization error ·-1
· · ·No
/1 reaction
·
w1thm \_4 or vaccine quality
error) or vaccine ff--\ ot~er; who ·
quality defect reaction \ didn_t get / \ the expected / j defect reaction j
\ rate? /
\~accme/
\\ I
/
\\ I \ //
\ /
Yes'{ YesY.....
ICoincid~n--ta_l_e_v_e-nt- Vaccine product
related reaction
Source : (121) FIG. 21
Identifying cause of AEFI cluster
 PRINCIPLES OF EPIDEMIOLOGY AND EPIDEMIOLOGIC METHODS

hrnesHgation. of an AEfl (121) 4. Formulate a • On the likely/possible cause(s) of the

AN AEFI investigation follows standard epidemiological working event.
investigation principles. In addition, investigation of the hypothesis:
vaccine(s), immunization techniques and procedures, and 5. Test working • Does case distribution match working
service in action needs to be conducted. hypothesis hypothesis ?
STEPS IN AN AEFI INVESTIGATION • Occasionally, laboratory tests may help.
Step Actions 6. Conclude • Reach a conclusion on the cause.
investigation• Complete AEFI Investigation Form.
1. Confirm • Obtain patient's medical file
• Take corrective action, and recommend
information (or other clinical record}.
further action
in report • Check details about patient and event
from medical file and document
A series of cases without comparison of disease and
information.
exposure among controls is not likely to reveal the cause of
• Identify any other cases that need to be
the AEFI, except in the case of programme errors. Clear case
included in the investigation.
definitions, from the guidelines on reporting or defined
2. Investigate • Immunization history. during the investigation, are essential. The investigation
and collect • Previous medical history, including prior needs to identify all cases in the community and find out the
data: history of similar reaction or other outcomes for all those who received the suspect vaccine.
About the allergies. A working hypothesis should be established as soon as there
patient: • Family history of similar events. is sufficient information. Laboratory testing may sometimes
confirm or rule out the suspected cause. The vaccine may be
About the • History, clinical description, any relevant tested for sterility and adjuvant (e.g. aluminium content);
event: laboratory results about the AEFI and the diluent for sterility and chemical composition; and the
diagnosis of the event. needles and syringe for sterility. Testing should be requested
' Treatment, whether hospitalized, and on a clear suspicion and not as a routine, and never before
outcome. the working hypothesis has been formulated.
About the • Conditions under which the vaccine was Contraindications to vaccination
suspected shipped, its present storage condition,
vaccine(s}: state of vaccine vial monitor, and Vaccines are very rarely contraindicated. However, it is
temperature record of refrigerator. important to check for contraindications to avoid serious
• Storage of vaccine before it arrived at reactions. For example, vaccines are contraindicated if there
health facility, where it has come from is serious allergy to the vaccine or its components. Live
higher up the cold chain, vaccine vaccines should not be given to immune-deficient children.
monitor card. The main contraindication to the administration of
vaccines are summarized in Table 40.
About • Whether others received the same
other vaccine and developed illness. DISEASE PREVENTION AND CONTROL
people: • Whether others had similar illness (may
Every disease has certain weak points susceptible to
need case definition); if so exposure of
attack. The basic approach in controlling disease is to
cases of suspect vaccine(s).
identify these weak points and break the weakest links in the
• Investigate the local immunization
chain of transmission (Fig. 16). This requires sound
service.
epidemiological knowledge of the disease - that is its
3. Assess the • Vaccine storage (including open vials), magnitude, distribution in time, place and person,
service by: distribution, and disposal. multifactorial causation, sources of infection and dynamics
asking • Diluent storage and distribution. of transmission.
about: • Reconstitution (process and time kept). Frequently it may be necessary to institute more than one
• Use and sterilization of syringes and method of control simultaneously. The choice of methods
needles. will depend upon factors such as availability of proper tools
• Details of training in immunization and techniques, relative cost effectiveness, efficiency and
practice, supervision and vaccinator(s). acceptability. Although effective control of a disease requires
• Number of immunizations greater than knowledge of its multifactorial causation, removal or
normal? elimination of a single known essential link or the weakest
link may be sufficient to control a disease, even if complete
Observing • Refrigerator - what else is stored (note if
knowledge about the aetiology of the disease in question is
the service similar containers stored next to vaccine
lacking. The classic example is that of John Snow controlling
in action: vials which could be confused); which
the cholera epidemic in London, by removing the handle of
vaccines/diluents stored with other
the incriminated water pump.
drugs; whether any vials have lost their
label. Disease control involves all the measures designed to
• Immunization procedures (reconstitution, prevent or reduce as much as possible the incidence,
drawing up vaccine, injection prevalence and consequences of disease (134). This
technique, safety of needles and includes community participation, political support and
syringes; disposal of opened vials). intersectoral coordination (135). Control measures should
• Do any open vials look contaminated ? not be delayed because of incomplete or lack of accurate
knowledge of the aetiological agent.