Notes

Classification of vaccines

01. Live attenuated vaccines
Live attenuated vaccines may cause severe or fatal reactions as a result of uncon￾trolled replication (growth) of the vaccine virus. This only occurs in persons with
immunodeficiency (e.g. from leukemia, treatment with certain drugs, or HIV in￾fection).
Live attenuated vaccines are labile, and can be damaged or destroyed by heat and
light. They must be handled and stored carefully.
Currently available live attenuated viral vaccines include measles, mumps, rubella,
varicella, yellow fever, oral polio and influenza (intranasal). Live attenuated bacte￾rial vaccines include BCG and oral typhoid vaccine.

02. Inactivated vaccines
Whole cell, toxoid, subunit, recombinant and conjugate vaccines all come under
the category of inactivated vaccines, in that they are non-infectious but retain the
ability to stimulate the immune system.
Live parenteral (injected) vaccines (measles, rubella, MMR, varicella, and yellow
fever) that are not administered simultaneously should be separated by at least 4
weeks. This precaution is intended to reduce or eliminate interference from the
vaccine given first on the vaccine given later.
Live vaccines administered by a nonparenteral route (OPV, oral typhoid, live at￾tenuated influenza) are not believed to interfere with each other if not given si￾multaneously. These vaccines may be given at any time before or after each other.
All other combinations of two inactivated vaccines or live and inactivated vac￾cines may be given at any time before or after each other.
Vaccine recipient:
♦ is unwell today,
♦ has had a reaction to previous vaccinations or any other drugs,
♦ has had any allergies to vaccines or vaccine components (e.g. neomy￾cin),
♦ is having treatment which lowers immunity (e.g. steroids such as corti￾sone and prednisolone, radiotherapy, or chemotherapy),
♦ has a disease which lowers immunity (e.g. leukaemia, cancer,HIV),♦ has had a vaccine containing live viruses within the last month (e.g. mea￾sles, poliomyelitis, yellow fever or rubella vaccines), or an injection of
immunoglobulin or a blood transfusion within the last three months,
♦ has a chronic illness,
♦ has a disease of the brain or the spinal cord.
False contraindications to vaccination
Conditions listed below are not contraindications to vaccination. Children with
these conditions should be vaccinated with all recommended vaccines:
♦ mild illness without fever (T <38.5°C),
♦ family history of any adverse events following immunization,
♦ past history of convulsions,
♦ treatment with antibiotics,
♦ treatment with locally acting (inhaled or low-dose topical) steroids,
♦ asthma, eczema, atopy,
♦ previous pertussis-like illness, measles, rubella, mumps or meningococcal
disease,
♦ prematurity (vaccination should not be postponed),
♦ history of neonatal jaundice,
♦ low weight in an otherwise healthy child,
♦ any stable neurological conditions including cerebral palsy and Down
syndrome,
♦ contact with an infectious disease,
♦ child’s mother is pregnant,
♦ child to be vaccinated is being breastfed,
♦ poorly documented vaccination history
Storage
Vaccines that are not stored and transported correctly will lose potency. Vaccines
must be handled and stored as recommended in the manufacturers’ package in￾serts. The temperatures at which vaccines are transported and stored should be
monitored according to national guidelines. Vaccines must not be administered
after their expiry date, and vaccines that have undergone a breach in the cold
chain should not be used without appropriate consultation.
The general rule for most vaccines is that they should be refrigerated at +2oC to
+8oC and NOT FROZEN. Vaccines such as DTP, DT, aTd, TT Hib, hepatitis B
and Hib containing liquid Pentavalent vaccines are inactivated by freezing. De￾tailed guidelines on correct storage and transport are given under Chapter VI; i.e.
Maintenance of cold chain of EPI vaccines.
Open vial policy
After considering all the relevant factors the National Advisory Committee on
Communicable Diseases decided to introduce the open vial policy in Sri Lanka
from year 2005. Therefore open multi dose vials of all liquid vaccines (OPV,
DPT, TT, DT, aTd, Hep B, and DTP-Hib-Hep B) could be reused in subsequent
sessions.
After using one or more doses of vaccines from these multi dose vaccine vials
during an immunization session, remaining doses could be reused in subsequent
immunization sessions within 4 weeks of their opening. However all the following
conditions must be fulfilled before reusing the vaccines so that the potency of
vaccines and the safety of their administration could be guaranteed.
The expiry date has not been reached
♦ The vaccines should be stored and transported under appropriate cold chain
conditions. All conditions which apply for the maintenance of cold chain for
the unopened vials should apply for the opened vials as well.
♦ The opened vials that are returned to the MOH office should be kept in a
separate container when they are stored in the refrigerator (+2oC to +8oC )
after the clinic session.
♦ In every clinic session previously opened vaccine vials should be used first,
before opening any new vaccine vials.
Approximate number of doses in the opened vials should also be included in the vac￾cine movement register before sending vaccines to the clinics and after receiving from the clinic
Adverse Events Following Immunization (AEFI)
Recipients of vaccine should remain under observation until they are seen to be in
good health and not be experiencing an immediate adverse reaction. It is not pos￾sible to specify an exact length of time for post-vaccination observations but it is
recommended that recipients should remain in the clinic/hospital for about 15
minutes. Parents or guardian should be provided with the necessary information
before leaving the clinic on how to act if the child develops an adverse event following immunization
Children who have had serious adverse events following vaccination may be sub￾sequently vaccinated (in the event of absence of absolute contraindications) under
close medical supervision at a MOH Office or in a hospital.
Anaphylaxis
The most serious immediate reaction to vaccination, though it is rare, is anaphy￾laxis. The incidence of anaphylaxis reactions vary with the type of vaccine. But
the incidence of true anaphylaxis is only 1-3 cases per million vaccinations. Any
member of the health staff carrying out vaccination must be able to distinguish
between anaphylaxis, convulsions, fainting and attend to the initial management.
[Refer to Chapter on Anaphylaxis]
Reporting of Adverse Events Following Immunization (AEFI)
Adverse events following immunization should be reported to the respective
MOH. In the case of very severe adverse events the Epidemiology Unit should
be informed promptly (telephone 0112681548 or fax 0112696583). The MOOH
should investigate all the severe AEFIs. The Monthly Surveillance Report on
AEFIs which is send to the Epidemiology Unit should include all the AEFIs
reported to the MOH during the given month.
Administration of two or more vaccines on the same day
Different antigens/vaccines could be given on the same day, if necessary. Inacti￾vated vaccines and live attenuated virus vaccines, particularly those in the national
EPI schedule (childhood schedule) can generally be given during the same visit.
Vaccines that should be administered by injections should be given at different
sites (e.g. DPT, MR, MMR and hepatitis B). More than one live attenuated virus
vaccine may be given on the same day; but if only one is given, a second live at￾tenuated vaccine should not be given within 4 weeks of the first vaccine because
the response to the second vaccine may be diminished. In addition there is a spe￾cific interaction between some vaccines (e.g. yellow fever and cholera vaccines)
and they should not be given within 4 weeks of each other.
Different vaccines should not be mixed in the same syringe unless it is clearly
stated in the instructions of the manufacturer (given in the information schedule
supplied by the vaccine supplier). Different vaccines given to a person on the
same day should be injected at different sites using different syringes.
The milestones of immunization in Sri Lanka
1886 Vaccination against smallpox introduced under the Vaccination Ordinance
1949 BCG Vaccination introduced against tuberculosis
1961 “Triple” vaccination introduced against diphtheria whooping cough and
Tetanus
1962 Oral polio vaccine introduced
1963 BCG vaccination of newborn introduced
1969 Tetanus Toxoid administration to pregnant mothers introduced
1978 Launching of the Expanded Programme on Immunization
1981 Revision of the immunization schedule and the introduction of a modified
list of contraindications
1984 Introduction of Measles vaccine to the EPI
1985 Strengthening of cold chain and logistics in EPI
1988 Introduction of Killed JE vaccine to the EPI
1989 Universal Childhood Immunization (UCI) achieved with over 80% coverage
among infant immunizations
1991 Revision of Tetanus Toxoid schedule
1995 Conduct of first Polio National Immunization Days1996 Introduction of
Rubella vaccine
1996 Conduct of the second Polio National Immunization Days
1997 Conduct of the third Polio National Immunization Days
1998 Conduct of the fourth Polio National Immunization Days
1999 Conduct of the Polio National Immunization Days
2000 Consultative meeting held to review the National Immunization Schedule
2001 Introduction of the new National Immunization Schedule;
♦ DTP at 2, 4 and 6 months of age
♦ Introduced MR vaccine at 3 years
♦ Introduced aTd at 10 years
2003 Introduction of HBV vaccine and AD syringes to the EPI
2003 Measles catch-up immunization programme
2005 MR catch-up immunization programme
2008 Introduction of Hib containing Pentavalent Vaccine
2009 Introduction of live JE vaccine to the EPI
2011 Revision of the National Immunization Schedule;
♦ Introduction of MMR vaccine 1st dose at 1 year of age
♦ Introduction of MMR vaccine 2nd dose at 3 years of age
♦ live JE vaccine at 9 months of age
Treatment of anaphylaxis at Field Immunization Clinic Settings
The vaccine recipient with suspected anaphylaxis should never be left alone. Ob￾tain help from those who are around and arrange transport of the patient to the
nearest hospital immediately with the clear airway. If the vaccine recipient is con￾scious he/she should be kept supine with the feet raised higher than the head. If
the patient is unconscious he/she should be kept in the left lateral position.
Adrenaline is the most important and effective drug in the treatment of anaphy￾laxis. Complications and death could be prevented by giving this drug as soon as
possible.
Adrenaline 1:1000 solution should be given intra muscular (IM). It should
NEVER be given subcutaneous (SC) or intravenous (IV).
It should be given IM into the middle 1/3 of the anterolateral aspect of the thigh
Dosage of adrenaline 1:1000
Anaphylaxis among infants (less than 1 year of age) is very rare and infants
should not be given adrenaline in field clinic setting
Age Dose of Adrenaline (1:1000)
12 months to 06 years
06 years to 12 years
12 years and over
0.15 mg (0.1ml)
0.2 mg (0.2ml)
0.3 mg (0.3ml)
Cause –specific
Type of AEFI
Definition
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 de￾fect-related reaction
An AEFI that is caused or precipitated by a vaccine that
is due to one or more quality defects of the vaccine prod￾uct 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, prescribing or
administration and thus by its nature is preventable.
Coincidental event An AEFI that is caused by something other than the
vaccine product, immunization error or immunization
anxiety .
Immunization anxi￾ety-related reaction
An AEFI arising from anxiety about the immunization.
Immunization Errors (Programme Errors) leading Adverse Events Fol￾lowing Immunization
AEFI
HB
Immunization error Adverse Event
Non sterile injections:
♦ Contaminated vaccine or diluents.
♦ Reuse of reconstituted vaccine at
subsequent session.
Infection [ e.g. local suppuration at
injection site, abscess, cellulites, sys￾temic infection, sepsis, toxic shock
syndrome, transmission of blood
borne virus (HIV, Hepatitis B or
Hepatitis C) ].
Vaccine prepared incorrectly:
♦ Vaccine reconstituted with incor￾rect diluents
♦ Drugs substituted for vaccine or
diluents
Local reaction or abscess due to
inadequate shaking of vaccine vial..
Effect of drugs (e.g. Insulin, muscle
relaxant) ,used by mistake , instead
of vaccine or diluents.
Vaccine injected at wrong site:/
route
♦ Use of subcutaneous route instead
of intradermal for BCG
♦ Use of subcutaneous route instead
of intramuscular for toxoid vac￾cines (DPT, DT, TT)
♦ Injecting into buttocks
Local reaction or injection site ab￾scess.
Sciatic nerve damage.
Ineffective vaccination .
Vaccine transported or stored incor￾rectly
Increased local reaction from frozen
vaccine and ineffective vaccination.
Ineffective vaccination
Contraindications ignored Avoidable serious vaccine reaction
s
a. Injection site abscess
b. BCG lymphadenitis
c. Severe local reactions

2. Central Nervous System Adverse events
a Vaccine derived paralytic poliomyelitis (within 4-30 days of OPV)
b. Guillen_Barre syndrome (within 30 days after immunizations)
c. Encephalopathy (within 72 hours after vaccination)
d. Encephalitis (within 1- 30 days after vaccination)
e. Meningitis (within 1-30 days after immunization)
f. Seizures

3. Other adverse events requiring investigation
a. Anaphylactic shock
b. Persistent (more than 3 hours) inconsolable screaming
c. Hypotonic Hyporesponsive Episode
d. Osteitis/Osteomylitis (within 8-16 months of vaccination)
e. Toxic shock syndrome (within few hours of immunization)
d. Hypotonic hypo responsive episodes

4. Other adverse events not requiring investigation
a. Allergic reaction
b. Arthralgia
c. High fever (>39°C )
d. Nodule at the injection site

5. Others (Specify)
Table 5:
The “cold chain” is the name given to a system of people, equipment and devices
in place to ensure that “correct quantities of potent vaccine” are procured, stored
and transported in correct temperature, until it reaches the recipients, from the
time of production.
All vaccines lose their potency when exposed to higher temperatures than recom￾mended. Some vaccines lose their potency when they are exposed to sub zero
temperature. Therefore use of potent vaccine stored and transported in correct
temperature, remains an integral part of the success of the immunization pro￾gramme. High levels of immunization coverage become meaningless if the vac￾cines used are not potent.
Figure 1 illustrates the entire cold chain system. There are many steps between
the manufacturer of the vaccine and recipients in need of immunization. Vaccine
must stay at the correct temperature throughout the entire cold chain system:
when it is transported, when it is stored in a refrigerator/ cold room, and in a
vaccine carrier until it is used at an immunization session.
Figure 14 :Cold chain system
The three essential elements of the vaccine cold chain system are:
♦ persons who manage vaccine distribution,
♦ equipments used to store and transport vaccine,
♦ devices used to monitor temperature.
Health staff managing the immunization programme remain an extremely impor￾tant link of the cold chain. Even if the finest and modern equipments and devices
are available, the cold chain will not be effective, if persons who handle them are
not using these equipments and devices properly.
The basic cold chain equipment includes:
♦ cold rooms and refrigerators used for vaccine storage,
♦ freezers used to freeze ice packs,
cold boxes, vaccine carriers, and cold packs used for vaccine transport,
♦ thermometers, Vaccine Vial Monitors (VVM), data lodgers and freeze tags
used for temperature monitoring,
♦ vehicles used for transportation of vaccines.
Vaccine Stock Management
In the national EPI vaccine handling occurs at four main levels:
♦ central ( national) level at the Epidemiology Unit,
♦ regional ( district) level at the RMSDs,
♦ divisional level at Medical Officer of Health ( MOH) and medical insti￾tutions,
♦ immunization clinics.
Transport of vaccines to the field clinics
♦ Vaccine stocks should be distributed to the clinic centers packed in vac￾cine carriers with cool packs.
♦ Vaccine carriers should be used even when the clinic is held in a room
adjoining the storage point.
♦ The correct number of cold packs should be used to maintain the cold
life of the vaccine during transport to and from the clinic and duration
of the clinic.
♦ The vaccine carrier should be taken close to the refrigerator while packing it
The vaccine should be packed immediately after removal from the re￾frigerator ,
♦ The vaccine carriers should be in good condition i.e.
• the walls are not cracked ,
• handles are not broken,
• clasps of the lid are not broken,
• lid closes tightly ,
• each cold box and vaccine carrier has the full set of ice packs,
• they are washed, dried and kept open for complete drying after
each use,
• inventory is checked annually,
• any problems brought to the notice of relevant officers.
At the clinic centre
Unopened vials of vaccine should NOT be taken out of the vaccine carrier till
ready for use. All open live vaccine (Measles, rubella, MMR,) vials should be kept
in a container with contact ice cubes or inside the form pad of the vaccine car￾rier. All the open killed/inactivated vaccine vials (DPT, Pentavalent, Hepatitis B,
DT, aTd, TT) could be kept in the form pad or on the clinic table and should not
be in contact with ice. All the vaccine should be placed away from direct sun light.

Figure 18: Keeping vaccine vials inside the foam pad
Packing of vaccines in cold boxes and vaccine carriers
♦ Ice packs should be removed from the freezer and kept outside for 20-
30 minutes until the outer layer of ice in the ice pack gets melted and
becomes water (conditioning of ice packs). Make sure that the outer
layer of the ice has become melted before using inside a cold box, vac￾cine carrier or a day carrier to transport vaccines.
♦ Place ice packs in the vaccine carriers on all sides.
COLD
Place the live vaccines and diluents at the bottom of the vaccine carrier
♦ Put all the killed vaccines into a plastic container, close the lid and keep
the container on the live vaccines in the vaccine carrier.
♦ If cubes of ice are used they should be packed in a bag.
♦ Place cubes of ice on top
Daily recording of temperature using thermometers
Using the VVM to monitor the quality of vaccine vials
With the invent of the vaccine vial monitor (VVM) cumulative heat exposure of a
vaccine vial can now be monitored with the help of the VVM. which can be
found on all WHO prequalified vaccines.
A heat sensitive square within a circle changes colour under the combined influ￾ence of heat and time. If, after exposure to heat for a certain period of time, the
square reaches the same colour of the circle or becomes darker as shown below,
the vial should be discarded.
The VVM allows the user to see at any time if the vaccine vial can still be used in
spite of possible cold chain interruptions (figure 21). If necessary, health staf
Important points on use of VVMs
♦ Under circumstances where vaccines could have been exposed to excessive
heat during shipment or storage, the VVM will always indicate whether or
not the vaccine is safe for use.
♦ The VVM will only apply to the vaccine in the vial on which it appears. It
cannot be used as a proxy for other vaccines; they may have different tem￾perature sensitivities and storage history.
♦ The VVM is a useful indicator when conducting outreach activities. Even
under intermittent cold-chain conditions vaccines can continue to be used
according to the VVM status. A VVM will not, however, indicate whether a
freeze-sensitive vaccine has been frozen.
♦ The expiry date of a vial has priority over the VVM. If the expiry date is
reached, the vial should be discarded even if the VVM suggests the vial can
still be used.
♦ All health workers must know how to interpret a VVM (see Figure 20).
There are currently, four types of VVM in use – types 2, 7, 14 and 30. Each num￾ber refers to the number of days the VVM takes to reach the discard point if it is
kept at +37 ° C. Various types of VVMs are assigned to different vaccines accord￾ing to their heat sensitivity – for example, VVM type 2 is assigned to OPV which
is a very heat-sensitive vaccine, while VVM type 7 is assigned to DTP-HepB-Hib which is much less heat sensitive
Use of freeze tags to monitor exposing vaccine to freezing
The shake test
The shake test is used to determine if the vaccine has been frozen.
During the process of freezing, vaccine tends to flocculate (i.e., virus particles
stick together to form larger clumps). When a vial of vaccine which has been
frozen and then thawed is shaken and then allowed to sediment, it will sediment
more quickly than the same vaccine from the same manufacturer which has not
been frozen. Figure 25 gives a comparison between the sedimentation rates of a
frozen and a never frozen DPT vaccine.
The shake test is best conducted using a vial of vaccine which you have frozen
solid yourself and do not intend to use. This vial can be used as a frozen
“control” against which to compare vaccines in doubt. Whenever the “control”
vial sediments significantly faster than the test vial, then the test vial is acceptable.
If the sedimentation rates are the same, however, then the test vial should not be
used. Remember, the shake test can only be conducted on “test” and “control”
vials from the same manufacturer.
Figure 25: Shake tes