Immunization

Dr Rasha salama
PhD. Community medicine
Suez Canal University
Egypt
 Immunity

Specific defenses
Immunity

Active immunity Passive immunity

Following clinical infection natural Transfer of maternal

Antibodies Through placenta

Following subclinical infection Transfer of maternal

Antibodies Through milk
acquired
Following vaccination Following administration of
Immunoglobulin or antiserum
 Active immunity
• Resistance developed in response to
stimulus by an antigen (infecting agent or
vaccine) and is characterized by the
production of antibodies by the host.
 Passive immunity
• Immunity conferred by an antibody
produced in another host. It may be
acquired naturally or artificially (through an
antibody-containing preparation).
 Immunizing agents

Immunizing agents

vaccines immunuglobulins antisera

Immunoglobulins

• There are 5 major classes: IgM, IgA, IgG,

IgE, IgD.
• Two types of immunoglobulin preparations
are available for passive immunization:
– Normal human immunoglobulin
– Specific (hyper-immune) human
immunoglobulin
 Antisera or antitoxins
• These are materials prepared in animals
or non human sources such as horses.
 Immunoglobulin and antiserum

Human normal Human specific Non human ig

immunoglobulin immunoglobulin (antisera)
Hepatitis A Hepatitis B Diphtheria
Measles Varicella Tetanus
Rabies Diphtheria Gas gangrene
Tetanus Botulism
Mumps Rabies
 Vaccination

• Vaccination is a method of giving antigen to

stimulate the immune response through
active immunization.

• A vaccine is an immuno-biological substance

designed to produce specific protection
against a given disease.
• A vaccine is “antigenic” but not “pathogenic”.
 Types of vaccines
• Live vaccines
• Attenuated live vaccines
• Inactivated (killed vaccines)
• Toxoids
• Polysaccharide and polypeptide (cellular
fraction) vaccines
• Surface antigen (recombinant) vaccines.
 Live vaccines
• Live vaccines are made from live
infectious agents without any amendment.
• The only live vaccine is “Variola” small pox
vaccine, made of live vaccinia cow-pox
virus (not variola virus) which is not
pathogenic but antigenic, giving cross
immunity for variola.
Live attenuated (avirulent) vaccines
• Virulent pathogenic organisms are treated to
become attenuated and avirulent but antigenic.
They have lost their capacity to induce full-blown
disease but retain their immunogenicity.
• Live attenuated vaccines should not be
administered to persons with suppressed
immune response due to:
– Leukemia and lymphoma
– Other malignancies
– Receiving corticosteroids and anti-metabolic agents
– Radiation
– pregnancy
 Inactivated (killed) vaccines
• Organisms are killed or inactivated by heat
or chemicals but remain antigenic. They
are usually safe but less effective than live
attenuated vaccines. The only absolute
contraindication to their administration is a
severe local or general reaction to a
previous dose.
 Toxoids

• They are prepared by detoxifying the exotoxins

of some bacteria rendering them antigenic but
not pathogenic. Adjuvant (e.g. alum
precipitation) is used to increase the potency of
vaccine.

• The antibodies produces in the body as a

consequence of toxoid administration neutralize
the toxic moiety produced during infection rather
than act upon the organism itself. In general
toxoids are highly efficacious and safe
immunizing agents.
Polysaccharide and polypeptide
(cellular fraction) vaccines

• They are prepared from extracted cellular

fractions e.g. meningococcal vaccine from the
polysaccharide antigen of the cell wall, the
pneumococcal vaccine from the polysaccharide
contained in the capsule of the organism, and
hepatitis B polypeptide vaccine.

• Their efficacy and safety appear to be high.

Surface antigen (recombinant)
vaccines.
• It is prepared by cloning HBsAg gene in
yeast cells where it is expressed. HBsAg
produced is then used for vaccine
preparations.

• Their efficacy and safety also appear to be

high.
 Types of vaccines
Live Live Killed Toxoids Cellular fraction Recombinant
vaccines Attenuated Inactivated vaccines vaccines
vaccines vaccines

•Small pox •BCG •Typhoid •Diphtheria •Meningococcal •Hepatitis B

variola •Typhoid •Cholera •Tetanus polysaccharide vaccine
vaccine oral •Pertussis vaccine
•Plague •Plague •Pneumococcal
•Oral polio polysaccharide
•Rabies vaccine
•Yellow •Salk polio
fever •Hepatitis B
•Intra- polypeptide
•Measles muscular vaccine
•Mumps influenza
•Rubella •Japanise
•Intranasal encephalitis
Influenza
•Typhus
 Routes of administration
• Deep subcutaneous or intramuscular route
(most vaccines)
• Oral route (sabine vaccine, oral BCG
vaccine)
• Intradermal route (BCG vaccine)
• Scarification (small pox vaccine)
• Intranasal route (live attenuated influenza
vaccine)
 Scheme of immunization
• Primary vaccination
– One dose vaccines (BCG, variola, measles,
mumps, rubella, yellow fever)
– Multiple dose vaccines (polio, DPT, hepatitis B)
• Booster vaccination
To maintain immunity level after it declines after
some time has elapsed (DT, MMR).
Periods of maintained immunity
due to vaccines
• Short period (months): cholera vaccine
• Two years: TAB vaccine
• Three to five years: DPT vaccine
• Five or more years: BCG vaccine
• Ten years: yellow fever vaccine
• Solid immunity: measles, mumps, and
rubella vaccines.
 Levels of effectiveness
• Absolutely protective(100%): yellow fever
vaccine
• Almost absolutely protective (99%): Variola,
measles, mumps, rubella vaccines, and
diphtheria and tetanus toxoids.
• Highly protective (80-95%): polio, BCG, Hepatitis
B, and pertussis vaccines.
• Moderately protective (40-60%) TAB, cholera
vaccine, and influenza killed vaccine.
 The Cold Chain
• The "cold chain" is a system of storage
and transport of vaccines at low
temperature from the manufacturer to the
actual vaccination site.
• The cold chain system is necessary
because vaccine failure may occur due to
failure to store and transport under strict
temperature controls.
 The Cold Chain Equipment
Cold chain equipment consists of the following:

(a) Walk in cold rooms: They are located at

regional level, meant to store vaccines up to 3
months and serve districts.
(b) Deep freezers (300 ltr) and Ice lined
Refrigerators: supplied to all districts and the
WIC locations to store vaccines. Deep freezers
are used for making ice packs and to store OPV
and measles vaccines.
(c) Small deep freezers and ILR (140 ltr) : One
set is provided to PHCs, and Family Planning
Centers
• (d) Cold boxes: Cold boxes are supplied to all
peripheral centers. These are used mainly for
transportation of the vaccines.
• (e) Vaccine carriers: Vaccine carriers are used
to carry small quantities of vaccines (16-20 vials)
for the out of reach sessions. 4 fully frozen ice
packs are used for lining the sides, and vials of
DPT, DT, TT and diluents should not be placed
in direct contact with frozen ice packs. The
carriers should be closed tightly.
• (f) Ice packs: The ice packs contain water and
no salt should be added to it.
• Among the vaccines, polio is the most
sensitive to heat, requiring storage at
minus 20 degree C.
• Vaccines which must be stored in the
freezer compartment are : polio and
measles.
• Vaccines which must be stored in the
COLD PART but never allowed to freeze
are : typhoid, DPT, tetanus toxoid, DT,
BCG and diluents
HAZARDS OF IMMUNIZATION
• No immune response is entirely free from the
risk of adverse reactions or remote squeal.
The adverse reactions that may occur may be
grouped under the following heads:

1. Reactions inherent to inoculation

2. Reactions due to faulty techniques
3. Reactions due to hypersensitivity
4. Neurological involvement
5. Provocative reactions
6. Others
• 1. Reactions inherent to inoculation:
These may be local general reactions. The local
reactions may be pain, swelling, redness,
tenderness and development of a small nodule
or sterile abscess at the site of injection.
• The general reactions may be fever, malaise,
headache and other constitutional symptoms.
Most killed bacterial vaccines (e.g., typhoid)
cause some local and general reactions.
Diphtheria and tetanus toxoids and live polio
vaccine cause little reaction.
• 2. Reactions due to faulty techniques:

Faulty techniques may relate to

• faulty production of vaccine (e.g. inadequate inactivation of the
microbe, inadequate detoxication),
• too much vaccine given in one dose,
• improper immunization site or route,
• vaccine reconstituted with incorrect diluents,
• wrong amount of diluent used,
• drug substituted for vaccine or diluent,
• vaccine prepared incorrectly for use (e.g., an adsorbed vaccine not
shaken properly before use),
• vaccine or dliluent contaminated,
• vaccine stored incorrectly,
• contraindications ignored (e.g. a child who experienced a severe
reaction after a previous dose of DPT vaccine is immunized with he
same vaccine),
• reconstituted vaccine of one session of immunization used again at
the subsequent session.
• Use of improperly sterilized syringes and
needles carry the hazard of hepatitis B
virus, and staphylo - and streptococcal
infection
• 3. Reactions due to hypersensitivity:

• Administration of antisera (e.g., ATS) may occasionally

give rise to anaphylactic shock and serum sickness.
Many viral vaccines contain traces of various antibiotics
used in their preparation and some individuals may be
sensitive to the antibiotic which it contains. Anaphylactic
shock is a rare but dangerous complication of injection of
antiserum. There is bronchospasm, dyspnoea, pallor,
hypotension and collapse.

• The symptoms may appear within a few minutes of

injection or may be delayed up to 2 hours. Some viral
vaccines prepared from embryonated eggs (e.g.,
influenza) may bring about generalized anaphylactic
reactions. Serum sickness is characterized by symptoms
such as fever, rash, oedema and joint pains occurring 7 -
12 days of injection of antiserum.
• 4. Neurological involvement:
• Neuritic manifestations may be seen after the
administration of serum or vaccine. The well-
known examples are the postvaccinial
encephalitis and encephalopathy following
administration of anti -rabies and smallpox
vaccines.
• GuillainBarre syndrome in association with the
swine influenza vaccine is another example.
• 5. Provocative reactions:
• Occasionally following immunization there may
occur a disease totally unconnected with the
immunizing agent (e.g., provocative polio after
DPT or DT administration against diphtheria).
• The mechanism seems to be that the individual
is harboring the infectious agent and the
administration of the vaccine shortens the
incubation period and produces the disease or
what may have been otherwise only a latent
infection is converted into a clinical attack.
• 6. Others:
• These may comprise damage to the fetus
(e.g., with rubella vaccination);
displacement in the age-distribution of a
disease (e.g., a potential problem in mass
vaccination against measles, rubella and
mumps).
PRECAUTIONS TO BE TAKEN
• Before administration of the antiserum or
antitoxin, it is necessary to test for sensitivity
reaction. This can be done in 2 ways:
(a) instilling a drop of the preparation into the
conjunctival sac. A sensitized person will
develop pricking of the conjunctiva.
(b) a more reliable way of testing is by intradermal
injection of 0.2 ml of antiserum diluted 1 : 10 with
saline. A sensitized patient will develop a wheal
and flare within 10 minutes at the site of
injection. It should be borne in mind that these
tests are not infallible.
• Adrenaline (1: 1000 solution) should be kept ready when
giving foreign serum. In the event of anaphylaxis, for an
adult, 0.5 ml of adrenaline solution should be injected
intramuscularly immediately, followed by 0.5 ml every 20
minutes if the systolic blood pressure is below 100 mm
of mercury.
• An injection of antihistaminic drug should also be given,
e.g., 10-20 mg of chlorpheniramine maleate by the
intramuscular route, to minimise the after-effects such as
urticaria or oedema. The patient should be observed for
30 minutes after any serum injection.
• The risk of adverse reactions can be reduced by proper
sterilization of syringes and needles, by proper selection
of the subject and the product, and if due care is
exercised in carrying out the procedure. Measles and
BCG vaccines should be reconstituted only with the
diluent supplied by the manufacturer.
• Reconstituted vaccine should be discarded at the end of
each immunization session and NEVER retained for use
in subsequent sessions. In the refrigerator of the
immunization centre, no other drug and substances
should be stored beside vaccines.
• Training of immunization worker and their close
supervision to ensure that proper procedures are being
followed are essential to prevent complications and
deaths following immunization.
 Vaccination Coverage
• Vaccination coverage is the percent of at
risk or susceptible individuals, or
population who have been fully immunized
against particular diseases by vaccines or
toxoids. To be significantly effective in
prevention of disease on mass or
community level at least a satisfactory
proportion (75% or more) of the at risk
population must be immunized.
Ways of achieving satisfactory
immunization coverage
• Efficient immunization service; urban and rural

• Health awareness and cooperation of the public

• Periodic mass immunization campaigns, to cover

those who missed regular immunizations

• Outreach programs in rural and nomad areas, and

home visits
 Application of active immunization
• Infants and children expanded immunization
program (schedule)
• Active immunization for adult females
• Vaccination for special occupations
• Vaccination for special life styles
• Vaccination for special environmental situations
• Vaccinations for special health status persons
• Vaccinations in travel
• Vaccines against bioterrorism
Compulsory (obligatory) vaccination for
infants, and booster vaccination for
children (Expanded immunization
program)

• See local schedule of vaccination

• Note (children failing to complete

childhood vaccination schedule)
Active immunization for adult
females
• MMR vaccine is given in adolescence before or after
marriage, but not during pregnancy and has to be before
3 months of conception

• Tetanus toxoid in pregnancy to prevent tetanus

neonatorum in the newborn. In the first pregnancy on the
third month and after 1 month. The third dose in the
second pregnancy, and the fourth on the third pregnancy
with a maximum of 5 doses. If 10 years elapse, and then
pregnancy occurs, the doses are given from the start.

• Live attenuated vaccines should not be given during

pregnancy.
Vaccination for special occupations

• Health care workers: hepatitis B, influenza, MMR, polio

• Public safety personnel (police, fire fighters) and staff of
institutions for the developmentally disabled: hepatitis B,
influenza
• Vets and animal handlers: rabies, plague and anthrax
• Sewage workers: DT, hepatitis A, polio, TAB
• Food handlers: TAB
• Military troops and camp dwellers: pneumococcal,
meningococcal, influenza, BCG (for non reactors), tetanus
Vaccination for special life styles and
special environmental situations
• Homosexually active males, Heterosexual
with promiscus sexual partner specially who
has STDs, and Injecting drug users
• Inmates of long term correctional institutes,
residents of institutions for the
developmentally disabled, and household
contacts of HBV carriers or patients
All should receive hepatitis B vaccine
Vaccinations for special health
status persons
• Immuno-compromised persons ( Leukemia,
lymphoma, HIV, malignancy…)
• Hemodialysis and transplantation
Should receive the following vaccines
according to their situation:
HBV, Influenza, Pneuomococcal vaccines
Vaccinations in travel

• Varies according to the country of arrival and

departure.
– Primary vaccine series
– Continuation of booster doses
– Specific vaccine according to the country traveled to:
• TAB, YF, cholera, meningiococcal, pneuomococcal, HIB,
influenza, rabies, plague, Japanese encephalitis.
• Haj for instance necessates meningococcal vaccination from
all over, and YF from places like south Africa, and cholera
from places like India.
Vaccines against bioterrorism

• Anthrax
• Small pox
• plague
 New approaches
• Schistosomiasis
• Cancer
• HIV/AIDS
• Malaria
Vaccine surveillance and testing
“monitoring vaccine effectiveness”
Through:
• Randomized field trials
• Retrospective cohort studies
• Case-control studies
• Incidence density measures
Randomized field trials
– The standard way to measure the
effectiveness of a new vaccine introduced.
– In this type of trial, susceptible persons are
randomized into two groups and are then
given the vaccine or the placebo
– The vaccinated and the unvaccinated are
followed through the high risk season of the
year
 Randomized field trials (cont.)
• The attack rate (AR) is then determined in each
group:
Number of persons ill
• AR =
Number of persons exposed to the disease

• next the vaccine effectiveness (VE) is calculated:

AR (unvaccinated) - AR (vaccinated)
VE = X 100
AR (unvaccinated)
 Retrospective cohort studies
• The antigenic variability of influenza virus
necessitates frequent (often yearly)
changes in the constituents of the vaccine
to keep them up date with the new strains.
Retrospective cohort studies are thus done
to evaluate the protective efficacy of the
vaccines.
Case-control studies
• Done because randomized control trials
are very costly.
AR (vaccinated)

• VE = 1- = (1- RR) or (1- OR)

AR (unvaccinated)
 Incidence density measures
• They are used to determine the the
optimal timing for administration of a new
vaccine and the duration of the immunity
produced. It has the following formula:
Number of new cases of a disease
• ID = Person-time of exposure (days, weeks, months, years..)
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