Immunisation

7th October 2010

Dr. Aisling N Shilleabhin

Department of Public Health and Primary Care

The Origins of Immunisation

Smallpox

Poxvirus (variola)
Highly contagious
No treatment once contracted
20 40% fatality rate (variola major)

Edward Jenner
1798: noticed that milkmaids didnt get smallpox
Reasoned that it was due to exposure to cowpox
virus
Inoculated a young boy with some cowpox virus
he didnt develop smallpox when he was
subsequently inoculated with it
Jenner called it vaccination (vacca Latin for cow)

Basic Immunology
The Immune System
Extremely complex
Involves all systems in the body
Broadly composed of:

Organs skin, spleen

Tissues lymphatic system, bone marrow
Cells white blood cells, macrophages, NK cells
Secretions mucus, tears, gastric acid, saliva
Proteins - hormones, enzymes, leukotrienes,
PGs, immunoglobulins

How Do Vaccinations Work?

Vaccination
The process of administering a killed or weakened
(attenuated) form of a disease to patients, as a
means of giving them immunity to a more serious
form of the disease
The patient develops antibodies against the
inoculated material; if the same types of
microorganisms enter the body again, they will be
destroyed by the antibodies

Immunology
The study of the bodys ability to fight disease
From the Latin immunitas freedom from

Basic Immunology
The Immune System
A. Natural (Innate) Immunity non-specific
Barriers skin and mucous membranes, with
their glands and secretions
Cells macrophages, NK cells, PMN leucocytes
They secrete interferons, lysozyme
Induce other cells to secrete acute phase
proteins, complement, histamine

A lot of flu-like symptoms e.g. weakness,

fever, inflammation, malaise are caused by
the bodys response to disease, rather than
the infecting organism itself

Basic Immunology

Rhinovirus

The Immune System

B. Acquired (Adaptive) Immunity specific
Usually innate immunity will deal with infection
Lymphocyte is most crucial component of
acquired immunity (T and B cells)
Disadvantages:
Slow; can take days or weeks
More complex so can go wrong e.g. autoimmune
disorders

Advantages:
Memory repeat infections with the same organism are
dealt with very quickly
Incredibly specific generates antibodies to any
invader it encounters

Basic Immunology
Acquired (Adaptive) Immunity
How it Works:
Invading organism (virus, bacteria etc) has proteins
on the outside of its cells ANTIGENS (Ag)
Proteins on cells of the immune system that can
interact with the antigens are called ANTIBODIES
(Ab)
Ag and Ab react to form the Ag-Ab complex
Activates the immune system to make more of the
right antibodies i.e. those that are specific for
that organism
The antibodies then stick to the antigens on the
invading cells surfaces, marking them as foreign.
The immune system then activates its mechanisms

How Do Vaccines Work?

Alternative to Active Immunity

Live (Attenuated) Vaccines

Passive Immunity

Usually viruses
Give a better immune response
Can cause a mild version of the disease
Can cause active disease in immunosuppressed patients
Risk of reverse mutation back to active form (rare)
E.g. MMR, BCG (attenuated by bile!)

Inactivated Toxins (Toxoids)

Fully antigenic but no pathogenicity
E.g. tetanus, diphtheria

Killed (Inactive) Vaccines

Ready-made Abs are injected into the patient to allow

them fight a specific disease
Lasts about 6-8 weeks
Used to be grown in horses / taken from people who
had recently been immunised
Repeated exposure to horse serum led to a reaction
to the foreign (equine) proteins serum sickness
Still used occasionally e.g. chicken pox in pregnancy
(VZIg), hepatitis B in unvaccinated patients (IVIg)

Large molecules, e.g. bacteria lots of Ags;

E.g. influenza virus, pneumococcus
Immune response not as strong, so combined with adjuvants
(e.g. aluminium salts) to strengthen reaction often need
boosters

The Irish Immunisation

Schedule

The Irish Immunisation

Schedule
Age

Age

Vaccination

Birth

BCG (Tuberculosis)

2 mths

6-in-1
PCV

4 mths

6-in-1
Meningitis C

6 mths

6-in-1
Meningitis C
PCV

Vaccination

12 mths

MMR
PCV

13 mths

Men C
Hib

PCV
Pneumococcal
conjugate vaccine

6 in 1 Vaccination
Diphtheria
Tetanus
Whooping cough
(Pertussis)
Hib (Haemophilus
influenzae b)
Polio (inactivated
poliomyelitis
Hepatitis B

Schedule Changes
Hib Booster
July 2005, National Immunisation Advisory
Committee recommended that children from
12 mths to 3 years old be given a booster
dose of Hib
This was due to several cases of Hib
meningitis in children who had been fully
vaccinated
Started in November 2005 with catch-up
injections - letters posted to parents, inviting
them to bring children of between 12 -36
months in
Hib b
t
i
ti l t ll hild

4-5 years

4-in-1
MMR

11-14 years

Td

12 yrs (females) HPV

MMR
Measles
Mumps
Rubella

4 in 1 Vaccination

Diphtheria
Tetanus
Whooping cough
Polio

Td
Tetanus
Diphtheria

Schedule Changes
Pneumococcus (Childhood)
Adult vaccine given to at risk groups once
Introduced to childhood schedule for all children
born after 1st July 08
Catch-up programme for children under 2 at that
time.
Aim to reduce pneumococcal pneumonia and
meningitis
19% Streptococcus pneumoniae bacteria in
Ireland are resistant to penicillin
S. pneunmoniae causes 50% of communityacquired pneumonia

Schedule Changes

New Vaccinations
HPV

Hepatitis B

Introduced Sept 2010 (no catch-up programme)

Introduced to childhood schedule for all

children born after 1st July 08
Part of 6-in-1 vaccine
No catch-up programme for children born
prior to that

This year, all girls in 1st / 2nd year of second-level schools

vaccinated
After this year, all girls turning 12 between Sept and Aug
of that academic year will be vaccinated

3 doses at 0, 2, and 6 months

Non-live vaccine
Contains 4 types of HPV 6, 11, 16, 18

HPV is a common virus. Around 40 types can be

sexually transmitted and causes genital warts and
cervical cancer
Types 16 and 18 cause 70% of cervical cancer
Types 6 and 11 cause 90% of genital warts
Vaccine most effective if given before exposure (i.e.
before onset of sexual activity)

New Vaccinations

Why Bother?

HPV
Pros
Safe side fx generally minor

1/10: Pyrexia, erythema / pain / swelling at injection site

1/1,000-1/10,000: Urticaria
<1/10,000: Bronchospasm; ?Guillain-Barr Syndrome?
Syncope is common (mainly d/t age-group)

Effective 99% effective in preventing pre-cancerous

lesion d/t HPV 16 and 18

Concerns
That it will promote early onset sexual activity (no
evidence)
New drug, only limited follow-up available
Sh

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Tuberculosis

Diphtheria

Disease
Mycobacterium tuberculosis
Usually affects lungs
(consumption), but can affect
other organs
Droplet spread
7% death rate (usually elderly)
Treatment: antibiotics for
minimum 6 months!
Several outbreaks in recent yrs
MDRTB now emerging

Vaccination
Live attenuated; lasts ~ 15 yrs
50% effective (70-80% v. TB
meningitis and miliary TB)
Little evidence of effectiveness
>16 y.o.
Mantoux test

Diphtheria
Corynebacterium
diphtheriae
Severe sore throat and
swelling of tonsils
Droplet spread
Produces a toxin that can
damage heart muscle
Can cause complete
airway obstruction and
death in worst cases (1 in
15 die)
Vaccination gives 95%
protection

Tetanus
Tetanus

Whooping Cough (Pertussis)

Disease

Toxin of Clostridium
tetani (bacteria)
Causes muscle
spasm and rigidity;
10-25% death rate
Forms highly resistant
spores, found in soil,
etc.
No cure, just
supportive treatment
until recovery
Booster should be
given every 10 years

Bordatella pertussis
Characteristic cough,
risk of encephalitis
Very severe if < 6
mths
Lasts 8 weeks, no tx

Vaccination
Acellular used in Eire
Controversy in
1970s over
neurological

Polio

Meningitis
Disease

Disease
Polio virus
Faecal-oral and
droplet spread
95% asymptomatic /
mild flu-like illness
2% flaccid paralysis

Vaccination
IPV (Salk inactive)
OPV Sabin live
attenuated (sugar
cubes)

Inflammation of the lining

of the brain
High fatality, esp. if
septicaemia
Most severe form due to
Neisseria meningitidis

Vaccination
Protects against
Neisseria meningitidis
type C (40%) can still
get A/B
Pneumovax
Men C notified cases:
2000 139; 2005 5

Measles
Disease
Measles virus
Catarrh, conjunctivitis,
rash, misery, fever, cough
Incredibly contagious
Complications ear
infxns, pneumonia,
encephalitis
1/2000 die

Vaccination
Live attenuated; gives
90% protection

Mumps
Disease
Paramyxovirus
20-30% asymptomatic
Inflammation of the
salivary glands esp the
parotid gland
Complications orchitis,
pancreatitis, encephalitis,
deafness
No specific tx

Vaccination
Live attenuated; 90%
ff i

Rubella

MMR Vaccination

Disease

Controversial

Rubella virus
German measles - like mild
measles infection
Main risk is to pregnant
women 25% of babies
born with birth defects if
Mum infected during
pregnancy (congenital
rubella deafness, heart
defects, microcephaly, LD,
cataracts)

Introduced in 1985. Uptake initially good and

measles, mumps and rubella cases fell
Wakefield study (Lancet 1998) suggested a link
between MMR and autism
Huge drop off in uptake of MMR
Measles outbreak in 2000 1603 cases, 3 babies
died
Study since totally discredited, but uptake of MMR
has been slow to bounce back (was as low as
69% - 2001)
Current uptake levels at about 90% countrywide
Need 95% uptake to protect population (herd

Vaccination
Live attenuated; 95%

Herd Immunity

Herd Immunity

What is it?

What is it?

Vaccinated people act as a sort of

"firewall" in the spread of the
disease. Since the protection offered
by vaccines is rarely 100%, the
vaccine will be more effective if
more people have been vaccinated.
This is because the disease may be able to jump
from one unvaccinated person to another person who
has not been vaccinated, but is unlikely to be able to
jump from one unvaccinated person to another who
h b
i t d

Why Should I have My Child

Vaccinated?
Benefit to the Community
Herd immunity
Protects those children who havent been
vaccinated yet (e.g. those <1 y.o. in the case of
MMR)
Protects those children who cant be vaccinated
for medical reasons (e.g. undergoing cancer
treatment, immune disorders, allergy to vaccine
components)
Protects those who dont respond to the vaccine
Problem: not a very persuasive argument for
parents worried about their child

f th di

For measles, we need 95% vaccination uptake to

achieve herd immunity, because it is so
t i

Risks of Vaccination V. Disease

Vaccination Reactions
Common
Pain at injection site
Fever

Unusual
Convulsion (usually febrile) (1/1000)
Prolonged crying after injection (1/100) esp
DTP
Abscess formation at site of injection esp
BCG

Rare

Benefit to the Individual

Ri k

Therefore, when a certain percentage of a

population is vaccinated, the spread of the
disease is effectively stopped. This critical
percentage depends on the disease and the
vaccine. This is herd immunity - the fact that
others in the herd or population have been
vaccinated provides protection to all others,
whether or not vaccinated themselves.

i h th

i k

f th

Anaphylactic reaction (1/100,000)

Risks of Vaccination V. Disease

Specific MMR Vaccination Reactions
Mini-measles
Fever and rash 7-10 days after the injection

Mini-mumps
Fever and mild parotid gland swelling 3-4
weeks after the injection

Rash
Bruise-like spots all over the body, anytime in
the first 6 weeks after MMR (very rare)

No known deaths due to vaccination

Persuasive Arguments
Why not give single vaccinations
It takes longer, so the baby is at risk of infection
for longer
Would mean babies are given far more injections
Single vaccines have not undergone the same
rigorous testing as combined vaccination
The current vaccines are known to be safe

Its too much for a babys immune system

Babies are exposed to foreign antigens every day
through eating, getting simple head colds etc. The
number of antigens in vaccinations is not
significantly different from this

Risks of Vaccination V. Disease

Disease Risks
Measles
Pneumonia 1/25, Encephalitis 1/1000, Death
1/2000
SSPE 1/8000 (doesnt occur in vaccination)

Mumps
Encephalitis 1/300

Infertility

Rubella
Congenital Rubella Syndrome (if pregnant)

Diphtheria: Death 1/20

Pertussis
Pneumonia 1/20, Encephalitis 1/1000, Death

Persuasive Arguments
I didnt have any vaccinations - Im fine!
The development of vaccinations has moved on:
they just werent available previously
The risks of getting the disease still outweigh the
risks of vaccination
The only way to eventually eradicate these
diseases is by vaccination

Doctors just recommend vaccinations so

they get paid by the government
Doctors are parents too the vast majority
vaccinate their children

The Potential of Immunisation

WHO Smallpox Eradication Programme
1967: smallpox still endemic in 30
countries
1015 million cases p.a.; 2 million deaths
p.a.
Humans only host organism
WHO aimed to eradicate the disease
through a programme of mass vaccination
aiming for 100% of the population
In fact it was the balance of high
vaccination rates (approx 80%) and early

The Potential of Immunisation

WHO Eradication Programme 1967
1977: last case of smallpox reported in
Somalia
1978: WHO announced the eradication of
smallpox the first and only major human
disease to have been eradicated
Programme described as a triumph of
management, not of medicine
The US and Russian governments (+
others??) still hold stocks of smallpox virus
for potential biological weapon use.

The Future
Efforts to Find New Vaccines
Malaria
HIV

Eradication of More Diseases

Polio and diphtheria most likely, maybe measles

Proper Vaccination Programmes in the

Developing World
Info: www.immunisation.ie

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