IMMUNISATION PRACTICE

Dr E O D ADDO-YOBO MD, MWACP, FGCPS, MSc, DTCH

Dept of Child Health,
KNUST-SMS/KATH,
Kumasi, Ghana
2011-12
Outline

Basic Principles of Immunisation &
Terminology

Routine EPI vaccines

Other vaccines

New vaccines

General Issues:
◦ Vaccine Reactions
◦ Immunization Safety Issues
◦ Contraindications
◦ Immunization in Special situations
 What is Immunisation?

Immunisation:
The biological process of conferring protection (artificially) in a human host
against infectious agents in the environment .

Vaccination:
The act or practice of inducing in a non-immune person a primary response
such that on first contact with the corresponding pathogen, a rapid secondary
(memory response) is mounted, leading to prevention of disease symptoms.

Vaccine:
suspension of attenuated or killed micro-organisms or fractions thereof (i.e.
purified protein sub-units, polysaccharides, conjugated PSs, or split virions …)
administered (orally, in, id, im, sc) to induce specific immunity and prevent
infectious disease – prophylactic (i.e; EPI vaccines & therapeutic vaccines - i.e.
cancer vaccines in development)

Major component of Child Survival Strategies

Battle for survival!

infection, immune
pathogen
toxins disease & response
(human) or death
Complications
/disability

vaccine protective immune responses

without majors adverse events
The Principles of Immunization

To prime recipient’s immune response

To generate B and T memory cells

Toheighten immune response (humoral and cell
mediated) to pathogens

Vaccine(s) should
◦ have minimal adverse effects
◦ prevent/reduce severity of infectious diseases
(effectiveness)
◦ be of assured quality and available for general use
Structure of the Immune System

Substances, Cells, Tissues and Organs in different

locations (central and peripheral)

Complement each other in protecting the body

Main organs include skin, spleen, thymus, and lymph

nodes.

Freely mobile cells from bone marrow, blood and

lymphatics.
Important Definitions

Immune response
Development of resistance/immunity to a foreign substance eg. infectious
agent.
Can be humoral (Ab) or cell mediated (lymphoid) or both.
T & B lymphocytes, tolerance, hypersensitivity, immunodeficiency

Immunity
The properties of host that confer resistance to a specific infectious agent.
(The ability of the body to protect itself against disease causing organisms)
Can be natural or acquired.

Natural Immunity - not acquired through contact with infectious agent.

Acquisition of Immunity

Natural acquisition of immunity:
from infection with the microbe in nature, e.g. measles
resulting in protection from future exposure (note
notion of prior exposure)

Artificial immunity: vaccine or immunoglobulin

administration
◦ Vaccine: organism or toxin, either killed or live but attenuated
(organism) or inactivated (toxin). Live vaccines (BCG, polio,
measles); killed vaccines (pertussis, polio), toxoids (tetanus,
diphtheria), subunit (hep B).

Passive immunity: from mother or Ig infusions

Immunization process

Administration of vaccine:
Potent immune response in a few weeks, several
injections for some (DPT),
some one shot (measles).
Booster doses may be necessary (Hep. B).

Vaccines are safe, side effects (AEFI) rarer

than complications of disease prevented.
Vaccines are fragile (storage).

AEFI: hypersensitivity, human errors (poor or

absent training, or level).
 Antibody Response following exposure to antigen

IgG Response

IgM Response

0
30 60
3rd Time 1 yr. 10 yrs
Primary encounter Secondary
Types of immunity

Non-specific (primary/innate):
First line defense, does not require prior exposure

Specific (adaptive):
Requires prior exposure,
hallmarks (memory, specificity, recognition of self and
non-self), antigen- antibody
 Secondary, Acquired
Similarities between vaccines and other
drugs

Vaccines are also medicines

Potential for adverse effects

Multiple ingredients

Potentialfor interaction with disease and other
medicines

Also need to comply with standards of safety, efficacy
and quality
 Categorization of current vaccines

Live attenuated:
◦ Viruses (oral polio, measles, mumps, rubella, yellow fever),
◦ Bacteria (BCG, cholera)- long lasting immunity, very fragile (cold
chain), mutation to pathogenicity

Killed vaccines:
◦ Viruses (hep. A, Salk polio), bacteria (pertussis, cholera)-
intermediate immunity, several doses may be required

Sub-unit vaccines including toxoids:

◦ Tetanus, Hep. B, acellular vaccines, conjugate polysacharide vaccines
linked with suitable carrier proteins (Hib). Also single or polyvalent
vaccines.
ROUTE OF ADMINISTRATION

Essence of Route: Elicit Immune Response with
minimal risk

Deep IM for vaccines with adjuvants (depot
effect, less granuloma formation)

Intradermal (ID) - better for live vaccines, e.g.
BCG

Intranasal influenza vaccine – increased risk of
Bell’s Palsy reported

New routes may have other safety risks
 Who needs to be immunised?
immunised?

High risk groups

Young children

Elderly

Malnourished
 Leading causes of early childhood
vaccine--preventable deaths
vaccine
1. Pneumococcal 28%
2. Measles 21%
3. Rotavirus 16%
72% of 2.5m VPD deaths 4. Hib 15%

WHO/FCH/IVB/VAM, JUN04 (<5y, 2002 data)

can be prevented with 5
5. Pertussis 12%
vaccines
6. Tetanus 8%
7. Yellow Fever <1%
rota
8. Diphtheria <0.5%
9. Poliomyelitis <0.5%
10. Meningococcal <0.5%
Immunisation schedule for Ghanaian children:
Expanded Programme on Immunisation (EPI)

Age Vaccines
Birth BCG OPV 0
6 weeks DPT/HepB/Hib 1 OPV 1

10 weeks DPT/HepB/Hib 2 OPV 2

14 weeks DPT/HepB/Hib 3 OPV 3

6 months Vit A
9 months Measles Yellow fever
12 months Vit A
Common Vaccine Types & Characteristics

EPI VACCINES

 Tuberculosis
 Poliomyelitis
 Diphtheria, Tetanus, Pertussis
 Hep B
 Measles, Mumps, Rubella
 Hib
 Yellow Fever
BCG (Baccillus Calmette Guérin)
Guérin) -1

Disease = Tuberculosis

Organism: Mycobacterium tuberculosis or M. bovis.

Non-sporing, rod-shaped, acid-fast bacillus (neither gram positive or gram
negative)

Vaccine: Live attenuated, freeze-dried

Storage 2oC - 8oC. Never frozen.
Do not shake to mix. Use with 2 hours.
Shelf life 12 - 18 months.

Vaccine Efficacy: 0 – 80% for PTB; 75-86% for Miliary and TB meningitis

Indications:

People at risk - infants, health personnel, contacts with sputum +ve cases.

If exposure suspected, tuberculin test first then immunise.

With contact: tuberculin test, repeat after 6 months, if positive =>
seroconversion, hence chemoprophylaxis.

Duration of immunity – unknown. Evidence that wanes with time

[Tuberculin ]
Both Mantoux and Heaf = Purified Protein Derivative (PPD).

PPD = heat treated products of growth and lysis of

mycobacterium.

Results read 48 - 96 hours later.

Positive result = induration of 5 mm in dia. with 0.1 ml 1 in

1000 dil. (If less => negative)

Heaf gun: 5-14 mm = Heaf Grade 2

≥ 15 mm = Heaf grade 4 or more => strongly positive.

 POLIOMYELITIS
 Vaccine:
 Organism: Polio virus  Inactivated polio virus = Salk (1956) (IPV)
type I, II, III.
 Live attenuated vaccine = Sabin (1962) (OPV)
 Inactivated at 55 oC for  OPV, eIPV (Enhanced potency Inactivated
30 minutes but this is Polio Vaccine)
inhibited by Mg++, milk,  Contain live strains of virus types I, II, III
ice cream.  Establishes both local gut and blood immunity
 May be given at the same time with other
 Adults more prone to inactivated or live vaccines EXCEPT typhoid.
in-apparent paralytic
infections.
 Efficacy:
 >90% in industrialised countries
 72-98% in hot climates; lower protection against
type III

 Duration of immunity:
Life long if boosted by wild virus, else shorter
DIPHTHERIA:
 Agent: Schick Test:
Toxin producing Corynebacterium  Used to test immunity after
diphtheriae diphtheria immunisation.
 Test solution is the inactivated
 Vaccine = toxoid: toxin.
Comes as liquid + adjuvant  Done at least 3 months after
 Tendency for lower antibody levels immunisation.
in adults due to less natural  No reaction => test -ve =>
boosting. immune subject.
 Erythema lasting approx. 7 days
 Efficacy: > 87% => test +ve => non-immune
 Duration of immunity: subject.
About 5 years. Longer in presence
of natural boosting

 Diphtheria antitoxin:
 IM, IV - to treat suspected cases.
Not for prophylaxis because causes
intense sensitisation.
TETANUS

Agent:
Vaccine =Toxoid

Toxin producing
Clostridium tetani
Children & Adults:
3 doses one month apart:
Reinforce at 10 year
intervals x2 doses is
enough for life.

Booster dose considered

at time of injury.
Rationale for Tetanus Toxoid immunisation
for mothers of child bearing age
PERTUSSIS

Organism:- mainly, Bordetella pertussis

(also B. parapertussis B. bronchoseptica)

Vaccine: - Killed Bordetella pertussis

Caution:
Hx of febrile convulsion: - Advise on prevention
of fever and give.
Hib (HAEMOPHILUS INFLUENZAE type b)

99% typeable strains causing disease are type b.

Diseases:
Meningitis + septicaemia - 60%
Epiglotitis - 15 %
Septicaemia - 10%
Arthritis, osteomyelitis, cellulitis, pneumonia, pericarditis - 15%

Infection rare under 3 months old, rapidly rises in 1st year with peak at 10 -
11 months, then declines till the age of 4 years after which infection is
uncommon.

Vaccine:
Capsular polysaccharide + protein (to enhance immunogenicity in children
less than 1 year old. Capsular polysaccharide alone is not immunogenic in
children less than 18 months).
HEPATITIS B

Double stranded DNA virus (Hepadnavirus)

Carrier rate 2 - 10 %. chronic carriage more frequent in those
infected as children. Higher still for those infected in the perinatal
period.

Among carriers those with HBeAg are most infectious. Those with
anti- HBe are of low infectivity.

A proportion of HBsAg carriers develop chronic hepatitis.

Vaccine:

HBsAg adsorbed onto adjuvant (alum).

HbsAg prepared from recombinant DNA technique from yeast cells.

Notes:

Those older than 40 years are less likely to respond.
“PENTA
PENTA”” Vaccine:
Vaccine:
DPT HepB + Hib

Introduced since 2001

Used in Ghana since March 2002

Supplied as liquid DPT-HepB in one vial and lyophilised Hib in
a separate vial.

Lyophilised Hib can be stored at -20oC or refrigerated at +2
- +8 oC

Liquid DPT-HepB however must not be frozen

Contains preservative. Hence reconstituted vaccine can be
reused over extended period
MMR - Measles Mumps Rubella
Measles, Mumps viruses = Paramyxoviruses (RNA virus)

Measles Vaccine:
◦ Live attenuated
◦ Presentation: Freeze-dried
◦ Route: subcutaneous

Mumps (Parotis epidemica):

◦ Live attenuated vaccine

Rubella = Togavirus
(the only togavirus that is not transmitted by arthropods)
◦ (Single stranded)
◦ Primary purpose of vaccine = to prevent Congenital rubella Infection

Combined vaccine = MMR

YELLOW FEVER
Flavivirus, RNA
Vector - Aedes aegypti

Vaccine:

Live attenuated, freeze-dried containing
17D strain Y. fever virus propagated in
chick embryo.

Contains Neomycin, polymyxin

OTHER VACCINES
TYPHOID

Organism: Commonly, Salmonella typhi, S. paratyphi A, B, C.

Gram negative.

Cause systemic infection but most strains cause local infection in the gut.
All patients excrete organism some time in the stool.
2.5% permanent carriers especially, females.

Vaccines:
1. Heat killed monovalent, phenol preserved
2. Capsular polysaccharide typhoid vaccine (of Vi polysacc of S typhi - not
live)

Single dose leads to 3 years protection

3. Oral vaccine - attenuated S typhi strain TY 21a as enteric coated capsule.

VARICELLA ZOSTER

90% population already infected.

Infection , however, severe in adults, especially pregnant
women.

Zoster = flaring up of dormant varicella.

NB: Congenital varicella syndrome.

Vaccines:
Live attenuated – Single antigen (Varivax)
Combination – With MMR as MMRV (Pro-Quad)
2 doses - 3 mths apart for children 12 mo – 12 yrs
- 1-2 mo apart for children > 12 yrs (NOT MMRV)
 RABIES

Viral zoonosis with carnovires and bats as natural reservoirs

Rhabdovirus, or bullet shaped, single stranded RNA

Vaccines:

Nerve Tissue Vaccines (NTV) – from animal brain tissue
◦ More reactogenic, may cause severe, even fatal, encephalitis, polyneuritis.
Guillian Barre Syndrome reported
◦ Less potent, require a higher number of doses.

Cell Culture Vaccines (CCV) Live attenuated, freeze dried

(human diploid or chick embryo propagated vaccine)

More expensive, Minimal side effects

ID /IM administration. [check insert]
(Days 0, 7, 28. On deltoid. Poor response on gluteal!)

Notes: Chloroquine prophylaxis suppresses Ab response of rabies vaccine

especially if given intradermally.
Rabies -2
Post-exposure treatment
 Factors that should be taken into consideration:
 vaccination status and clinical features of the animal
 type of vaccine used CCV or NTV
 availability of the animal for observation
(in case of use of NTVs)

 less efficient serological response to rabies in Individuals

aged over 50 years.

 Regimen depends on vaccine type

 NTVs currently discouraged but may be in circulation
because it is cheaper
 INFLUENZA
Virus Characteristics:

Orthomyxovirus

Influenza virus types A, B, C1

A & B major; C causes common colds

Influenza A virus spikes:2
◦ haemagglutinins = H1, H2, H3, +
◦ neuraminidases = N1, N2, +

Influenza A viruses also infect animal hosts (e.g. horses,
birds, pigs)3
 Influenza virus nomenclature
Type A virus A/Singapore/6/86

Virus type
Where isolated
H1N1*
Lab code/culture number

Year of isolation

HA subtype

NA subtype

*subtypes for A viruses only

Influenza hospitalisation rates
60
Hospitalisation rate/10,000

50

40
population

30

20

10

0
<5 5–9 10–19 20–34 35–44 45–54 55–64 ≥65
Glezen et al. 1987 Age (yrs)
Influenza virus: antigenic variation

Influenza viruses frequently undergo rapid and
unpredictable changes in their antigenic properties

Vaccines must be updated annually to match circulating
influenza viruses

Antigenic drifts – producing minor variants and caused
by genetic mutations (influenza A and B) [leading to
epidemics]

Antigenic shifts – producing major new strains and
caused by genetic reassortment (influenza A only) [leading
to pandemics]
 20th Century Pandemics
Year Designation Resulting pandemic Death toll

1918 H1N1 Devastating 50-100 million

“Spanish Flu”

1957 H2N2 Moderate 1 million

“Asian Flu”

1968 H3N2 Moderate 1 million

“Hong Kong Flu”

Kamps et al. Chapter 1: Influenza 2006. In Influenza Report 2006. Kamps – Hoffmann – Preiser. Flying Publisher; Kilbourne. Emerg. Infect. Dis.
2006; 12 (1): 9-14; Ghendon Y Eur J Epi, 1994; 10:451-453
 Well-established influenza
Well-
vaccination recommendations

Adults ≥65 years

Individuals with chronic illnesses

Residents of nursing homes and long-term
care facilities

Individuals capable of transmitting infection to
high-risk patients

Children <18 years at risk of Reye’s syndrome

Pregnancy in the 2nd and 3rd trimester

ACIP 2002; Canadian NACI 2001; UK DOH 2002

 New influenza vaccine recommendations

Trend towards a decrease in
minimum age for the elderly:
◦ 50 years in US1
◦ 60 years in Germany, Slovenia
and Iceland

ACIP (Advisory Committee on Immunisation Practices):
◦ influenza vaccination of healthy children aged 6–23 months is
encouraged, when feasible, as they have a substantially
increased risk of influenza-related hospitalisation
◦ a full recommendation to annually vaccinate healthy children
aged 6–23 months could be made within the next 1–3 years

1ACIP 2002
 Current classical influenza vaccines

Whole virion vaccines Split-particle vaccines Subunit vaccines

Furminger 1998
HEPATITIS A

Picorna virus (RNA)

No carrier state, little likelihood of
chronic liver disease.

Hepatitis A vaccine: Formaldehyde
inactivated
NEW VACCINES
FOR EPI
 Pneumococcal Vaccine
Spectrum of Pneumococcal Disease
 Mode of transmission and Carriage
 Direct contact with respiratory secretions from patients and carriers.
 Persons exposed to pneumococci would normally have
transient nasopharygeal colonization (not disease).
 Nearly all children have nasopharygeal carriage of pneumococci
(S. pneumoniae) at one time or the other

Disease:
 Non-Invasive disease: (More common)
 Otitis media
 Sinusitis
 Bronchitis
 Non-bacteraemic pneumonia

 Invasive Pneumococcal disease (IPD):

(i.e. any condition in which S. pneumoniae is present in blood, cerebrospinal fluid or another normally
sterile body site)
 Pneumonia with empyema/and or Bacteraemia, Blood
 Febrile Bacteraemia (CF: 5 – 20%), or
Spread
 Meningitis (CF: 50 – 50%)
Pneumococcal Vaccines-
Vaccines- History
 1977: 14-valent Polysaccharide vaccine licensed

 1983 : 23-valent polysaccharide vaccine(PPV23) licensed

 Pneumococcal polysaccharide vaccine 50 to 60% against invasive disease among

children 24 to 59 months of age (not pneumonia)
 Never been recommended for children < 2yr
(due to poor T cell-independent immune response).
 Recommended for children ≥2 years with underlying medical conditions that
increase the risk for pneumococcal disease e.g. SCD, Asplenia, Chronic renal
disease/ Nephrotic syndrome, Lung disease, Chronic liver disease including
cirrhosis, diabetes mellitus.

 Conflicting result on efficacy testing

 Short-lived immunity
Not associated with induction of immunological memory,
Requiring periodic re-vaccination to maintain protective efficacy.

 2000: 7-valent Pneumococcal Conjugate Vaccine (PCV)

The pathogen
 Gram positive diplococcus

 90+ serotypes based on capsular polysaccharide

 Approximately 20 serotypes account for >70% of invasive disease;

Approximately 10 serotypes commonly associated with pediatric
infections

 Serotypes, antimicrobial resistance profile, and pneumococcal

molecular type (“clone”) are strongly associated

 Variations on global distribution of serotypes varies.

Some serotypes common in developing countries (particularly types
1 and 5) are no longer common in industrialized countries.

 Serotypes associated with invasive infections among HIV infected

children are similar to serotypes that infect healthy children.
 Vaccine Composition of PCV

Vaccine Serotype Composition

7 – Valent 4,6B, 9V, 14, 18C, 19F and 23F conjugated to an
(Prevnar) immunogenic mutant diphtheria (non-toxic)
toxin, CRM197
9-Valent PCV7 + polysaccharide from serotypes 1 and
5.
10-valent 7-valent + 1, 5, 7F

13-valent 10-valent + 3, 6A, 19A

PCV Administration
 Dose: 0.5mls

 Route: Intramuscular

 Recipients: Infants

 Regimen: 3 doses at 4 weeks intervals

 Recommended to start at ≥ 6 weeks,

Hence 6, 10, 14 weeks

 Booster at 12 months improves immune response

 Meningococcal Vaccine
Meningococcal disease
epidemiology:

death-to-case ratio ≥10% in developing
world especially in <1yr olds.

10–20% of survivors develop

permanent sequelae such as epilepsy,
mental retardation or sensori-neural
deafness.

Neisseria meningitidis also responsible
for meningitis occurring beyond the
neonatal and childhood period.

Neisseria meningitidis also responsible
for meningitis occurring beyond the
neonatal and childhood period.

. 4 out of 13 serogroups of N.
meningitidis (N. meningitidis. A, B, C
and W135) recognized to cause
epidemics.

Serogroup A has shown to cause the
epidemics in the meningitis belt,
which extends across Africa from
Senegal to Ethiopia occurring at
intervals of 7-14 years.
MENINGOCOCCUS

Organism: Neisseria meningitidus

Gram negative diplococci, non motile;

Serotypes BCAY W135, Groups A and C usually
associated with epidemics

Carriage rate in normal population 10 - 25%

Short incubation period of 2-3 days.

Vaccine:

Purified, heat stable lyophilised (frozen,
dehydrated) extract of polysaccharide capsule
of N. meningitidus effective against Group A and
C.
Meningococcal Vaccines

Current internationally marketed meningococcal vaccines are based
either on combinations of group-specific capsular polysaccharides (A
and C, or A, C, Y, and W135) or on a conjugate between certain
groups and a protein carrier.

The polysaccharide vaccines are safe and highly immunogenic,

although the group C component is ineffective in children under 2
years of age.

On the other hand, the serogroup C conjugate vaccine is safe and

efficacious even in the youngest children.

(Monovalent polysaccharide vaccines are not readily available)

Vaccines against group B meningococci have shown modest

efficacy in both children and adults
 ROTAVIRUS VACCINES

Rotavirus Infection:
◦ Most common cause of severe diarrhoea in young children

◦ All children infected by age 2-3 years of age

◦ First infections are symptomatic and re-infections are common

◦ Rotavirus strains in circulation

◦ Improvements in water and sanitation will not prevent infection

◦ Way forward  rotavirus vaccines

Clinical Symptoms & Rotavirus
infection
 Primary infection is associated with:
◦ severe dehydration and fever
◦ profuse watery diarrhoea and vomiting
 Associated with >1/3 of all hospitalizations due to
diarrhoeal disease
 Approx 2m hospitalizations globally due to rotavirus
infection
 Associated with high mortality due to the acute &
severe dehydration
 Rotavirus vaccine Immunization
Schedule
(1) Rotarix ®: (GSK lyophilised human G1P8 strain - monovalent)
2 doses; oral live attenuated vaccine
• Children approx 2-4 months
• 1st dose given from 6 weeks but not later than 12 weeks
• Interval between 2 doses  not more than 4 weeks
• 2nd dose by 16 weeks not later than 24 weeks

(2) Rotateq ®: (Human-bovine reassortant, live-attenuated, oral)

(G serotypes - human G1, G2, G3 and G4; bovine G6; human P1A[8] and bovine P7[5])
cross-protective of multiple strains
3 doses; given at 2, 4, 6 months
 1st dose given 6-12 weeks
(don’t initiate vaccination to infants > 12 weeks)
 All doses by 32 weeks

(3) RotaShield® (Wyeth):

License withdrawn
Trails stopped due to increased
incidence of Intususception
 CHOLERA

Organism:Vibrio cholerae; Gram negative curved rod.

Old Vaccine: Heat killed, phenol preserved Inaba, Ogawa, serotypes of V.

cholerae 01. No longer recommended by WHO because of limited
personal protection afforded.

New Oral Cholera Vaccines (OCVs):

Orochol-E®:
Live attenuated single-dose cholera vaccine CVD 103-HgR,
Protective efficacy reached 8 days after administration
Possible use once an outbreak has started

Dukoral®
Killed WC B subunit cholera vaccine (WC/rBS)
Derived from mixtures of WC killed strains.
Given in two doses, 10-14 days apart.
Protective efficacy is reached 10 days after the second dose.
Currently not indicated for use once an outbreak has started.

Neither of the two vaccines protects against Vibrio cholerae O139.
 Human Papilloma Virus Vaccines

Cervical Cancer Prevention

Small, double-stranded DNA viruses that infect the cervical epithelium
 neoplasia.

High risk oncogenic types: 16, 18 causing 70% cervical cancers
 2 vaccines available:
 Quadrivalent Vaccine: HPV types 6, 11, 16, 18
Produced in Yeast
 Bivalent Vaccine: HPV types 16,18
 Ideal age group to vaccinate:10-13 year old girls –not a standard
target population  adolescent vaccination.
 Can be implemented for girls in last year of primary school/first
year of secondary school.
 Catch-up vaccination in older adolescents and adult women?
 Not recommended in a public health programme
 MALARIA VACCINES
P. Falciparum life cycle & potential vaccines

RTS,S
II

III
Transmission through bite of anopheles mosquitoes; Life cycle in two parts;
Asexual occurs in human & Sexual occurs in mosquito (vector).
I – Pre-erythrocytic; II – Blood Stage; III – Transmission blocking vaccines
Features of 3 Malaria vaccine types
Mosquito

Type I-Aborts infection

Type III
before or in liver…no
Blocks transmission
disease…no resulting
blood stage immunity

Blood Type II-Retards infection (and Liver

disease) in blood…enables
development of immunity

Eastern & Southern African EPI Managers Meeting Mombasa, 18-20th March 2009
 RTS,S / AS01 Malaria Vaccine
GSK
No Biologicals/PATH
Biologicals
significant /PATH MVI/BMGF
safety concerns identified to date

Repeats T epitopes S antigen

(from CS protein) (from HBV) RTS & S
co-expressed
in Saccharomyces
RT=Malaria protein + S antigen cerevisiae –
RTS,S VLP

Malaria-Hep BsAg fusion VLP

Proteins are coexpressed
in yeast andVLP
Lyophilised spontaneously
assemble into
Point-of-use particles.
reconstitution with
AS01 adjuvant: liposomes, MPL, QS21

Eastern & Southern African EPI Managers Meeting Mombasa, 18-20th March 2009
 Phase III multi-
multi-centre efficacy trial
MOROCCO
TUNISIA

LIBYA EGYPT
ALGERIA

MAURITANIA
MALI
NIGER
ERITREA
THE CHAD SUDAN
GAMBIA
BURKINA
GUINEA GUINEA
BISSAU BENIN DJIBOUTI
TOGO NIGERIA
COTE GHANA CENTRAL
ETHIOPIA
SIERRA DTVOIRE
LEONE AFRICAN
REPUBLIC
LIBERIA
CAMEROON

UGANDA
EQUATORIAL REP. OF DEMOCRATIC
GUINEA THE REPUBLIC KENYA
CONGO OF THE CONGO
GABON
RWANDA
BURUNDI

TANZANIA

11 participating centres/sites
MALAWI

ANGOLA
ZAMBIA

in 7 African countries NAMIBIA ZIMBABWE

MOZAMBIQUE

BOTSWANA

SWAZILAND
LESOTHO

SOUTH
AFRICA
Eastern & Southern African EPI Managers Meeting Mombasa, 18-20th March 2009
Delayed by one quarter
Stars represent availability of 12 months follow-up data
Malaria Public Health community are in agreement that longer follow-up is necessary
to evaluate possible benefit/lack of rebound. Advisory Group will advise WHO on
this in June 2009

Eastern & Southern African EPI Managers Meeting Mombasa, 18-20th March 2009
VACCINE REACTIONS
Vaccine Reactions

Common, minor reactions
◦ Part of immune response to vaccine,
◦ Generally, Fever, local reactions (pain, redness, swelling), irritability
malaise and non-specific symptoms
Commonly associated with DPT (up to 60% cases)
Symptoms much less common (up to 10%) with all the other EPI
vaccines.
◦ Settle on their own
◦ Warn parents and advise how to manage e.g. fever, malaise etc.

Rare, more severe reactions

◦ Usually require clinical management, e.g., severe allergic reaction
(such as anaphylaxis),Vaccine specific reactions (e.g. BCG osteitis)
 ANAPHYLAXIS

Reported less from developing countries
◦ Less sensitization?, Less reporting?

Anaphylaxis is rare (1/1 000 000 vaccinats)

Fainting is common and untrained staff may
misdiagnose fainting/dizziness for anaphylaxis or vice
versa

Administration of adrenaline during a faint may be
dangerous
PROMPT MANAGEMENT IS VITAL!
ADVERSE EFFECT FOLLOWING IMMUNIZATION
(AEFI
AEFI))
A medical incident that takes place after an immunization, causes
concern, and is believed to be caused by immunization

 Vaccine reaction - caused by vaccine’s inherent

properties
 Programme error - caused by error in vaccine
preparation, handling, or administration
 Coincidental - happens after immunization but not
caused by the vaccine or vaccination process (a chance
association)
 Injection reaction - anxiety about or pain caused by the
injection not vaccine/vaccination
 Unknown - cause cannot be determined
IMMUNISATION SAFETY ISSUES
 Immunisation Safety -1

Vaccine Quality:
Quality of biological process
Character of each batch subject to variation - Hence batch numbers

Diluent Characteristics
Are specific for vaccine in relation to volume, pH, chemical properties

Sensitivity to Heat – Cold Chain
All vaccines are sensitive to heat
BCG, measles, Polio can be kept in freezers
DILUENTS MUST NOT BE FROZEN (e.g. Liquid vaccines containing adjuvants
(aluminium salts) e.g. TT, DPT)
Cool to < 8oC before reconstitution – to prevent vaccine shock from sudden
temperature change
Previously frozen vaccines  reactions and reduced immune response

Sensitivity to light

Shelf life:
Maximum of 2 yrs even under most favourable storage conditions
VACCINE –VIAL MONITOR
Immunisation safety Issues -3
 Multidose vial policy
Previous policy: Discard all opened vaccines vials after immunisation sessions
irrespective of vaccine type and remainder. – NOW OBSOLETE
Current Policy: Mulltidose vials of OPV, DPT (DT) and TT, Hep B
and liquid formulations of Hib vaccines from which one or more
doses have been removed during an immunisation session may be used
in subsequent immunisation sessions for up to 4 weeks
PROVIDED THAT
- Expiry date not expired
- Vaccines stored under approp. cold chain conditions (2 – 8 oC)
- Vaccine vial septum not submerged in water
- Aseptic technique used to withdraw all doses
- VVM if present has not reached discard point
However, for RECONSTITUTED Vaccines e.g. BCG, Measles,Yellow Fever
and some formulations of Hib (Except Pentavalent vaccine), DISCARD
AFTER 6 HOURS OR AFTER IMMUNISATION SESSIONS – which ever
comes first.
 Examples of real safety issues

“Disasters" due to faulty production - Rare;

True vaccine reactions

• Vaccine-associated paralytic polio
• Mumps vaccine-associated aseptic meningitis
• Rotavirus and intussusception
• Bell's palsy following intranasal flu
• Influenza vaccine and oculorespiratory syndrome
Unproven Associations And Public Concern

Influenza vaccine and Guillain Barré Syndrome

MMR and autism, Crohn’s disease

Polio and HIV

Hepatitis B and multiple sclerosis

DTP and permanent brain damage

DTP and increased risk of mortality

Aluminium and macrophagic myofasciitis

Bovine spongiform encephalopathy (BSE)

Thimerosal and autism, neurodevelopmental problems

Multiple vaccines given simultaneously
 Can vaccines overload the
immune system?

Giving multiple vaccines at the same time

is safe

People are exposed daily to hundreds of
antigens

Multiple vaccines work with the immune
system to boost it

Simultaneous vaccination
protects against several diseases quickly

Combo vaccines reduce discomfort and
costs
CONTRAINDICATIONS
True contraindications are rare

Current serious febrile illness: delay vaccine

History of severe reaction after previous dose
(e.g. anaphylactic reaction)

Evolving neurological disease (e.g. uncontrolled epilepsy)
- avoid whole cell pertussis vaccine

No DPT or DPT/HepB/Hib to child with convulsion/shock within 3
days of the most recent dose of DPT or DPT/HepB/Hib.

No DPT or DPT/HepB/Hib to child with recurrent convulsions or
active CNS disease.

Type 1 hypersensitivity to egg - avoid yellow fever & influenza,
can use vaccines made in chick fibroblasts
Contraindications to vaccinations - 2

No live vaccine to:
◦ Pregnant women for risk of teratogenic effect
◦ Patients with malignant disease e.g. leukaemia, Hodgkins disease,
◦ Malignant disease of the RES,
◦ Patients with immune suppression,
◦ Patients on chemotherapy - defer for 6 months after stopping treatment.

Symptomatic HIV
◦ Avoid BCG and YF
◦ Consider withholding measles vaccine in severely IC (monitor immune status)
◦ Measles not recommended if person is seriously ill

Live vaccine virus should not be given within 3 months of giving

immunoglobulin because of inhibition of immune response.
 Immunizing the immunocompromised

Patients may be immunocompromised due

to
◦ HIV , congenital immune deficiencies,
immuno-suppression, e.g. steroids,
chemotherapy, etc., malnutrition

May not respond adequately to vaccination

Risk of disseminated infection from live
attenuated vaccines

In some cases, recommended to weigh risk
of exposure to disease (e.g., BCG in
asymptomatic HIV +ve children)
Important Non-
Non-contraindications to
vaccinations:

 Allergy(except to egg), asthma, allergic rhinitis

 URTI with diarrhoea and mild fever
– temp < 38.5oC
 Prematurity
 Malnutrition
 Family history of convulsions
 Stable neurological conditions e.g. Cerebral palsy, Down
Syndrome
 Treatment with antibiotics, low dose corticosteroids
 History of jaundice after birth
IMMUNISATION FOR PRE-
PRE-TERM INFANTS -1

Theory:

Much of the immune system development occurs

about the 1st and 2nd trimester.

Known deficiencies in new born immune system
appeared to mature as quickly in preterm infant as in
term infant.

Response to antigen in preterms is not significantly
different from term babies (response is related to
exposure and not to gestation. CMI is also
demonstrable in preterms babies).
IMMUNISATION FOR PRE-
PRE-TERM INFANTS
- PRECAUTIONS

 There may be uncertainties about CNS development of the prem

infant, therefore need to weigh the risk of giving against the benefits
or risk of postponing.

 Baby at risk of convulsion may convulse with an immunisation and

so with pertussis vaccine. If you need to suspend pertussis then
postpone the whole DPT (might not get single pertussis vaccine).
IMMUNISATION FOR PRE-
PRE-TERM
INFANTS -3
Recommendations:

 Consider all prems for full immunisation

course.

 Startimmunisation in 2nd month of age (after

4 weeks) irrespective of degree of prematurity.

 Delay OPV in neonatal unit since there is a

small chance of transfer of OPV virus to other
babies. Hence give OPV on discharge from
nursery - not while still on admission.
Notes on vaccine use -1

 All vaccines stored at 2 - 8 oC, not frozen;

Except OPV, eIPV which are stored at 0-4oC.

 Usual dose - 0.5ml IM/deep SC except oral vaccines.

 Except BCG, OPV, other oral vaccines e.g. Salmonella, all

vaccines given either IM or deep SC.
BCG --> intradermal
Rabies, typhoid, cholera, MAY be given intradermally.
Wrong method reduces efficacy
Notes on vaccine use -1
 Interrupted immunisation course  resume, do not
restart. EXCEPT for HIB (use same brand or restart with
different brand)

 No contraindications to the immunisation of the sick child

if he/she is well enough to go home.

 Children with diarrhoea who are due for OPV: give but
don’t count, then repeat after 4 weeks and record this
one as given.

 Don’t give OPV 0 after 15 days

(GHS recommendation: disturbs regular immunisation visits)
Immunizing special populations:
Pregnant women

Safety concerns:
Potential teratogenicity and
induction of abortion, vaccination generally
deferred to 3rd trimester

Vaccinate only if indicated

Live viral vaccines usually not recommended

Birth defect unrelated to the vaccine may be
falsely attributed to the vaccine

Newer vaccines/regimens may have unknown
effects - use with caution

Women (especially adolescents) may not be
aware of or disclose pregnancy , screen?
EPI TARGET DISEASES
Current challenges and strategies to boost EPI

MDG (Millennium Development Goals):

- 4th Goal: Reduce by two thirds the
Mortality Rate among children <5
- 5th Goal: Improve Maternal Health

GIVS (Global Immunization Vision & Strategy):

- Protecting more people
- Introducing new vaccines and technologies
- Integrating immunization in the health systems’
context
- Interdependence

RED (Reaching Every District): reaching “unreached” as an

operational strategy
THE END
 QUIZ

Mother of 7 month old baby weighing 4.5kg presents
with common cold and seeks your professional advise
on further immunisation for the child because he has
received only 2 immunisations since birth.
How will you proceed?

What if baby was born prematurely at 33 weeks?

What if baby’s mother is HIV-positive?