IMMUNIZAION

06/22/2024 1
 OUTLINE

 Introduction
 Goal of vaccine
 Definitions
 Vaccine types
 Expanded Program for Immunization (EPI)
 Specific vaccines
 Cold chain
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 INTRODUCTION

 Immunization is remarkably successful and very cost effective means of communi-

cable disease control

 More than 50 immunobiologic products are available for clinical use

 Sustainable financial support, well-organized infrastructure and epidemiology of

disease will determine the type of vaccine used in given country

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 GOAL

 Immediate:
 To prevent disease in individuals
 Ultimate:
 To eradicate a communicable disease

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 DEFINITIONS

 Immunization:
 A process of inducing immunity artificially by either vaccination(Active) or ad-
ministration of antibodies(Passive)

 Vaccination:
 Administration of any vaccine or toxoid for prevention of disease

 Immunity:
 The ability of the body to recognize and destroy foreign antigenic material like
bacteria, viruses or their toxic products leading to resistance to infection
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06/22/2024 6
 Active Immunization (Vaccination)

 Is an antigen, when administered stimulates specific antibody formation

with resulting immunity against the particular disease
 It is prepared from:
 Live attenuated organism
 Killed organism
 Toxoid
 Genetic engineered

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 Live Attenuated Vaccines

 Attenuated form of the "wild type" virus or bacteria

 Must replicate to be effective

 Immune response similar to natural infection

 Usually effective with one dose

 Usually mild but severe reactions are possible (7-21 days)

 Interference from circulating antibody

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 Live Attenuated Vaccines…

Viral:
 Influenza (intranasal) Bacterial:
 Measles  BCG
 Mumps
 Oral typhoid
 Polio (oral)
 Rotavirus
 Rubella
 Varicella
 Yellow fever

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 Inactivated Vaccines

 Cannot replicate

 Minimal interference from circulating antibody

 Generally not as effective as live vaccines

 Generally require 3-5 doses

 Immune response mostly humoral

 Antibody titer diminishes with time

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 Inactivated Vaccines…

 Whole virus:
 Polio (IVP), Hepatitis A
 Whole bacteria:
 Pertussis, Cholera, Typhoid
 Protein-based subunit:
 Hepatitis B, Influenza, acellular Pertussis
 Toxoid:
 Diphtheria, Tetanus
 Polysaccharide-based:
 Pure: Pneumococcal, Meningococcal
 Conjugate: Pneumococcal, Hib, Meningococcal

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 Determinants Of The Immune Response

 Nature of vaccine
 Potency
 Route of administration
 Host factors:
 Age
 Nutrition
 Preexisting antibodies
 Genetic

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 Expanded Program of Immunization (EPI)/WHO

 Started in 1974
 Aims to provide free immunization
 Main purpose:
 Prevent childhood diseases
 Provide high quality vaccines
 Surveillance of these diseases
 Schedule of immunization is designed according to epidemiological terms of dis-
eases together with sociocultural & economic factors

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 Vaccine preventable diseases, currently having vaccine, WHO
 Recommendations for all immunization  Recommendations for certain regions
programmes  Japanese Encephalitis
 Tuberculosis  Yellow Fever
 Poliovirus  Tick-Borne Encephalitis
 Recommendations for some high-risk popula-
 Hepatitis B virus
tions
 Hib  Typhoid
 Diphtheria  Cholera
 Tetanus  Meningococcal
 Pertussis  Hepatitis A
 Pneumococcal pneumonia  Rabies
 Rotavirus  Dengue
 Measles  Malaria
 Recommendations for immunization pro-
 HPV
grammes with certain characteristics
 Rubella  Mumps
 Seasonal influenza
 Varicella
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 EPI In Ethiopia

 1980- launched targeting 6 diseases (BCG, OPV, DPT and Measles)

 2007- Hep-B and Hib (added to DPT and become Pentavalent vaccine)
 2011- PCV
 2013- Rotavirus vaccine (RVV)
 2015- IPV
 2018- HPVV
 2019- Measles second dose (MCV2)
 2020- Td for women of reproductive age group
 Next plan- Hepatitis B birth dose, Meningitis A, Yellow Fever, Typhoid
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 EPI In Ethiopia…

 Current Ethiopian national routine immunization includes:

 One dose of BCG
 Three doses of dpt-hepb-hib (pentavalent)
 Three doses of pneumococcal conjugate vaccine (PCV)
 Two doses of rotavirus vaccine (RVV)
 Four doses of OPV
 One dose of IPV
 Two doses of measles (MCV)
 Two dose of HPV with at least six month interval for 9-14 years old girls
 Five doses of Td for women child bearing age group (15-49 years)

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 EPI Schedule In Ethiopia
Age Vaccine Route/Site Dose

Birth BCG/OPV0 ID, right deltoid/PO 0.05ml/2drops

6wks Pentavalent1/PCV1/OPV1/Rota1 IM, Lt thigh/IM, Rt thigh/PO 0.5ml/2drops/1ml

10wks Pentavalent2/PCV2/OPV2/Rota2 IM, Lt thigh/IM, Rt thigh/PO 0.5ml/2drops/1ml

14wks Pentavalent3/PCV3/IPV/OPV3 IM, Lt thigh/IM, Rt thigh/ IM, Rt 0.5ml/2drops

thigh/PO

9month MCV1 SC, left deltoid 0.5ml

15month MCV2 SC, left deltoid 0.5ml

14yrs, girl HPVV (2doses) IM, left deltoid muscle of upper arm 0.5ml

15-49yrs, Td (5doses) IM, right deltoid Muscle 0.5ml

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women
 EPI…

 Premature babies are vaccinated like other babies b/c response to antigens is de-
pendent on postnatal age
 Minimum interval b/n each schedule is 4weeks, however, there is no maximum in-
terval between the doses as long as it is given before the age of one year except for
measles and HPV
 Longer than recommended intervals between doses do not reduce final antibody con-
centration
 If a vaccine is given before 4wks of the previous dose, it shouldn’t be counted as part
of the series
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 EPI…

 All EPI antigens are safe & effective if administered simultaneously (give at differ-
ent sites on the same day)
 Maternal antibodies transferred through the placenta protect the infant up to 3-
4months and if vaccine is given before 1month of age, circulating antibodies may
neutralize the antigens
 Practically there are no major contraindication for vaccination
 Live vaccines shouldn't be given to severely immunocompromised children

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 EPI…

 The child should be considered as fully immunized if he/she received all vaccines
including MCV1 before first birth date
 However, the certification of completion of routine immunization should be issued
to the caretaker or child when she/he received MCV2 during the 2nd year of life
 Additional “booster” doses are not recommended except for diseases targeted for
elimination and eradication
 Deep injection and massage may reduce antigenic efficacy

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 BCG (Bacillus Calmettie Guerin)

 The only available vaccine against tuberculosis

 Live attenuated M. bovis
 Sensitive to heat and light
 No antibody interference with BCG, b/c protection of TB depends on cell-mediated
immunity so that BCG can be given at birth
 BCG can be given for children less than five year old, if not received at birth
 Protection is lost with age
 From as early as age 5 years, no significant protective effect can be observed

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 BCG…

 No BCG for AIDS patient but can be given for sero positive children
 Prevent life-threatening forms of TB in infants and young children
 Little effect on preventing transmission

 Efficacy:
 50-80% for severe form of the disease (disseminated and meningeal TB)
 0-80% for pulmonary TB

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 Side Effect (BCG)

 Kochs phenomenon– self limiting acute inflammatory reaction four days after vaccina-
tion
 Indolent ulcer– ulcer persisting 12 wk after vaccination or ulcer more than 10mm,
mainly resulting from deep injection or secondary infection
 Deep abscess– abscess at site of injection or draining lymph nodes due to subcutaneous
or deep injections
 Disseminated disease with BCG – one per million vaccines results in active disease es-
pecially in immunosuppressed children

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 BCG…

 The scar after BCG vaccine has two uses:

 Witnesses the child is vaccinated
 Good degree of immune response

 N.B- Absence of BCG scar should not be a condition to provide addi-

tional dose of BCG vaccine to a child

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 Oral Polio Virus (OPV)

 Trivalent OPV (t-OPV) was switched to bivalent OPV (b-OPV) in 2016

 Bivalent (combination of type1& 3) is recommended by WHO for routine infant im-
munization
 For all countries using OPV in their national immunization programme, WHO rec-
ommends 3 doses of bOPV and 1 dose of IPV (OPV1 should start from 6weeks)
 In countries at high risk, WHO recommends a bOPV birth dose (zero dose) followed
by the primary series of 3 bOPV doses and 1 IPV dose
 Birth dose OPV (OPV0) means vaccine given within fourteen days of delivery

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 OPV…

 Advantage of OPV0:
 To maximize seroconversion rates following subsequent doses
 To induce mucosal protection before enteric pathogens may interfere with the
immune response
 Prevent VAPP, maternally derived antibodies effective at this time
 The immunogenicity is less affected by maternal antibodies

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 OPV…

 Live attenuated
 Damaged by heat but not by freeze
 It produce life long local intestinal & systemic immunity (IgA)

 Efficacy is >90%
 Side effect:
 Doesn't’t have common side effect
 Rarely paralytic poliomyelitis (VAPP) has been reported

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 Inactivated polio vaccine (IPV)
 Trivalent inactivated polio vaccine ( contain all thee types)
 Elicits higher serum IgG antibody titers
 It does not replace b-OPV doses
 It will continue to be provided side by side with b-OPV
 Provide immunity against paralysis from type 2 poliovirus and also boost immunity
against poliovirus types 1 and 3
 IPV alone does not induce the same level of intestinal immunity as OPV
 An IPV-only schedule may be considered in countries in polio-free regions
 Has no adverse effects
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 Pentavalent Vaccine

 The Pentavalent vaccine combines five different vaccines in one injec-

tion to protect against:
 Diphtheria
 Pertussis
 Tetanus
 Hepatitis-B virus (HBV)
 Haemophilus influenzae type B (Hib) disease

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 Tetanus Toxoid (TT)

 It is inactivated by heat and freeze

 If the person has previously suffering from the disease, he should be vaccinated
 Booster injection should be given every 5-10yrs

 Side effect :
 Arthus reactions (type III hypersensitivity reactions) which is rare

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 TTCV

 DT
 DTaP (Daptacel and Infanrix)
 DT/DTaP:
 Td (Tdvax and Tenivac)
 Tdap (Adacel and Boostrix)  For children (<7yrs)

 DTaP-HepB-Hib (Pentavalent)  Td/Tdap:

 DTaP-HepB-IPV (Pediarix)  For adolescent & adults
 DTaP-IPV/Hib (Pentacel)
 DTaP-IPV (Kinrix and Quadracel)
 DTaP-IPV-Hib-HepB (Vaxelis)
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 TTCV…

 The WHO-recommended six doses vaccine schedule for TTCV

 A three-dose primary infant series and three booster doses:

 DTaP- At ages of 2, 4 & 6 moths (primary series)= +3 years protection

 DTaP- At ages of 12–23 months (1st booster) = +5 years protection

 DTaP- At age of 4–7 years (2nd booster) = +10 years protection

 Tdap- At age of 9–15 years (3rd booster )= Fully protected

 Efficacy:- >80% after 2 doses, >95% after 3 doses, >99% after 4 & 5 doses

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 Diphtheria Toxoid

 May not prevent respiratory or cutaneous infection

 Decreases local tissue spread
 Prevents toxic complications (Cardiac & CNS)
 Diminishes transmission of the organism
 Provides herd immunity
 Damaged by freezing and heat
 Efficacy:- >80%
 Duration of immunity: variable, probably around 5 yrs

 S/E :- no significant adverse reaction have been associated

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 Pertussis Vaccine

 It is killed B. pertusis
 DTaP- licensed for children <7 year old
 Tdap (reduced form)- for adolescents (11-12 yr) & Pregnant women
 Sensitive to heat
 Efficacy:- variable, around 80% for severe disease
 Duration of immunity:- unknown

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 Side Effect (Pertussis Vaccine)

 Fever (high grade)

 Local soreness (3-4days)
 An abscess at the site of injection
 Febrile seizure (0.3-9/100,000dose)
 Permanent brain damage
 Encephalitis (0.3-0.6/100,000dose)
 Shock like state are common >6months age

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 Contraindications (Pertussis Vaccine)

 Convulsion with in 3 days following vaccine

 Shock like state

 High grade fever (400c)

 Progressive neurologic deficit

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 Hepatitis B vaccine

 It is inactivated product produced by genetic engineering

 Can be monovalent (Recombivax and Engerix) or combination (Pentavalent, Pedi-
arix and Twinrix)
 Three doses needed if the monovalent vaccine is used as series vaccine schedule, ex-
cept for birth weight <2000gm infant exposed to HBsAg positive mother or unknown
status, needs 4th dose
 Administration of 4 doses of vaccine is permissible when combination vaccines are
used after monovalent vaccine birth dose

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 Hep B vaccine…

 Seropositivity is >95% with all vaccines after the second dose in most patients
 The safety profile of Hep B vaccine is excellent
 Side effect:
 No major side effect
 Pain at the injection site
 Fever

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 Hep B vaccine…

 For HBsAg positive mother:

 The newborn should receive hepatitis B vaccine & hepatitis B immunoglobulin
(HBIG) within 12hr of delivery at different site
 There is evidence to suggest that HBIG alone, Hep B vaccine alone and HBIG
plus Hep B vaccine given at birth prevents hepatitis B occurrence in the newborn
exposed to HBsAg positive mother
 Then follow the routine vaccination schedule from six weeks
 Check HBsAg for infant at 9month

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 Hep B vaccine

 For unknown HepBsAg status mother:

 The newborn should receive hepatitis B vaccine at birth
 Mother should be tested for hepatitis B serology and if HBsAg positive, the infant
should also receive HBIG within 48 hours (up to 7days acceptable)
 Follow the routine vaccination schedule from six weeks

 For HBsAg negative mother:

 Follow the routine vaccination schedule from six weeks

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 Hep B vaccine

 Post vaccination testing for HBsAg and anti-HBs should be done at 9 mo:
 If HBsAg is negative and anti-HBs level is >10 IU/L , immunity is proven
 If HBsAg is positive, the baby has become infected despite prophylaxis & baby needs
evaluation by pediatric hepatologist
 If HBsAg is negative and anti-HBs level is ≤10 IU/L, give one to three further doses of
HBV at least four weeks apart
o Recheck serology four weeks after each dose to determine if further doses are
necessary (i.e., if anti-HBs is still ≤10 IU/L)
o If there is no seroconversion after the third dose of HBV, need further evaluation
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 Haemophylus Influenzae Type B vaccine

 It consists of a capsular polysaccharide conjugated to a protein

 It stimulate circulating anticapsular antibody
 Provide long-term immunity through B-cell memory
 More than 95% reduction of Haemophilus Influenza type B disease
 Immunization should start from 6 weeks of age
 Hib vaccine is not required for healthy children after 5 years of age
 Keep it at +20C -+80C, don’t freeze

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 Pneumococcal Conjugate Vaccine (PCV)

 More than 102 pneumococcal serotype have been identified so far

 It is not possible to include all serotypes in pneumococcal vaccine
 The serotypes most frequently isolated and invasive disease are included in the avail-
able vaccines
 PCVs that include 7, 10, 13, 15, 20 & 23 have been developed
 Currently PCV13 is recommended for all infants on a schedule for primary immuniza-
tion

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 PCV…

 Highly immunogenic in infants and young children

 Induce a T-cell dependent immune response
 >90% effective against invasive disease
 Less effective against pneumonia and acute otitis media
 WHO does not currently have recommendations on the use of PCV in individuals over
5 years of age
 May reduce pneumococcal transmission through a herd effect

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 PCV7 (Prevnar)

 Serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F

 Carrier protein: Diphtheria CRM197 protein

 Reduce invasive disease caused by vaccine serotypes by 97%

 Reduce invasive disease caused by all serotypes, including vaccine serotypes by 89%

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 PCV13 (Prevnar13)

 Serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F

 Carrier protein: Diphtheria CRM197 protein

 Is recommended for all infants on a schedule for primary immunization

 Significant reduction in IPIs caused by vaccine serotypes

 Reduce rates of hospitalization after PCV13 introduction

 Significantly reduce nasopharyngeal carriage of vaccine serotypes

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 PPSV23 (Pneumovax II)
 Serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A,
19F, 20, 22F, 23F, 33F
 Pneumococcal polysaccharide vaccines
 No carrier protein
 Reduce >95% of invasive disease
 Less effective in preventing pneumococcal pneumonia
 Not effective in children less than 2 years
 No effect on nasal carriage
 No herd effect
 Absence of immunologic memory
 Antibody level to decline to pre-vaccination values within 3-7 years

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 PCV Adverse Reactions

 Local reactions
 polysaccharide 30%-50%
 conjugate 10%-20%

 Fever, myalgias
 polysaccharide <1%
 conjugate 15%-24%

 Severe adverse reactions rare

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 Rota Vaccine (RV)

 Rotashield, a trivalent rotavirus vaccine implemented in 1998

 Rotashield withdrawn within one year because of association with intussusception
 1 intussusception per 10,000 vaccinated infants
 Later two new live, oral rotavirus vaccines have been approved:
 Monovalent (Rotarix)
 Pentavalen (RotaTeq)
 Not recommended for children >24 months of age
 Vaccination may be postponed in case of ongoing acute gastroenteritis
 Contra indication- Severe immunodeficiency
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 Licensed Rota Vaccine

Rotarix® RotaTeq®
Route oral oral
Efficacy >85% for severe 90-100% for severe
74-85% any severity 74-85% any severity
Antigen Monovalent Pentavalent

Schedule 2 doses 3 doses

Protection against 2 years 2 years

severe infection

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 Measles Vaccine (MCV)

 Live attenuated measles virus

 Damaged by heat
 Maternal antibodies against measles persist unto 9-12 months of age
 If given earlier the maternal antibody will damage the vaccine
 In countries with high transmission & mortality rate, MCV1 should be given at age
9months & MCV2 should be given between 15-18months
 In countries with low transmission rate (i.e. those that are near elimination or veri-
fied as having eliminated), MCV can be given at 12-15mo and 4-6yr of age
 Minimum interval between MCV1 and MCV2 will be one month
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 MCV…

 During measles outbreak, some recommend the vaccine at the age of 6 month
 If infants received a dose before 9mo of age, record as MCV0 & two additional
doses (MCV1 & MCV2) should be given according to national EPI schedule
 Seroconversion is slightly lower in children who receive the 1st dose before or at
12month of age because of persisting maternal antibody
 87% at 9 month, 95% at 12 month, and 98% at 15 month
 Has lifelong protection

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 MCV…
 After measles exposure:
 Give measles vaccine within 72hrs
 Give IgG within 6days (for <6mo, immunocompromised, pregnant mother)
 After measles infection:
 It induce life long immunity (has lifelong protection), immunization is not needed

 Tuberculosis:
 Immunize; if patient has untreated TB, start antituberculosis therapy before immu-
nizing

 HIV infected:
 Immunize, unless severely immunocompromised

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 Side Effect (MCV)

 Fever (after 1wk)

 A mild measles like rash self limited
 Major side effects (per 100,000 vaccinations):
 Encephalopathy (0.1)
 Convulsions (0.02 – 100)
 Sub acute sclerosing panencephalitis (0.01 – 0.05)

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 Catch - Up Immunizations

 Refers to the action of vaccinating an individual, who for whatever reason (e.g. de-

lays, stock outs, access, hesitancy, service interruptions, etc.), is not vaccined for

which they are eligible, per the national immunization schedule

 All routine vaccine antigens are eligible for catch-up except Hep B birth dose, HPV

vaccination and Td vaccination

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 National Catch - Up Immunizations Schedule
Vaccine Total Minimum age Minimum interval between doses Upper age limit
antigens doses for dose 1
BCG 1 At birth NA Up to 1 year of
age
OPV 4 At birth OPV0-OPV1: 6 weeks, All subse- Up to 59 months
quent doses: 4 weeks
Rota 2 6weeks 4weeks Up to 24 months
PCV 3 6weeks 4weeks Up to 24 months
Penta 3 6weeks 4weeks Up to 24 months
IPV 2 14weeks 4weeks Up to 24 months
Measles 2 9months 2nd dose at 15 months; Minimum 4 Up to 59 months
weeks between dose 1 and 2 if
dose 1 is given late

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 Other Methods Of Immunization

Outreach Immunization

Mobile Immunization

Mass Immunization

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 Cold Chain

 A network of refrigerators, cold stores, freezers and cold boxes organized and main-
tained so that vaccines are kept at the right temperature to remain potent during orders,
supplies, transportation, storage, distribution to the point of administration to the target
population
 Monitor and record the temperature of the vaccines in the cold chain at least twice daily
 Opened vials of measles, BCG, PCV13, yellow fever and meningococcal vaccines must
be discarded 6 hours after reconstitution

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 Cold Chain…

Type of vaccine Storage temperature

Most sensitive to heat OPV -150c to – 250c

MCV -150c to – 250c

Least sensitive to heat Pentavalent 2 0c to 80c

BCG 2 0c to 80c

TT 2 0c to 80c

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 References

1. Nelson Text Book Of Pediatrics, 21st Edition

2. Ethiopia National Expanded Programme On Immunization, 2022
3. WHO Immunization Updates, 2023
4. National Implementation Guideline For Expanded Program On Immunization, Re-
vised Edition, 2021
5. Routine Catch-up Vaccination, MOH-Ethiopia, 2022

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 Thank you!

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