IMMUNISATION Dr.M.L.Siddaraju.

IMMUNISATION Dr.M.L.Siddaraju

DEFINITION Protection from preventable diseases,disabilities and deaths. Birth right of every child Most costeffective healthcare intervention Greek word ‘ímmune’ means ‘ to be protected ’.

Acquired immunity: protection offered by introduction of various antigens or antibodies
The process by which this is obtained is known as immunisation Active immunisation: Specific antigens evoke the needed immune response Passive immunisation:Antibodies are supplied readymade as immunoglobulins and sera.

Some definitions Vaccination: Process of inoculating the vaccine or the antigen Immunisation: Process of inducing immune response, humoral or cell mediated. Seroconversion: Change from antibody negative state to antibody positive state. Seroprotection: The state of protection (from disease) due to presence of humoral immunity or antibody detectable in serum

History Jenner: Cowpox vaccine – 1796
Pasteur: Rabies prophylaxis – 1885 EPI: WHO 1974, India – 1978 UIP: India – 1985 Child vaccine initiative: with support from several international agencies – 1991 Global programme on vaccines: WHO – 1993 Global alliance for vaccine and immunisation

ACHIEVEMENTS Small pox eradicated in 1977
EPI coverage of > 80% by 1990 Certification for polio eradication by 2005 Over 3 million lives saved globally, annually

Types of vaccines Live bacteria- BCG, Ty 21 a Live virus – OPV, MMR
Killed bacteria – Pertussis, S.typhi Killed virus – IPV, Rabies, HAV Toxoid – DT, TT Capsular polysaccharide – HiB, Pneumo, Meningo Viral subunit - HBsAg Bacterial subunit – Acellular pertussis

National Immunisation Schedule
Age Vaccine Birth BCG, OPV – 0 6 wks DPT –1, OPV –1 10 wks DPT – 2, OPV – 2 14wks DPT – 3. OPV – 3 9 months Measles 15-18 months DPT – 4, OPV –4 5 years DT 10 years TT 16 years Pregnant women 2 TT at 4 wks interval

IAP immunisation timetable
Age Vaccine Birth – 2 wks BCG Birth, 6, 10, 14 wks, mo, 5 yrs OPV DPT Birth., 6, 14 wks / 6, 10, 14 wks Hepatitis B Birth, 6, 10, 14 wks, mo HiB Conjugate 9 mo plus Measles 15 months MMR 2 years Typhoid 10., 16 TT / dT Pregnant women 2 doses of TT

Additional vaccines Varicella – above 1 yr Hepatitis A – above 2 yr

Cold chain The system of transporting, distributing and storing vaccines from the manufacturers right up to the point of use under refrigeration using any convenient method is referred to as cold chain Vital link in immunisation If not maintained, vaccine efficacy will grossly suffer Safe temp. zone – mandatory to maintain potency Safe zone for short term storage (1-2 months)is 2-8 deg C. For long term storage –20 degC is used only for BCG,OPV,Measles/MMR The T series of vaccine(DPT,DT,TT),typhoid Vi,Hep B should not be frozen as once frozen the aluminium salts used as adjuvant will be desiccated and will act as irritantsterile abcess

NAME BCG-LAV.Danish bovine strain CONTENT BCG strain of bovine mycobacterium-3-10 million bac/dose PREPARATN Lyophilised INITIATION At birth/first contact SCHEDULE Single dose BOOSTER Nil DOSE 0.05 ml(newborn)0.1 ml(infants and children ADMNSTRN Intra dermal left deltoid EFFICACY 0-80% C/I Immunodeficiency S/E Axillary adenitis

NAME DPT-killed pertusis+toxoid diph&tetanus OPV-LAV CONTENT Diph tox 20 Lf,Tet tox 5 Lf.Pertusis 6 IU(40,000 million killed bacteria +ALPO4-3 mg SABIN, type 1-106(CCID 50),type-2-105(CCID 50),type (CCID50 PREPARATN Liquid INITIATION 6 wks Birth SCHEDULE 3 doses 6,10,14 wks Birth,6,10,14 wks BOOSTER mo,5 yrs DOSE 0.5 ml 2 drops ADMNSTRN I/M lat thigh Oral EFFICACY P80%D80%T100% 80-90% C/I Prog neuro dis,uncontrolled cry,convulsion, severe rxn for 1st dose Immuno defeciency,HIV S/E Fever,local indurn,pain none

NAME Hepatits B(HBsAg) Measles(LAV) CONTENT Plasma derived/yeast derived r-DNA/CHO cells derived r-DNA 1000TCID50.Schwarz or Edmonston Zagreb strain 1000 TCID/CCID PREPARATN Liquid Lyophilised INITIATION Birth w/ I 48 hrs6 wks >9 mo SCHEDULE Birth,6,14 wks/0,1,6 months 1 dose at 9-12 mo.2nd doseafter 3 mo if 1st dose<9 mo BOOSTER Nil DOSE 10 microgram,0.5 ml(<10 yrs), 1 ml(>10 yrs) 0.5 ml ADMNSTRN I/M deltoid S/C deltoid EFFICACY 90% 95% C/I None Imm def,anaphylaxis,egg protein allergy S/E Local pain,erythema Fever ,rash after a week

NAME MMR(LAV) Mumps(LAV) CONTENT Measles as above,Mumps5000 TCID of Urabe AM-9,Rubella 1000 TCID of Wistar RA/3M L-Zagreb/Jerry Lynn strain 5000TCID PREPARATN Lyophilised INITIATION 15 mo 15 mo with M&R or at 11 yrs SCHEDULE Single dose BOOSTER Nil DOSE 0.5ml 0.5 ml ADMNSTRN SC deltoid EFFICACY 95% 90-95% C/I As in measles+pregnancy Imm def S/E As in measles Fever

NAME H Infl b(conjugate) PRPD/PRPT/HBOC TYPHOID(KILLED) CONTENT H.Infl capsular oligosaccharide –b S.typhi 1000 million killed/ml PREPARATN Liquid/freeze dried Liquid INITIATION 6 wks 2 yrs SCHEDULE 6,10,14 wks/2,4,6 mo 2 doses 4 wks apart BOOSTER After 1 yr Every 3 yrs DOSE 0.5 ml.10 mcg 0.25 ml<10yrs,0.5 ml>10 yrs ADMNSTRN SC/IM-deltoid/ant lat thigh SC deltoid EFFICACY 90-100% 57-75% C/I None S/E Local rxn,fever

NAME TYPHOID(Vi polysaccharide TYPHOID oral CONTENT Vi capsular polysach S.typhi Ty 21a strAin(109 organisms) PREPARATN Liquid Capsule INITIATION >2 yrs >6yrs SCHEDULE Single dose 3 doses on alternate days BOOSTER Every 3 yrs DOSE 25-50 mcg(0.5 ml) 1 capsule ADMNSTRN I/M Oral EFFICACY 70% C/I None S/E Fever,pain,induratn Abdominal pain,vomiting, loose stools

NAME Pneumococcal HEP-A (inactivated vaccine) CONTENT Capsular poly saccharide HM 175 of HAV 720 ELU antigen/ml PREPARATN Lyophilised Liquid INITIATION >2 yrs SCHEDULE Single dose 2 doses 0, 6 mo BOOSTER Every 3-5 yrs Nil DOSE 0.5 ml ADMNSTRN SC/IM over Ant. Lat thigh IM antero lat thigh EFFICACY 85-90 % 99% C/I First trimester pregnancy None S/E none Mild reaction

NAME Varicella vaccine Meningococcal A+C CONTENT OKA strain of varicella zoster103(3 PFU) N.meningitidis groupA,C 50 mcg each PREPARATN Lyophilised INITIATION >1 yr For use only in endemic areas during epidemics.>2 yrs SCHEDULE 1-12 yrs(single dose),>13 yrs 2 doses 1 mo apart Single dose BOOSTER Nil 5 yrs DOSE 0.5 ml ADMNSTRN SC deltoid SC/IM-deltoid/Ant lat thigh EFFICACY 95-100% 90-100% C/I None S/E Varicella type rash after 1 wk with fever Local rxn, mild fever

NAME Japanese encephalitis(killed monovalent) Influenza vaccine(inactivated-split virion) CONTENT Mouse brain(Nakayama/NIH strain) or Baby hamster kidney(P-3) or Recombinant DNA vaccine 1.5 mcg hemaglutinin of each of the chosen strain as suspension PREPARATN Freeze dried /liquid Liquid INITIATION Same as meningo cocci All ages SCHEDULE 2 doses 1-2 wks interval Single dose BOOSTER After 3-4 yrs Every year with current strain DOSE 1 ml 0.5 ml ADMNSTRN SC-deltoid/ant lat thigh SC/IM EFFICACY 60-80%,100% after booster 80-90% C/I None Egg protein allergy S/E Local swelling,fever,malaise Local reaction,fever

NAME DPT wc+HB combination DPT wc+Hib CONTENT D and T toxoid+PWC+ yeast derived r-DNA HBsAg D &T toxoid PWC+capsular polysaccharide of Hib PREPARATN Liquid Lyophilised/liquid INITIATION 6 weeks 6 wks SCHEDULE 6,10,14 wks BOOSTER Nil DOSE 0.5 ml ADMNSTRN IM EFFICACY 90-100% C/I Same as DPT None S/E Fever,pain,local induration Mild fever,local induration

NAME Rabies (tissue culture)-inactivated CONTENT HDCV(virus grown in Human Diploid fibroblasts) PCEC (Chick embryo cells) Vero cell(vervet monkey kidney cell) PREPARATN Lyophilised INITIATION Any age-/after dog bite SCHEDULE Pre expo:0.7,21 days.Post expo:0,3,7,14,28.Re expo0,7(<5 yrs), full course(>5 yrs) BOOSTER First after 1 year then every 3 yrs DOSE 0.5 ml/1ml depending on preparatn ADMNSTRN S/C deltoid/ ant lat thigh EFFICACY 90-100% C/I None S/E Local pain,rarely encephalopathy

BCG Vaccine Attenuated M. Bovis developed in 1921
Protects against TB meningitis ,Miliary T B Maternal antibodies do not interfere as CMI not transplacentally transferred Induces long term protection Supplied freeze dried and stored frozen or refrigerated Reconstituted vaccine to be used w/I 4-6 hrs Dose 0.05 ml(infants),0.1 ml(infants and children) Intra-dermal over left deltoid Local lesion due to bacterial multiplication which heals leaving a scar in 12 wks(repeat if no scar) C/I- Immune deficiency Side effect-Axillary adenitis

OPV Live attenuated polio virus types1,2&3-developed by sabin ,1961
Temperature sensitive store frozen or refrigerated Can be given simultaneous with any other vaccine Multiple doses necessary to ensure vaccine virus take and response to all three types of viruses IAP recommends additional doses of opv as a part of pulse polio program every year till age of 5 yrs

Why PULSE POLIO? On national immunisation days(NIDs) pulse doses of oral polio vaccine has to be administered as simultaneous feeding of vaccine to all susceptibles is neede to produce immunity, by preventing wild polio viruses from multiplying in the gut It is mandatory to give all reccomended doses in NIDs so that no wild virus remains in circulation OPV is contraindicated in immunodeficiency,HIV,active viral infections No side effects

IPV Formaldehyde killed polio virus grown in monkey kidney or human diploid cell Contains 20,8,32 D antigen units against type 1,2,3 polio viruses respectively Seroconversion 90-95% after 2 doses,99% after 3 doses Thermo stable and indicated in immunocompromised and HIV

DPT Diphteria toxoid(Ramon &Glenny,1923)
Killed Bordetella pertusis(Madsen ,1923) Tetanus toxoid(Ramon & Zoeller,1927) Toxoids adjuvated (Aluminium hydroxide/ phosphate) Vaccine supplied as liquid, stored refrigerated Aluminium adjuvated vaccine must not be frozen 0.5 ml injected IM on anterolateral asoect of thigh.

Parents must be alerted about local reaction and fever(PCT given)
IAP recommends 2nd booster at 5 yrs H/O convulsion not contradiction Progressive neurological disease or serious adverse reaction to earlier dose are contraindications for DPT(replace with DT)

Measles Live attenuated vaccine developed by Enders-1960
Vaccine further attenuated by Schwarz, Edmonston-Zagreb Supplied freeze dried- store frozen or refrigerated Use reconstituted vaccine in 4-6 hrs(refrigerate do not freeze) 0.5 ml injected S/C preferably right upper arm Age at which recommended 9 months During outbreak>6 months If given < 9 mo repeat dose after 3 mo Possibility of fever for 5-10 days MMR-0.5ml S/C over deltoid(15 mo)

Typhoid WHOLE CELL: Killed S.typhi often with S.paratyphi A(TA)
Developed by Wright ,1896 Liquid,store refrigerated,inject S/C Primary course:2 doses 4 wks apart at 6-9 mo of age or at any age Boosters once in 3-5 yrs Dose : ml S/C for primary,0.1ml for booster

Vi POLSACCHARIDE: Developed by Robbins,1984 Liquid, adjuvated,store refrigerated Inject IM at or after 2 yrs of age(0.5 ml) Booster after 3 yrs

ORAL: Live attenuated S.typhi developed by Germanier,1975 Strain name:Ty 21a Enteric coated capsules,store refrigerated, administer orally 3 doses on alternate days Repeat 3-5 yrs later Recommende age7 yrs or above

Hib vaccine H . Influenza B-capsular polysaccharide
Liquid or freeze dried Age of initiation 6 wks 3 doses 6,10,14 wks/2,4,6 mo Booster 1 yr after primary dose Dose 0.5 ml SC/IM over deltoid or anterolateral aspect of thigh

ADDITIONAL VACCINES Varicella vaccine:
Developed by Takahashi in 1971,Japan Live attenuated Oka strain. Vaccine available as lyophilized powder Dissolve in 0.5 ml diluent SC 0.5 ml Single dose 1-12 yrs >13 yrs 2 doses at 1 mo interval

Hepatitis A Inactivated vaccine containing H M 175 strain grown in MRC5 cell line. Pediatric formulation 720 ELU IM; 2 doses 6 mo apart between 2-18 yrs >19 yrs 1440 ELU 2 doses 6 months apart Efficacy % No boosters

Vaccines recommended during epidemics
Japanese B Encephalitis vaccine Meningococcal A&C

Vaccines for high risk group
PNEUMOCOCCAL VACCINE: Polysaccharide vaccine(23 valent) 7 Valent conjugated with CRM 197 diphtheria toxin 23 valent effective after 2 yrs of age Single dose 0.5 ml IM with booster every 3-5 yrs

Indications Sickle cell disease Nephrotic syndrome in remission
Congenital or acquired asplenia/splenic dys function HIV Chronic cardiac/pulmonary disease Immunodeficient conditions CSF leak Diabetes mellitus

Combination vaccines DPT/HiB/HepB Benefits:
1. Reduced number of injections 2. Reduced pain and parental anxiety 3. High compliance, low drop out rates,enhanced coverage 4. Reduced no: of visits 5. Less storage space 6. Less burden on cold chain

Vaccination schedule for unimmunised child
<5 yrs >5 yrs First visit BCG,OPV,DPT,HB TT/Td,HB 2ND visit(1 mo later) OPV,DPT,HB 3RD visit(1 mo later) OPV,DPT,MMR/Measles,Typh MMR,Typh 1 yr later HB Every 3 yrs Typh booster

Newer vaccines Live attenuated varicella(oka)strain
Killed hep A virus vaccine 23 valent pneumococcal vaccine Influenza virus vaccine Combination vaccines

Vaccines available in other countries
Conjugated pneumococcal vaccine(7 valent) Conjugated S.typhi Vi vaccine Rota virus vaccine Combination vaccines

ADVERSE EFFECTS

ADVERSE EVENT VACCINE SYMPTOMS MANAGEMENT Anaphylaxis any W/I minutes,acute decompensation of circ. System,hypovolemic shock,laryngeal spasm/edema.Acute respiratory distress Adrenaline,CPR,IV volume expanders or dopamine/dobutamine, hydrocortisone Hypotensive,hyporesponsive episodes DPT Within 12 hrs.Acute paleness.Transient decreased levels/loss of consciousness.Dec muscle tone IV fluids, dexamethasone,oxygen

Within 48-72 hrs.Excessive inconsolable crying
ADVERSE EVENT VACCINE SYMPTOMS MANAGEMENT Incessant cry DPT Within hrs.Excessive inconsolable crying Sedation with triclofos-50mg/kg/day+PCT+feeding advice Toxic shock syndrome Measles contamination by S. Aureus Within 30 min- few hrs. Mounting fever,vomiting, diarrhoea,septic shock IV fluids,anti microbials,cloxacillin mg/kg/day, steroids,antipyretics,supportive therapy

Within 72 hrs,fluctuant or firm abcess with or without fever
ADVERSE EVENT VACCINE SYMPTOMS MANAGEMENT lymphadenitis BCG Within 2-6 months firm-soft axillary lmphadenitis1.5-3 cm with/ without sinus If firm no treatment.If soft&fluctuant HR3.Aspiration if needed.Steroid if sinus present Bacterial abcess Any vaccine Within 72 hrs,fluctuant or firm abcess with or without fever Antibiotics, Anti pyretics,drainage if needed

By 72 hrs ,minimum inflamation, no fever Drainage if needed
ADVERSE EVENT VACCINE SYMPTOMS MANAGEMENT Sterile abcess DPT,DT,TT,Typhoid & HEP B By 72 hrs ,minimum inflamation, no fever Drainage if needed Moderate to severe local reaction Any vaccine Non fluctuant swelling/redness 3-10 cm in size at injection site Paracetamol

Seizures with fever(rare) Always generalised simple/complex
ADVERSE EVENT VACCINE SYMPTOMS MANAGEMENT Seizures with fever(rare) DPT, measles Always generalised simple/complex Anticonvulsant,antipyretic,IV fluids (if needed)

IAP recommendations on Immunisation,2003
The IAPCOI-Indian Academy of Pediatrics Committee On Immunisation,has formulated several scientific recommendations to other agencies pertaining to Immunisation

Recommendation to federation of OBG societies of India
To adopt routine testing of all pregnant women for HBV infection and if mother is positive baby should be given HBIG+HB vaccine soon after birth

Recommendations to Ministry of Health, Govt of India
The academy should be represented on National Technical Advisory Group on Immunisation At 5 yrs booster immunisation with DPT rather than DT. Inactivated polio vaccine should be licensed and gradually introduced in phased manner Hep B and MMR vaccine should be included in national immunisation schedule immediately Govt. should consider inclusion of typhoid vaccine(Vi polysaccharide/whole cell inactivated) in the national immunisation schedule Another vaccine to be included is Hib Ensuring adequate supply of chick embryo/ tissue culture rabies vaccine

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