RECENT ADVANCEMENT IN IMMUNIZATION

GOALS OF IMMUNIZATION

• IMMEDIATE :prevention of disease in individuals

• ULMITIMATE : eradication/ elimination of disease from the world

EFFECTS OF IMMUNIZATION( US BASED DATA )

DISEASE SMALL POX POLIO PARALYTIC

MEASELS HAEM.INFLUENZA TYPE B

MORBIDITY 20TH CENTURY

48164 16311 503282 20000

MORBIDITY 2007

ZERO ZERO 43 22

% DECREASE 100 100 >99 >99%

PARENTS CONCERNS ABOUT IMMUNIZATION

• Safety of immunization• Objections due to religious thoughts• Past experience or hear say• Disease would give better protection than vaccine• Combine vaccines given on one visit may have more side

effects• Cost. • They should be counselled in detail, referred to different

literatures and websites like www.aapnews.org / www.immunizationfo.org

Types of immunization1. Active immunization2. Passive immunization

ACTIVE IMMUNIZATION: 1. The administration of all, part of micro

organism ,modified product of that organism , resulting in an immunologic response that mimics that of the natural disease but usually present no or little risk for the recipient

It may provide life long protection ,partial protection or may require administration at regular intervals.

PASSIVE IMMUNIZATION

• It is the administration of preformed antibodies to recipients

• It is available as• immunoglobulin, I/M• specific immunoglobulins ,• Immunoglobulin I/V• Indications are immunodeficiency states, ITP, Rabies

(rabies Ig) Tetanus(TIG), tetanus antitoxin, Diptheria anti toxin

VACCINE HANDLING AND STORAGE

• Transported/stored at recommended temperature

• Live virus attenuated vaccine are heat sensitive and destroyed at high temperature e.g MMR Rota Virus OPV etc

• Inactivated vaccine are cold sensitive but they are destroyed by freezing e.g DPT, IPV, HiB, Hep A & B etc

SCHEDULING IMMUNIZATION

• Two programmes are available in our country

• Expanded Programme for immunization (EPI)

• Programme recommended by American Academy of Pediatrics (AIP)

GUIDLINES FOR MAJOR VACCINES• BCG• Prepared from live attenuated M. Bovis • Method of administration• Natural course of BCG vaccine• Accelerated BCG response • Evidence of successful BCG vaccine• Protective efficacy• Adverse reaction like abscesses disseminated fatal

disease, axillary adenitis etc• Contraindiactions include burns, skin infections,

primary and secondary immunodeficiencies

POLIO• Two types • 1)inactivated polio virus IPV given parentally I/M or

S/C• 2)live virus vaccine given orally OPV • OPV is easy to administer low cost and more

effective immunization• Both vaccines contain 1,2&3 polio strains • Two doses of IPV results in 95% and 3 doses results in

99-100% immunity probably life long• Three doses of OPV gives excellent antibody

response

• Adverse Effects of IPV• No serious side effect except the

hypersensitivity to neomycin streptomycin and polymyxin and can be given to immunocompromised persons

• Adverse Effects of OPV• OPV associated VAPP =1:750000 doses• Overall risk for VAPP =1:2.4 million doses

DIPTHERIA TETANUS AND PERTUSSIS IMMUNIZATION

• DwPT and DaPT• Contains • 1)Diptheria Toxoids • 2 )Pertussis(killed whole cell/Acellular) and• 3)Tetanus Toxoid • Schedule : 5 doses at 2, 4, 6, 15-18 months

and 4-6 years of age, over 7 years child should receive Tdap

TETANUS • 5 doses as mentioned above in the form of

DTwP, DtaP, DT, Tdap • Wound management

H/o Tetanus Toxoid (doses) Clean wound Td/Tdap TIG

All other wounds Td/Tdap TIG

Less than 3 or unknown Yes No Yes Yes

More than 3 No No No No

Tetanus prophylaxis

• TIG 250 units I/M regardless of age and weight• IVIG can be used if TIG is not available• ATS (equine Antitoxin Serum) is better avoided

because of anaphylaxis and serum sickness• Tetanus immunization with Tetanus Toxoids

can be initiated simultaneously

Prevention of neonatal tetanus (prenatal immunization)

• Pregnant women who have not completed their primary series (3 doses) should do so preferably before delivery

• 2 doses of Td 4 weeks apart 2nd being given 2 weeks before delivery

• Immunization with TdaP/Td is not contraindicated during pregnancy

• Adverse reaction with Tetanus Toxoids include Anaphylaxis, GBS, Brachial neuritis but are rare

PERTUSSIS

• 5 Doses as mentioned earlier• DwPT contains whole cell killed Pertussis

organism and is immunogenic as well as reactogenic

• Acellular pertussis contains two or more immunogens derived from B-Pertussis

Side effects Whole cell vaccine Acellular vaccine

Local reaction more Much less

Systemic More Much less

Anaphylaxis 2 per million Much lessSeizures 1:1750 doses Much less

HHE 1:1750 Much less

Temp 105F In 0.3% reciepients Much less

crying for more than 3 hrs 1% Much less

CONTRAINDICTIONS FOR DTaP

• Anaphylactic reaction • Encephalopathy with in 7 days after receipt

of Dtap• Progressive neurological disorder

HEPATITIS B VACCINE

• HBV is produced by Recombinant DNA technology• 3 doses of HBV (Engerix-B)10 microgram I/M 0,1

and 6 months upto age of 20 years .Over 20 years 20 microgram I/M is needed

• 4 doses of HBV may be administered at birth. If birth dose is given and a combination of vaccine is used to complete the series

• Efficacy and duration of protection is 90-95% and immune memory is intact for 20 years

INDICATION FOR BOOSTER DOSES OF HBV

• Patients on hemodialysis• Immunocompromised• Health workers

MANAGEMENT OF NON RESPONDERSRe immunization with additional 3 doses series

MANAGEMENT OF BABIES BORN TO HBSAge+VE MOTHERS

• Safe delivery• Baby should receive HBIG 0.5ml I/M as soon

as possible but within 7 days of birth• Baby should be given 1st dose of Hep B vaccine

if baby weight is over 2 kg and if <1kg after 1 month

• Remaining doses of HBV can be given alone or in combination

HEPATITIS A VACCINE• Inactivated Hep A given in 2 doses starting from 1

year and 2nd dose 6 months after 1st dose• Doses are 720 ELU 1 -18 year of age• And 1440 ELU 19 years and older• For post exposure prophylaxis(contact with near and

dear ones) • IG(0.02ml/kg) given within 2 weeks after exposure

and is effective upto 85% in preventing Hep A upto 3 months

• Twinrix a combination vaccine of Hep A and Hep B for age 18 years and above

MEASLES• Measles is immunosuppresive disease associated

with chronic mortality, morbidity and serious complications

• Measles vaccine is a live attenuated and is available as a monovalant and also in combinations (MMR , MMRV)

• Pakistan being endemic state for measles , recommendation for measles are

• 1) measles at 9 months of age (MMR)• 2)MMR/MMRV at 15 months and at 4-6 years of

age

• Serum antibodies develop in 95% if MMR given at 12 months of age and 99% if given at 15 months of age

• Adverse effect are • Fever 5-15%• Transient rash• Thrombocytopenia• Encephalitis <1/million doses• For prevention of measles to close contacts IG

0.25 ml /kg can be given

VARICELLA VACCINE• Contains live attenuated vaccine as a monovalent

and part of MMRV • Dose is 0.5ml/s/c• 1st dose12-15 months and 2nd dose 4-6 years

(minimum interval between 2 doses is 3 months)• Single dose efficacy is 70-90% against infection

and 95%against serious infection. Recipients of 2 doses are 3.3 fold less likely to have break through infection. Duration of immunity is 20 yrs or more.

• Vaccine is safe and reactions are mild.

Haemophilus Influenza type B (HIb)• HIb conjugated vaccine consist of capsular

polysaccharide , Tetanus toxoid (PRP-T)/outer membrane protein complex from N.meningitidis.

• Available as a monovalent vaccine (ACT-HIB, HIBERIX).• 3 doses given at 2,4 and 6 months of age PRP-T, PRP-

OMP (minimum 2 doses interval being 1 month), 4th dose at 12-15 months

• Doses 0.5ml/IM• In patients with sickle cell disease , leukemia, HIV

infection, patients with splenectomy one dose of HIb vaccine may be given after age of 5 years.

PNEUMOCOCCAL VACCINE

• Streptococcal pneumonia causes invasive bacterial infection like pneumonia, empyema, AOM, meningitis etc

• 110 serotypes of pneumococci are identified• Two types of vaccines • 1)pneumococcal conjugate vaccine which are

immunogenic from 6 weeks -5years of age(PCV)• 2)pneumococcal polysaccharide 23 valent vaccine

which is immunogenic after the age of 2 years(PPSV23)

• Pneumococcal conjugate vaccine are available 10(synflorix) and 13(prevenar13) serotypes

• Primary series consists of three doses at 2 ,4 and 6 months of age and booster at 12-15 months of age

• Conjugate vaccine is recommended upto the age of 17 years and in all persons above 50 years.

• Doses 0.5ml I/M

PCV Q13 (CONJ) VERSUS PPSV23(PR POLYSACCHARIDE VACCINE

PCV13(CONJ) PPSV23(PR.POLYSACCHARIDE VACCINE)

DURATION OF IMMUNITY definite Unknown, likely to be short

IMMUNOLOGIC MEMORIES yes no

BOOSTER EFFECT WITH SUBSEQUENT DOSES

yes no

NASOPHARYNGEL EFFECT(HERD IMMUNITY)

yes no

ROTA VIRUS VACCINE • Incidence is 28-30% of all diarrhoeal diseases• 7 distinct groups are recognized A-G• Group A virus -major cause• Previously Rota virus vaccine was associated with

intussusception so it was withdrawn • In 2008 a live oral human attenuated rota virus vaccine

has been introduced as a two dose vaccine • Min age of 1st dose 6weeks• Max age of 1st dose 14 weeks and 6 days• Min interval between doses is 4 weeks• Max age of last dose 8 months

TYPHOID VACCINE• Effective 50-70%only• TAB vaccine can be given at age of 6 months• 3 doses are needed at 1-2 weeks interval (not in

use now because of severe local and side effects)• Ty21 A is live attenuated vaccine replicates in gut • It should not be used in acute gastroenteritis• Antibiotics should not be used 1 day prior and 7

days after 4th dose of vaccine• Should not used in immuno-compromised patients

vaccine type route Age of recipient

doses frequency

ViCPS(Typhim/Typherix)

polysaccharide

I/M 2years 1 2 years

Ty21a(Vivotef)

Live attenuated

oral 6 years 4 5 years

HUMAN PAPPILOMA VIRUS• Produce benign epithelial proliferation(warts) of skin and

mucous membranes• Also associated with anogenital dysplasia and cancers• HPV VACCINES quadrivalent (HPV4 types 6,11,16,18)

vaccines (Gardisil) is available• 3 doses starting from age of 11-13 years upper age limit is

26 years• Dose is 0.5 ml I/M 2nd dose 2 months after 1st dose and 3rd

dose 6 months after 1st dose• Ceravarix (bivalent HPV 2 for type 16,18)• 99% is immunogenic and has efficacy against cervical,

vulvar,vaginal cancers genital and skin warts • Now AIP has recommended quadrivalent for both sexes and

bivalent only for females.

INFLUENZA• Very common disease• Associated with fevers chills headache myalgia and

cough often super added by bacterial infection• Occasionally febrile seizures and encephalitis• Influenza virus is of 3 types (A,B,C). Epidemics is

caused by type A and B and both are included in influenza vaccine. Type C causes mild and sporadic disease and not included in the vaccine

• Circulating Human Influenza A subtypes include H1N1, H1N2 and H3N2 viruses.

Seasonal epidemics

• Are caused by minor antigenic variations within influenza A and B virus and are called antigenic drift

• Pandemics are caused by major changes in influenza A virus and are called antigenic shifts

• In 1918 H1N1 pandemic 20 million people were killed in USA and 50 million in the whole world.

Diagnosis• High index of clinical suspicion • Nasopharyngeal or oropharyngeal tissue swab obtained

within 72 hours of illness• 1)viral culture (result available in 2-6 days)• 2)Rapid diagnostic test for identification infective antigen

are available commercially- yields result in 30 mins• 3)direct florescent antibody(DFA) and indirect

immunoflorescent antibody (IFA) for the detection of infective antigen (results in 3-4 hours)

• PCR(higher sensitivity and specificity but lacks availability)

Types of vaccines

• Two types• Live attenuated influenza vaccine contain 3 virus

strains A(H3N2), A(H1N1)and B. It is used above 2 years through intranasal route

• May increase wheezing and may not be used in asthma and immuno-compromised patients

• Trivalent inactivated influenza vaccine is available with the names of Vaxigrip, Agrippal, Fluarix

SCHEDULE FOR TIV VACCINEAGE DOSE(ml) NO OF DOSE ROUTE

6-35 MONTHS 0.25 2 I/M

3 THROUGH 8 YEARS

0.5 2 I/M

9 YEARS OR OLDER 0.5 1 I/M

Timings for vaccine is October to January Indications• All children 6 months to 18 years• Household contact and children caretakers

Indication for persons above 19 years of age– Imuno-compromised states– Hemoglobinopathies– Chronic pulmonary and cardiac diseases– Chronic renal disease and metabolic diseases– Patient on long term salicylic therapy – All persons above 65 should be vaccinated once a

year.

COMBINATION VACCINES• DPaT- INFANNIX RS 1000• MMR PRIORIX/TRIMOVAX RS 600• HEP B ENGERIX/ENVAX RS220• DPT+HBV TRITANRIX RS 350• DPwT+HIB TETRAActHIB RS 1150• DPwT+HIB+HEPB PENTAVALENT RS 500 also available in Govt

setups• DPaT+HIB+IPV PENTAXIM RS 2000• DPaT+HIB+HBV+IPV INFANRIX HEXA RS 1750• 10 VALENT PNEUMOCOCCAL CONJ VACCINE SYNFLORIX RS 4000• 13 VALENT PNUEMOCOCCAL CONJ VACCINE PREVENAR RS 5330• ROTA VIRUS VACCINE ROTARIX RS 2900 • INFLUENZA VACCINE AGRIPPAL ,FLUARIX ,VAXIGRIP RS 600

approx

Dr. Abdul MalikMBBS, DCH, MCPS (PEADS) M.DPediatric consultant