חיסונים בגיל הילדות

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חיסונים בגיל הילדותחיסונים בגיל הילדות

פרופסור יהודה דנון

מרכז שניידר לרפואת ילדיםydanon@post.tau.ac.il

הרצאה בי"ס לרפואה

2007מאי

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Aims & objectives of immunizationAims & objectives of immunization prevention of serious diseases and their

complications protection of individuals and communities containment of outbreaks elimination of certain diseases, e.g. tetanus eradication of diseases, e.g. smallpox (1980) &

polio (target date 2005)

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World situationWorld situation

World Health Organization (WHO) - Expanded Programme on Immunization (EPI) 1974

six target diseases: diphtheria, tetanus, pertussis, polio, measles & tuberculosis

inequity to vaccination programmes: R&D & funding of new & existing vaccinesimmunisation safetyState of the World’s Vaccines and Immunization, WHO, 2002

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Decisions to introduce a vaccineDecisions to introduce a vaccine

is the disease important enough? can a safe and effective vaccine be produced? is it acceptable to recipients, their parents or

carers? is it cost effective? can enough people in the target group be

immunised to make the programme effective?

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Different types of vaccinesDifferent types of vaccines

Inactivated vaccines:killed whole organisms e.g. pertussisinactivated bacterial toxins, e.g. diphtheria & tetanusacellular vaccine e.g. pertussis

Polysaccharide vaccinesplain polysaccharide e.g. pneumococcal for over 2spolysaccharide conjugate e.g. Hib, MenC

Live attenuated e.g. MMR, polio & BCG Combination vaccines e.g. DTP-Hib, MMR

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Development of safe, effective vaccinesDevelopment of safe, effective vaccines

Pre-clinical trials volunteers and protocols clinical trials

Phase I studiesPhase II studiesPhase III studies

licensure immunisation policy

Monitoring vaccine safety Monitoring vaccine safety

routine testing before releasePhase lV studies - Post-Licensing

Evaluation“Yellow card” system studies of vaccine safety

cohort studiescase-control studiesrecord linkage

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Contraindications & precautions Contraindications & precautions

Contraindications: severe local or systemic reactions to preceding doseslive vaccines because of disease temporary contraindications: live vaccines in the immunosuppressed due to treatment - chemotherapy, radiotherapy, high dose corticosteroids, organ transplantation with concurrent & immunosuppressive treatment

Precautions:increased risk of reaction or compromised immunity

Adverse eventsAdverse events

all medicines, including vaccines can cause adverse events

three general categories:localsystemicallergic

real v myth

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Benefits and risksBenefits and risks

the benefit of the vaccination outweighs the risk of the disease and associated morbidity and mortality

the risk of adverse events to an immunization outweighs the risk of the disease and associated morbidity and mortality

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Successful immunisation Successful immunisation

production of a safe and effective vaccinemaintaining cold chain from point of

manufacture to administration ordering and storageconsentinjection into correct site using the correct

techniqueImmune response in individual

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Public & professional knowledgePublic & professional knowledge

Bi-annual tracking of mothers:knowledge about immunisationattitudes towards immunisationexperience of immunisation servicesresponse to advertising using key indicators

annual health professional survey:impact of publicityawareness & evaluation of materialsassessing the needs of GPs, practice nurses & health visitors

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InformationInformation

Resources:leaflets, factsheets, FAQs, websites, green book, posters, videosprofessional mailings - CMO letters/updates

Advertising: TV & radio, parent and professional journals, newspapers

press & public relations

Professional responsibilityProfessional responsibility

responsibility of being reliably informedresponsibility of not just simply

providing the facts, but of our own informed opinion and support for immunisation

responsibility for promoting immunisation as the most important of all medical interventions

It is every child’s right to be protected against infectious disease. No child should be denied immunisation without serious thought as to the consequences, both for the individual child and for the community

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Factors influencing the immune response to Factors influencing the immune response to vaccinationvaccination

Presence or absence of maternal antibodies

Nature and dose of antigen administratedMode of administration of vaccineAdjuvant

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Dynamics of antibody formationDynamics of antibody formation

Primary immune response1. Latency period

2. Growth period

3. Period of decline

Secondary response

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Viral vaccinesViral vaccines

Live attenuated vaccines: Oral poliomyelitis (OPV), Measles, Mumps, Rubella, Yellow fever

Inactivated vaccines: Influenza, Rabies, Injectable poliomyelitis (IPV)

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Bacterial vaccinesBacterial vaccines

Live attenuated: BCGKilled vaccine: pertussis, typhoid,

choleraToxoid: Diphteria, TetanusPolysaccharide vaccines: Meningococcal

Atc. Pneumococcal

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Vaccines produced on embryonic eggs or Vaccines produced on embryonic eggs or chick embryochick embryo

Influenza vaccineYellow fever vaccineMeasles vaccineMumps vaccine

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Diphtheria ImmunizationDiphtheria Immunization

The immunizing antigen is toxoid prepared by corynebacterium diphteriae toxin

Provided in combination with Tetanus– DT

– Td

– DTaP

– DTP

Aluminium hydroxide as adjuvant

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Tetanus ImmunizationTetanus Immunization

Neurotoxicity by a potent exotoxin of Clostridium tetanii (spore)

Common circumstances:– Contamination of the umbilicus of neonate– Wounds that result with pockets of

anaerobiosis– Insect bites– Contamination of surgical wounds

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Immunizing Agent-TetanospaminImmunizing Agent-Tetanospamin

The toxin of C. Tetanii is modified by chemical treatment to provide a stable non toxic toxoid– T– DT– Td– DTaP

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Pertussis ImmunizationPertussis Immunization

Classical pertussis vaccine; killed whole Bordetela pertussis inducing fragments of the organism

New pertussis vaccines composed of purified components of B. pertussis prepared from inactivated organisms acellular pertussis vaccine (aP)– aP– TaP– TDap

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Poliomyelitis ImmunizationPoliomyelitis Immunization

Inactivated poliovirus vaccines;

A polyvalent vaccine containing formalin inactivated poliovirus types 1,2 and 3 grown on monkey kidney tissue culture (Salk, 1955) – IPV

Since 1988 production in human diploid cells

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Attenuated oral poliovirus vaccineAttenuated oral poliovirus vaccine

Trivalent OPV (TOPV) is a mixture of polioviruses types 1,2, and3 grown on monkey kidney cells in t.c. or human diploid cell in t.c. (Sabin, 1961)

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Measles in Israel

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Measles (Rubeola) ImmunizationMeasles (Rubeola) Immunization

Killed measles vaccine (KMV) (Fulginiti, 1963) Live measles virus vaccine

– Edmonston strain (1963)– Schwartz strain (1964)

Passages of LMV in chick embryo tissue culture– LMV– MMR– MM– MR

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Mumps ImmunizationMumps Immunization

Mumps virus (Jerryl Lynn strain)Attenuated by passage in chick embryo

tissue culture (1967)– M– MMR

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Rubella Rubella (German meals)(German meals) immunization immunization

Live attenuated rubella virus grown in chick embryo tissue culture– Monovalent R– Monovalent MR– Monovalent MMR

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Hemophylus Influenza Type B immunizationHemophylus Influenza Type B immunization

Hib leading cause of bacterial meningitisMore then 90% of meningitis cases from

Hib occur in children younger then 5 years old

Peak attack rate in children 6-8 months old

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Hemophylis Type B polysaccharide vaccineHemophylis Type B polysaccharide vaccine

Purified Hib capsular polysaccharide polyribosyl-ridutol phosphatee (PRP)– PRP– PRP D– PRP DT– PRP DTaP

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Hepatitis B immunizationHepatitis B immunization

16,000 cases annually in the USA300-350 cases in Israel1% of cases associated with fulminant

disease and deathCirrhosishepatoma

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Hepatitis B immunizing antigenHepatitis B immunizing antigen

Recobinent hepatitis B vaccines are produced using Hepatitis B surface antigen synthesized by Sacharomyces cerevesiae into which a plasmid containing the hepatitis B surface antigen has been inserted

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Hepatitis A ImmunizationHepatitis A Immunization

Human derived virus strain H47-175 in human diploid cells in t.c. inactive with formalin preservative –2-phenoxyethanol

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Varicella virus immunizationVaricella virus immunization

About 3.9 million cases of varicella annually in the USA

Estimation of 80-100,000 cases occur annually in Israel (Abrahamy & Danon, 1999)

Varicella occurs typically in young children About 10% of adults susceptible to varicella

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Immunizing antigenImmunizing antigen

The vaccine is a cell free, live, attenuated preparation of the Oka strain of Varicella-Zoster Virus

Propagated in human diploid cell culture The vaccine is officious in adults and children one year of

age or older Zoster occurs with lower frequency after immunization

than after natural disease Single dose of 0.5ml of vaccine s.c. Individuals 13 years or older should receive two doses

separated by 4-8 weeks Varicella vaccine may be given simultaneously with MMR

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BCG VaccinationBCG Vaccination

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Recommendations for BCG VaccinationRecommendations for BCG Vaccination

Not recommended in immunization programs or TB control programs in the U.S.

BCG vaccination undertaken after consultation with health department

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Considered for an infant or child with negative skin-test result who Is continually exposed to untreated or ineffectively treated patient Will be continually exposed to multidrug-resistant TB

Recommendations for BCG Vaccination Recommendations for BCG Vaccination (cont.)(cont.)

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Recommendations for BCG Vaccination Recommendations for BCG Vaccination (cont.)(cont.)

Vaccination considered on individual basis in settings in which high percentage of MDR TB patients has been found Transmission of drug-resistant TB strains and subsequent infection are likely, and Comprehensive TB infection-control precautions implemented and not successful

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BCG ContraindicationsBCG Contraindications

Contraindicated in persons with impaired immune response from:

HIV infection Congenital immunodeficiency Leukemia Lymphoma Generalized malignancy Receiving high-dose steroid therapy Receiving alkylating agents Receiving antimetabolites Receiving radiation therapy

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BCG Vaccination and Tuberculin Skin TestingBCG Vaccination and Tuberculin Skin Testing

Tuberculin skin testing not contraindicated for BCG-vaccinated persons

LTBI diagnosis and treatment for LTBI considered for any BCG- vaccinated person whose skin test reaction is $10 mm, if any of these circumstances are present: Was contact of another person with infectious TB Was born or has resided in a high TB prevalence country Is continually exposed to populations where TB

prevalence is high

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Anthrax vaccineAnthrax vaccine

Currently recommended for individuals with professional susceptibility to Anthrax aerosol

Immunizing agent aluminum hydroxide absorbed concentrated off protective antigen prepared from non capsulated strain B. anthracis

Basic series of six 0.5ml injections given s.c.

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HEAL IL 26137 08.39 CH452782

PLEASE NOTE THAT WE STOP ROUTINE SMALLPOX VACCINATION ON 18/07/1980

CORINA COSTIN.

DEPARTMENT OF EPIDEMIOLOGY MIN OF HEALTH JERUSALEM.

28/08/1980AL I L.HE.613.7A OMS CH ?27821

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VaccineVaccine

Smallpox vaccine based on the Lister strain vaccinia virus grown on chorioallantoic membrane of fertilized eggs is produced by the Ministry of Health.

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Helicopter pipetteHelicopter pipette

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among First 20000 first responders Vaccinated

Fever - 8.1 % Headaches - 28 % Muscle pain - 22.5 % Nausea - 12 % Fatigue and weakness - 31 % Shivering - 12 % Other - 13 %

Side EffectsSide Effects

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Smallpox adverse eventsSmallpox adverse eventsCas

eAgeSexDate SymptomsDiagnosis

163F11.11.200218.11.2002Generalized vaccinia (contact)

255F11.09.200225.09.2002Polymayalgia

342M29.12.200208.01.2003Erythema multiforme

452F27.08.200207.09.2002Erythema multiforme

544F03.11.200217.11.2002Stevens Johnson Optic neuritis

645M01.01.200320.1.2003Peripheral neuropathy

94 Laboratory Acquired Vaccinia Virus

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ProMED-mail – 20.08.2002ProMED-mail – 20.08.2002

This will serve as a dry run for the American strategy,in terms of finding undesirable side effects and transmission to immunodeficient contacts. – Mod.JW

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Age and Age and vacciniavaccinia response responseMaleFemale

Age#% Take#% Take

>258155.623663.6

25-2920151.739151.2

30-3425957.149755.5

35-3927162.062961.7

40-4435962.484166.2

45-4936359.290762.3

50-5440063.393962.7

55-5921665.354066.5

<6016061.327269.5

Total231060.4525262.4

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Age of last vaccination and present Age of last vaccination and present vacciniavaccinia response response

# Vaccinated% Take

Infancy 18/12-24/1253359.7

First grade 6-7y76869.4

Army 18y84161.1

Other20557.1

Not Known525861.3

Total760561.9

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VIG- 2500 Lit. Hyper Immune PlasmaVIG- 2500 Lit. Hyper Immune Plasma

First batch Omrix- IVIG January 2003Exp. Date Dec. 2004Second Omigram production 2005-6

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Rabies vaccineRabies vaccine

Human rabies rare in Israel200-300 individuals each year require

prophylaxis, after known or potential exposure to rabbis

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Rabies vaccinesRabies vaccines

Human diploid cell vaccine (HDCV) Rabies vaccine absorbed (RVA) Purified chick embryo cell (PCEC) Active immunization for pre-exposure

prophylaxis in high risk groups Past exposure prophylaxis by a combination of

active and passive immunization with anti rabbis immune serum globulin (RIG)

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Simultaneous Administration of Multiple VaccinesSimultaneous Administration of Multiple Vaccines

Most vaccines can be safely and effectively administered simultaneously. No contraindications to the simultaneous administration of multiple vaccines routinely recommended for infants and children are known. Immune responses to one vaccine generally do not interfere with those to other vaccines. An exception is a decrease in immunogenicity when cholera and yellow fever vaccines are given together or 1 to 3 weeks apart. Simultaneous administration of IPV, MMR, varicella, or DTaP vaccines results in rates of seroconversion and of adverse effects similar to those observed when the vaccines are administered at separate visits.

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Simultaneous Administration of Multiple VaccinesSimultaneous Administration of Multiple Vaccines

Because simultaneous administration of common vaccines is nor known to affect the efficacy or safety of any of the recommended childhood vaccines, simultaneous administration of all vaccines, including DTaP, IPV; MMR, varicella, hepatitis A, hepatitis B, Hib, and pneumococcal conjugate and polysaccharide vaccines that are appropriate for the age and previous immunization status of the recipient, is recommended. When simultaneous vaccines are administered, separate syringes and sites should be used, and injections into the same extremity should be separated by at least 1 inch so that any local reactions can be differentiated. Simultaneous administration of multiple vaccines can increase immunization rates significantly. Individual vaccines should never be mixed in the syringe unless they are specifically licensed and labeled for administration in one syringe. For people preparing for international travel, multiple vaccines generally can be given concurrently.

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התרכיב מנות בין המותר המינימלי הזמן ורווח המינימום התרכיב גיל מנות בין המותר המינימלי הזמן ורווח המינימום גילבסדרהבסדרה

מרווח מינימלי בין דחף למנה

האחרונה בבסיס

מרווח מינימליבין מנות הבסיס

גיל המינימום למנה הראשונה

תרכיב

חודשים ולא לפני 6 חודשים12גיל

שבועות 6 שבועות4DTaP, DT,

Td *

IPV שבועות 6 שבועות4 חודשים6

OPV שבועות6 שבועות4 חודשים2

חודשים ולא לפני 2 חודשים12גיל

Hib שבועות6 שבועות4

אחרי לידה חודש1 חודשים 4 HBV

- חודש1 MMR חודשים**12

- חודשים6 HAV חודשים12

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Investigational active immunizing agentsInvestigational active immunizing agents

CMV vaccineVaccinia Ankara strainRotavirus vaccineGroup B streptococcal vaccineTularemia vaccineHIV vaccine

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Passive immunization agentsPassive immunization agents

Vaccinia immunoglobulin (VIG) Varicella Zoster Immunoglobulin (VZIG) Human immune serum globulin

– Hepatitis A prophylaxis– Measles prophylaxis

Special immunoglobulin preparations– HBIG– RIG– TIG– Cytomegalovirus IVIG– RSV-IGIV (Respyam)

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