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חיסונים בגיל הילדותחיסונים בגיל הילדות
פרופסור יהודה דנון
מרכז שניידר לרפואת ילדים[email protected]
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
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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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