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    Vaccines in childrenWhat they are

    How they workN. IagruAssociate Professor of Pediatrics

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    A short history(What Do Cows to Do with Vaccines?)

    The word vaccine comes from Latin vaccinuswhich meanspertaining to cows

    Edward Jenner (more than 200yrs ago), a

    country physician, noticed that milkmaids rarelysuffer from smallpox. Jenner took a few drops offluid from a skin sore of a woman who hadcowpox ( a related but far less serious disease),

    and injected the fluid into the arm of a healthyyoung boy who never had cowpox or smallpox.

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    Six weeks later, Jenner injected the boy with fluidfrom a smallpox sore, but the boy remained free of

    smallpox

    Dr. Eduard Jenner

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    The modern vaccine

    A preparation of proteins,polysaccharides, or nucleic acids ofpathogens that are delivered to the

    immune system as single entities, aspart of complex particles, or by live-attenuated agents or vectors, to

    induce specific responses thatinactivate, destroy, or suppress thepathogen

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    Public Health

    Vaccines are crucial to maitaining publichealth:

    Vaccines are safe, cost-effective, and

    efficient way to prevent sickness anddeath from infectious diseases

    Vaccines has lead to some of the greatestpublic health triumphs ever, including the

    eradication of naturally occurring smalpoxfrom the globe and the near eradication ofpolio

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    Variola virus

    Which causes smallpox, was once thescourge of the world

    This virus passes from person to person

    trough the air : fever, severe aches andpains, scarring sores that cover the body,blindness, and, often,death

    In the 18th

    century, variola killed every 7th

    child born in Rusia and every 10th inSweden and France

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    Naturally acquired immunity

    Before vaccines, the only way to becomeimmune to a disease was to actually get it, and,with luck, survive it (naturally acquiredimmunity)

    This means to suffer the symptoms of thedisease and also the risk of complications, whichcan be quite serious or even deadly

    On the other side, the patient may bycontagious and pass the disease to familymembers, to friends and to colleagues

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    Vaccination against variola

    WHO:1950/50million killed people

    1967/10-15 million killedpeople

    1977: the last case of naturally

    occurring smallpox was in

    Somalia

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    Diphteria

    1900, USA: diphteria killed more than cancer did

    Corynebacterium diphteriae : upper airwayinfection with a grayish, thick membrane that

    grows in the throat and obstructs breathing,fever, hoarseness, and coughing

    Deaths not only by blocked airways but from theparalyzing toxin secreted by the bacterium,which can cause heart or other organs to fail

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    Infectious poliovirus

    USA, till 1954: polio crippled 13,000 to20,000 people every year

    1954, before the first polio vaccine:18,000 cases of paralizing polio in USA

    Just 3 year later: 2,500/yr

    2006, WHO: 2,000 cases worldwide

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    Statistica in Romania

    1957-1961 1987-1991 Scadere (%)

    cazuri decese cazuri decese cazuri decese

    Poliomielita 1531 889 74 2 99,3 99,9

    Difterie 3982 319 9 1 99,7 99,6

    Tetanos 4224 1843 144 65 96,5 99,7

    Pertussis 448.882 663 10.413 22 97,6 96,6

    Rujeola 513.547 860 23.976 25 95,3 97,1

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    Active ImmunisationArtificially acquired immunity

    Vaccinations or immunizations (hardcore of primary profilaxy) are,generally speaking, interchangeableterms ( active immunisation!)

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    Active immunization 2

    Vaccination is administration of anyvaccine (inactivated or killed wholeorganisms or a part from an

    organism), toxoid (inactivated toxin),or of a specific recombinant productin order to produce an immune

    response similarly to those fromnaturally infection.

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    To become immune

    Once the immune system is trainedto resist a disease, the person aresaid to be immune to it

    Is provided by vaccines and are aneasier and less risky way to becomeimmune

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    Herd immunity

    Vaccines protect not only yourselfbut also others around you

    Similarly, when other people arevaccinated, they are less likely togive the disease to you

    So, vaccines protect not onlyindividuals, but entire communities

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    Community immunity

    If a critical number of people withina community are vaccinated againsta particular ilness, the entire group

    becomes less likely to get thedisease.

    This protection is called community

    immunity, or herd immunity

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    Community immunity: if enough people in a community arevaccinated against a particular ilness, the entire group becomes lesslikely to get the disease, even those who are not vaccinated

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    x

    x x

    Efectul indirect / Herd protection:Populatia vaccinata partial

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    Passive immunity

    Immunity transferred from oneperson to another:

    - antibodies passed from mothers beforebirth or through breastfeeding protect thebabies against some diseases

    - purified blood serum which contains theantibodies produced after someonesuffered from an ilness in the past

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    Passive immunization II

    Involves also the administration ofpreformed antibody in the form ofintramuscular immunoglobulin, intravenousimmunoglobulin, or concentrated monoclonalantibodies (Palivizumab for RSV)

    Indications: after high-risk exposure toindividuals not immunized against the disease inquestion; high-risk of severe complications(children born to women who are chroniccarriers of hepatitis B surface antigen); PID

    ( replacement IVIG)

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    Passive Immunization Products

    Rabies immune globulin

    Tetanus immune globulin

    Diphteria antitoxin(horse serum derived)

    Hepatitis B immune globulin

    Cytomegalovirus immune globulin I.V.

    Varicella-zoster immune globulin

    I.V.I.G.(PID)

    Botulism immune globulin I.V.

    Immune globulin for prevention of Hepatitis A inunimmunized individual after exposure

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    Types of vaccines

    Live, Attenuated Vaccines

    Inactivated Vaccines

    Subunit Vaccines Toxoid Vaccines

    Conjugate Vaccines

    DNA Vaccines

    Recombinant Vector Vaccines

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    Live, Attenuated Vaccines

    Contain a version of the living microbe that havebeen weakened (attenuated) in the lab so itcant cause disease

    Because a live, attenuated vaccine is the closestthing to a natural infection, these vaccines aregood teachers of the immune system: theyelicit strong cellular and antibody responses, and

    often confer lifelong immunity with only one ortwo doses

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    I. Live, attenuated vaccines

    This image shows the live microbes antigens,

    membrane, and genetic material

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    Downsides

    The organisms used in live, attenuated vaccinescan change or mutate ( is the nature of livingthings to change!), and could revert to a virulentforme and cause disease

    Persons with damaged or weakened immunesystems (PID, HIV, chemotherapy)

    Need to be refrigerated to stay potent(the

    shipping overseas and stored by health careworkers in developing countries that lackwidespread refrigeration)

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    Live, attenuated

    Are relatively easy to create for certainviruses (contain a small number of genes):

    -measles, rubella,polio (Sabinvaccine),mumps chickenpox,yellow fever

    Are more difficult to create for bacteria(have thousands of genes, much harder to

    control): vaccine against Vibrio cholerae

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    II. Inactivated Vaccines(killed vaccines)

    By killing the disease-causing microbe withchemicals,heat, or radiation

    Are more stable and safer than live vaccines(the

    dead microbes cant mutate!) Dont require refrigeration ( can be easily stored

    and transported in a freeze-dried form)

    Stimulate a weaker immune system responsethan live vaccines (need booster shots, thatcould be a drawbackin developing areas !)

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    Exemples for inactivated vaccines

    V. bacteriene inactivate : DTPa sauDTPw, HI tip b, meningococic(A,C,Y,W135), cholera, plague

    Vaccinuri viraleinactivate: Flu,VPI(Salk vaccine), hepatita B, hepatita A,

    rabies,Japanese encephalitis.

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    Inactivated vaccines

    Inactivated vaccines contain microbes that have beeninactivated with chemicals, heat, or radiation. Themicrobes antigens, membrane, and genetic material arestill present.

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    III. Subunit vaccines

    Instead of entire microbe, subunit vaccinesinclude only the antigens that best stimulate theimmune system

    In some cases, Subunit Vaccines use epitopes(the very specific parts of the antigen) thatantibodies or T cells recognize and bind to

    Because SUV contain only the essential antigens

    (1-20 or more antigens) and not other moleculesthat make up the microbe, the risks of adversereactions to the vaccine are lower

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    Subunit vaccines

    The imagine depicts antigens that have been separated

    from the rest of the microbe for use in a subunit vaccine

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    Subunit Vaccines

    SUV are vaccines produced by recombinanttechnology

    They are called Recombinant Subunit Vaccines :

    - vaccine against hepatitis B virus

    Scientists inserted hepatitis B genes that code forimportant antigens into common bakers yeast

    The yeast then produced the antigens, they arecollected and purified for use in the vaccine

    Other vaccines: pertussis, pneumonia caused byS.pneumoniae

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    IV. Toxoid vaccines

    They are used when a bacterial toxin isthe main cause of illness

    Toxins are inactivate by treating themwith formalin (a solution of formaldehydeand sterilized water)

    Detoxified toxins are called toxoids and

    they are safe for use in vaccines

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    Toxoid Vaccines

    Harmless toxoid molecules (artists representation) are used in

    toxoid vaccines to immunize and protect people against harmfultoxins secreted by some microbes

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    Toxoid Vaccines

    The immune system producesantibodies that lock onto and blockthe toxin

    Exemples of toxoid vaccines:

    - Vaccine against diphteria

    - Vaccine against tetanus

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    V. Conjugate Vaccines

    Are used against bacteria which possessed anouter coating of sugar called polysaccharides

    Polysaccharide coating disguise a bacteriumsantigens so that the immature immune systems

    of infants and younger children cant recognizeor respond to them Scientists link antigens or toxoid from a microbe

    that an infants immune system can recognize,

    to the polysaccharides. The linkage helps the immature immune systemreact to polysaccharide coating and defendagainst the disease-causing bacterium

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    Conjugate vaccines

    Conjugate vaccines link antigens or toxoids to the polysaccharid or sugar moleculethat certainbacteria use as a protective coating,thereby allowing the immune system to recognize and attackthes disguised bacteria. A conjugate vaccine contains the molecules shown in the foreground.The bacterium, part of which is shown in the upper left background, is not part of the vaccine.In fact, this kind of vaccine is a subunit vaccine

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    Exemples of Conjugate Vaccines

    Vaccine against HI b

    Vaccine against Streptococcuspneumoniae: Prevenar 7 valent

    Prevenar 13 valent

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    VI. DNA Vaccines

    Experimental stages ! (but several typesalready tested in humans)

    DNA vaccines take immunization to a new

    technological level Dispense with both the whole organism

    and its parts and get right down at the

    essentials: the microbes genetic material DNA vaccines use the genes that code for

    those all-important antigens

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    DNA Vaccines II

    When the genes for a mirobesantigens are introduced into thebody, some cells will take up that

    DNA

    The DNA then instructs those cells tomake the antigen molecules

    The cells secrete the antigens anddisplay them on their surfaces

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    DNA Vaccines

    In other words, the bodys own cellsbecome vaccine-making factories,creating the antigens necessary to

    stimulate the immune system

    DNA vaccines are relatively easy and

    inexpensive to design and produce

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    DNA Vaccines

    DNA vaccines use a microbes genetic material, in particular, the genesthat code for important antigens. The DNA in these vaccines is a circular

    form known as a plasmid

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    DNA Vaccines III

    SO-called naked DNA vaccines consist ofDNA that is administered directly into thebody

    These vaccines can be administered with aneedle and syringe or with a needle-lessdevice that uses high-pressure gas toshoot microscopic gold particles coatedwith DNA directly into cells

    Tested in humans: influenza, herpes, HIV

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    VII. Recombinant Vector Vaccines

    These experimental vaccines are similar toDNA vaccines, but they use an attenuatedvirus or bacterium to introduce microbial

    DNA to cells of the body

    Vectors refers to the virus or bacteriumused as a carrier

    In nature, viruses latch on the cells andinject their genetic material into them

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    Recombinant Vector Vaccines II

    In the lab, scientists have takenadvantage of this process.

    They figured out how to take the

    roomy genomes of certain harmlessor attenuated viruses and insertportions of the genetic material fromother microbes into them

    The carrier viruses then ferry thatmicrobial DNA to cells

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    Recombinant Vector Vaccines III

    They closely mimic a natural infection andtherefore do a good job of stimulating theimmune system

    Attenuated bacteria as vectors : the

    inserted genetic material causes thebacteria to display the antigens of othermicrobes on its surfaace.

    In effect, the harmless bacterium mimics aharmful microbe provoking an immuneresponse

    Researches: vaccines for HIV, rabies, andmeasles

    R bi V V i

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    Recombinant Vector VaccinesRecombinantvector vaccines use the harmless shell of one microbe. The

    genetic material contains the code for marking vaccine antigen inside some of

    the bodys cells, using those cells as factories

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    Reportable events after vaccinations

    Anaphylaxis or anaphylactic shock,brachial neuritis and theirsequela(DTP, DTPHiB)

    Idem, Encephalopathy(orencephalitis):MMR; chronic arthritis(rubella in any combination);Thrombocytopenic purpura (measlesin any combination); Paralytic polio(OPV); Intussusception (Rotavirus).

    Romanian National Program for

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    gImmunization

    (Calendarul de vaccinare 2009)

    Varsta recomandata Vaccin ComentariiPrimele 24 ore

    2-7 zile

    Hep. B

    BCG

    In maternitate

    2 luni DTP, VPI, Hep. B Simultan

    4 luni DTP, VPI Simultan

    6 luni DTP, VPI, Hep. B Simultan

    12 luni DTP, VPI,

    RRO(MMR)

    Simultan

    4 ani DTaP*

    7 ani (cls.I) RRO (MMR) Campanii scolare

    9 ani (cls. a III-a) VPI Campanii scolare

    14 ani (cls. a IV-a) dT Campanii scolare

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    U.S. Vaccine-Preventable InfectiousDiseases

    Anthrax, Bacterial meningitis, Chickenpox,Diphteria,Haemophilus influenzae typeb,Hepatitis A, Hepatitis B, Cervical

    cancer(HPV),Influenza, Japaneseencephalitis,Measles, Mumps, Pertussis,Pneumococcal pneumonia, Polio, Rotavirusdiarrhea, Rabies, Rubella, Smallpox,

    Shingles, Tetanus, Tuberculosis,Typhoid,Yellow fever

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    Programul national de imunizare (PNI)

    Absente notabile fata de PNI-urile din tariledezvoltate din UE si din SUA :

    Vaccinarea anti-HI tip b

    Vaccinarea antipneumococica

    Vaccinarea anti-Rotavirus

    Vaccinarea anti-varicela

    Vaccinarea anti-meningococica

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    U.S.Routine Immunization Schedule

    American Academy of Pediatrics

    American Academy of Family Phisicians

    Advisory Committee on Immunization

    Practices of the Centers for DiseasesControl and Prevention (CDC)

    jointly prepare and updated immunizationschedule every January, which is published inthe Pediatrics, Morbidity and MortalityWeekly Reportand in Family Physician

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    Contraindications

    For children with intact immunesystem there are few absolutecontraindications to receiving the

    first dose of any vaccine ! Inactivated or subcomponent

    vaccines pose no additional risk topatients with immune deficiency

    disorders, but some patients may notbe protected from the target disease

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    Contraindications

    Immediate Hypersensitivity Reactions( Anaphylaxis or angioedema after a previous dose ofvaccine is usually a contraindication for the subsequentdoses of the same vaccine)-Vaccines produced in the chick embryo tissue culturesdo not contain detectable amounts of egg proteins-Some of hypersensitivity reactions are caused bycomponents added to vaccines( the gel stabilizer inmeasles vaccine)

    - The mild allergic reactions are not a contraindication toreceive the subsequent doses, but may require specialinvestigations and a consult with an allergist or vaccinesafety specialist

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    Encephalopathy or Encephalitis

    Both of them, within a few days after DTP vaccineadministration is a contraindication to receipt ofthe subsequent doses

    A febrile seizure after any vaccine is not acontraindication to receipt a subsequent doses of

    vaccine were other vaccines that might inducefever

    Children who have had encephalitis orencephalopathy of unknown cause unrelated toimmunization can safely receive all recommended

    vaccines if neurologic condition is stable Children with progressive neurologic disorders

    should defer the DTaP vaccine until the conditionis stable

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    Immune Deficiency Disorders

    Live vaccines can cause serious adverseevents in patients with immune deficiencydisorders (i.e risk of vaccine-associatedparalysis after OPV is increased at least

    1,000-fold in persons withagammaglobulinemia) Patients with HIV infection can receive live

    MMR or varicella vaccine if their CD4 countis greater than 15%

    Other patients with primary or acquireddeficiency of T cells generally should notreceive live viral vaccines

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    Immune deficiency Disorders II

    Some patients can safely receive live vaccines:- Patients successfully treated for cancer can be

    usually be immunized with both live andinactivated vaccines after completion ofchemotherapy, but specific waiting times are

    recommended- Mild immune deficiency disorders, such a

    subclass IgG deficiency disorders, are notassociated with adverse events followingvaccination

    - Patients with disorders of white blood cellfunctions (CGD), can receive all inactivated

    varicella and live viral vaccines

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    Other contraindications

    Severe ilnesses ( infectious diseases,TBC evolutiva, chronic nephropaty,chronic liver diseases, severe

    cardiovascular diseases) Cachexy

    Pregnancy,live vaccines are

    prohibited in the first 3 monthsbecause they may be teratogenic.

    N t i di ti d

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    Noncontraindications andMisconception

    Children with mild upper respiratory infections orgastroenteritis can receive routine immunizationsas there is no evidence of any increased risk fromvaccinationof children with these infections

    Low-grade fever-less than 39C-is not acontraindication to immunization ! ( Although, ismore prudent to wait for a few days to beimmunized if uncertainty exists regarding the

    cause of the concurent ilness)----------------------------------------------------------Neal A.Halsey. Immunization. Oskis Pediatrics Principle &Practice, 2006:118-134

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    Some specific immunizing agents

    Meningococcal Vaccine :1.A plain polysaccharide vaccine against Neisseriameningitidestypes A,C, Y, and W135 in children 2 ormore years of age, recommended for children atincreased risk of disease including those with asplenia or

    complement deficiency. It is not administered routinelyto children because the risk of disease is relatively low2.A polysaccharide-protein conjugate vaccinecontaining types A, C, Y, and W135 (2005) for allchildren 11-12 years of age, for previously

    unvaccinated 15-16 yr old, college freshman living indorms, and others at high risk of disease

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    Vaccine strategies

    Some vaccines come incombinations:

    DTP, MMR

    Combination vaccines reduce visit tothe doctor, saving time and moneyand sparing children extra

    needlestick

    V i C M th d S f t

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    Vaccine Concerns, Myths, and SafetyIssues on the Web

    Rumors and misinformation about vaccinesafety abound

    Now that vaccines have virtuallyeliminated many once-feared diseases,

    the possibility of vaccine side effects oradverse reactions loom larger in somepeoples minds than the diseases thatvaccines prevent

    Most parents today have never seen a caseof diphteria or measles, and some wonderwhy their children must receive so manyshots

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    Safety Issues

    Many parents are concerned thatmultiple vaccines may weaken or

    overwhelm an infants immunesystem or that certain vaccines maycause autism, multiple sclerosis, or

    diabet

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    Combination vaccines

    May they overwhelm or weaken childs immunesystem ?

    The immune system contains billion of circulatingB and T cells capable of responding to millions of

    different antigens at once Because the body constantly replenishes these

    cells, a healthy immune system cannot be usedup or weakened by a vaccine

    According to one published estimation, infants

    could easily handle 10,000 vaccines at once !

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    Further reading

    http://www.cdc.gov/vaccines/schedules/

    http://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htm

    http://www.cdc.gov/vaccines//vpd-vac/vaccines-list.htm

    http://www.cdc.gov/vaccines/schedules/http://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines//vpd-vac/vaccines-list.htmhttp://www.cdc.gov/vaccines//vpd-vac/vaccines-list.htmhttp://www.cdc.gov/vaccines//vpd-vac/vaccines-list.htmhttp://www.cdc.gov/vaccines//vpd-vac/vaccines-list.htmhttp://www.cdc.gov/vaccines//vpd-vac/vaccines-list.htmhttp://www.cdc.gov/vaccines//vpd-vac/vaccines-list.htmhttp://www.cdc.gov/vaccines//vpd-vac/vaccines-list.htmhttp://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines/vpd-vac/vpd-vac-basics.htmhttp://www.cdc.gov/vaccines/schedules/
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    List of Vaccine-Preventable

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    List of Vaccine-PreventableDiseases [1]

    Anthrax Cervical Cancer (Human

    Papillomavirus) Diphtheria Hepatitis A Hepatitis B Haemophilus influenzae

    type b (Hib) Human Papillomavirus

    (HPV) Influenza (Flu) Japanese encephalitis

    (JE)

    Lyme diseaseLyme disease vaccine nolonger available in theUnited States.

    Measles

    Meningococcal Monkeypox

    There is NO monkeypoxvaccine. The smallpoxvaccine is used for this

    disease. Mumps Pertussis

    List of Vaccine-Preventable

    http://www.cdc.gov/vaccines/vpd-vac/anthrax/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hpv/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/diphtheria/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hepa/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hepb/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hib/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hib/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hib/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hpv/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/flu/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/j-enceph/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/lyme/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/measles/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/mening/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/monkeypox/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/mumps/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/pertussis/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/pertussis/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/mumps/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/monkeypox/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/mening/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/measles/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/lyme/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/j-enceph/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/flu/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hpv/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hib/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hib/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hib/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hepb/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hepa/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/diphtheria/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/hpv/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/anthrax/default.htm
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    List of Vaccine-PreventableDiseases [2]

    Pneumococcal

    Polio

    Rabies

    Rotavirus Rubella

    Shingles (Herpes

    Zoster) Smallpox

    Tetanus

    Typhoid

    Tuberculosis (TB)

    Varicella (Chickenpox)Yellow Fever

    http://www.cdc.gov/vaccines/vpd-vac/pneumo/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/polio/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/rabies/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/rotavirus/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/rubella/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/shingles/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/smallpox/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/tetanus/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/typhoid/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/tb/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/varicella/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/yf/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/yf/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/varicella/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/tb/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/typhoid/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/tetanus/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/smallpox/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/shingles/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/rubella/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/rotavirus/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/rabies/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/polio/default.htmhttp://www.cdc.gov/vaccines/vpd-vac/pneumo/default.htm