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					 Childhood vaccination

 2008 Update

Jesse Papenburg, MD, FRCPC
Fellow, Pediatric Infectious Diseases &
Medical Microbiology
Montreal Children's Hospital
Immunization

   Ultimate goal: eradication of disease

   Immediate goal: prevention of
    disease in individuals or groups




               Childhood Vaccination   Feb 15 2007
   Baseline 20th Century Annual Morbidity and 2004
      Morbidity from 10 Diseases with Vaccines
    Recommended for Universal Use in Children: US

Disease         Baseline   2004 Morbidity   % Decrease

Smallpox        48 164          0                100
Diphtheria      175 885         2                >99
Pertussis       147 271         25827            82
Tetanus         1 314           34               97
Poliomyelitis
(paralytic)     16 316          0                100
Measles         503 282         37               >99
Mumps           152 209         258              >99
Rubella         47 745          10               >99
Congenital
rubella         823             0                100
Hib             20 000          196              >99
Active Immunization

   Administration of all or part of a
    microorganism or product to evoke
    an immunologic response
    mimicking that of natural infection

   Effectiveness = evidence of
    protection against natural disease


              Childhood Vaccination   Feb 15 2007
Passive Immunization
   Administration of pre-formed antibodies
       Immune globulin (IM)
       Hyper-immune globulin (ie HBIg, VZIg)
       IVIG
       Monoclonal antibody (palivizumab for RSV),
       Antibody of animal/human origin (botulism
        antitoxin)




                  Childhood Vaccination     Feb 15 2007
Ideal Immunizing Agent
   Easy to produce in well-standardized
    preparations
   Quantifiable and stable in potency
   Easy to administer
   Should not produce disease in recipient or
    susceptible contacts
   Should induce long lasting immunity
   Free of contaminating and toxic
    substances
   Only minimal adverse reactions

                Childhood Vaccination    Feb 15 2007
Types of Vaccines

 Live attenuated
 Inactivated or killed viruses

 Recombinant products

 Immunogenic components of
  bacteria
 Toxoids




             Childhood Vaccination   Feb 15 2007
   Vaccine                      Type                     Route
Diphteria-tetatnus                 Toxoid                  IM


Acellular Pertussis   Inactivated bacterial components     IM


Hemophilus type B     Polysaccharide-protein conjugate     IM


 Meningococcal                Polysaccharide               SC
                      Polysaccharide-protein conjugate     IM

  Pneumococcal                Polysaccharide               IM
                      Polysaccharide-protein conjugate

    Poliovirus                Inactivated virus           IM/SC


    Influenza           Inactivated viral components       IM


    Hepatitis A           Inactivated viral antigen        IM

   Hepatitis B           Recombinant viral antigen         IM

      MMR                   Live attenuated virus          SC

     Varicella             Live-attenuated virus           SC

    Rotavirus               Live attenuated virus          PO

   Yellow Fever             Live attenuated virus          SC
    Vaccine            Polysaccharide               Conjugate

   Response          “thymus-dependent”        “thymus independent”
                     Stimulate B-cells only   activates macrophages,
                    Dependent on marginal       T-helper cells and B-
                        zones in spleen                 cells
                                               Independent of spleen
     < 2 yo                   No                       Yes
    Ab Titres          Modest, variable           High, constant
    Duration                Short                      Long
    Memory                    No                       Yes
Decreases carrier             No                       Yes
     state
What is in a vaccine?

   Antigen
       whole organism attenuated
       toxoid (cell free preparation of toxins)
       constituents (e.g: polysaccharide capsule)
       recombinant antigens
   Suspending fluid
   Preservatives, stabilizers, antibiotics
       eg. thimerosal
   Adjuvants (eg. aluminum salts)

                   Childhood Vaccination      Feb 15 2007
Thimerasol and Vaccines
   Mercury containing organic compound
   Used as preservative since 1930’s
   Methyl mercury = neurotoxin
   Removed from or reduced to trace amounts in
    all vaccines routinely recommended for
    children < 6 years
        exception of inactivated influenza vaccine

   “no change in autism rates as a function of amount of
    thimerosal child received in 1st 6 months of life”
                                              • Lancet 2002:


                     Childhood Vaccination            Feb 15 2007
Site and route

   Breastfeeding does not interfere with
    successful immunization with oral vaccine
   IM injection:
       • Newborns/infants 2-12 m: anterolateral thigh
         muscle
       • > 1 y: deltoid +/- anterolateral thigh muscle
       • Adolescents/adults: deltoid
   Avoid buttocks
   SC: at 45 degree angle

                  Childhood Vaccination            Feb 15 2007
How many vaccines are
“routinely” recommended in
Canada?

 Health Canada recommends
  vaccination against 12 vaccine-
  preventable diseases.
 With the combination vaccines, a
  total of 15 shots will be given
  throughout childhood and
  adolescence
            Childhood Vaccination   Feb 15 2007
Current Routine childhood
Vaccines

   DPT (Diphtheria, Pertussis, Tetanus)
    / HIB / Polio
   MMR (Mumps, Measles, Rubella)
   Hepatitis B
   Meningococcus
   Pneumococcus
   Varicella
   Influenza

                Childhood Vaccination      Feb 15 2007
            Routine immunization programs for infants
               and children in Canada, June 2005
                     DaPT/IPV/
Province or                                                    MMR               DaPT/IPV                                                   Meningococcal       Pneumococcal
territory
                        Hib              Hepatitis B
                                                              (2 doses)           (4-6 yrs)
                                                                                                        dTap             Varicella            conjugate           conjugate         Influenza
                    (2, 4, 6, 18 mo)

British
                           √              2, 4, 6 mo          12, 18 mo                √               Grade 9              12 mo              2, 12 mo         2, 4, 6, 18 mo         6-23 mo
Columbia

Alberta                    √               Grade 5          12 mo, 4-6 yrs             √               Grade 9              12 mo             2, 4, 6 mo        2, 4, 6, 18 mo         6-23 mo
Saskatchewan               √               Grade 6            12, 18 mo                √               Grade 8              12 mo               12 mo           2, 4, 6, 18 mo           N/A

Manitoba                   √               Grade 4          12 mo, 4-6 yrs             √               Grade 9              12 mo              Grade 4          2, 4, 6, 18 mo         6-23 mo

                                                                                                                                              12 mo or
                                          Grade 7                                                                                             12 yrs or
Ontario                    √                                  12, 18 mo                √              14-16 yrs             15 mo                               2, 4, 6, 15 mo          ≥6 mo
                                          (2 doses)                                                                                         15-19 yrs and
                                                                                                                                              high risk

Quebec                     √               Grade 4            12, 18 mo                √               Grade 9          N/A ** 12 mo            12 mo           2, 4, 6, 15 mo         6-23 mo

New
                           √              0, 2, 6 mo          12, 18 mo                √               Grade 9              12 mo               12 mo            2, 4, 12 mo           6-23 mo
Brunswick

Nova Scotia                √               Grade 4          12 mo, 4-6 yrs             √              Grade 10              12 mo               12 mo           2, 4, 6, 18 mo         6-23 mo

PEI                        √             2, 4, 15 mo          15, 18 mo                √               Grade 9              12 mo               12 mo           2, 4, 6, 18 mo           N/A

NL                         √               Grade 4            12, 18 mo                √               Grade 9              12 mo               12 mo           2, 4, 6, 18 mo           N/A

Northwest
                           √              0, 1, 6 mo          12, 18 mo                √               Grade 9              12 mo              2, 4 mo               N/A               6-23 mo
Territories
                                         2, 4, 12 mo;
Yukon                                                                                                                                                           2, 4, 6, 12-18
                           √             <19 yrs not          12, 18 mo                √               Grade 9               N/A               2, 6 mo                                 6-23 mo
Territory                                                                                                                                                                 mo
                                         immunized
Nunavut                    √              0, 1, 9 mo          12, 18 mo                √               Grade 9              12 mo                N/A            2, 4, 6, 15 mo          ≥6 mo
DaPT Diptheria-acellular pertussis-tetanus; dTap-diptheria acellular pertussis vaccine; Hib Haemophilus inluenzae type b vaccine; IPV Inactivated polio vaccine; MMR Measles-mumps-rubella vaccine;
      mo Age in months; N/A Not available; NL Newfoundland and Labrador; PEI Prince Edward Island; yrs Age in years
Why do we need to vaccinate
against diseases that don’t
exist anymore?
   Britain, Sweden, and Japan - cut back the
    use of pertussis vaccine because of fear
    about the vaccine.
   Result: epidemic of more than 100,000
    cases of pertussis and 36 deaths by 1978.
   Major epidemic of diphtheria  in former
    Soviet Union, increase from 839 cases in
    1989 to nearly 50,000 cases and 1,700
    deaths in 1994.
   At least 20 imported cases in Europe and
    two cases in U.S. citizens working in the
    former Soviet Union.
                 Childhood Vaccination    Feb 15 2007
Diphtheria
   Caused by toxigenic strains of
    Corynebacterium diphtheriae
   Invasion of respiratory tract, skin,
    conjunctiva
       laryngeal and tracheal infection results in
        airway obstruction
       Exotoxin effects--toxic to heart, kidney and
        peripheral nerves
       DIC, myocarditis, polyneuritis


                  Childhood Vaccination       Feb 15 2007
Diphtheria vaccine -
Toxoid
   Formaldehyde inactivated diphtheria toxin
   Used in Canada since 1930’s
   Titres decline slowly with time but can be
    boosted
   Immunity = antitoxic (not antibacterial)
   Lower and higher potency (d and D)
   Who gets d? D?
       D  < 7 yo
       d  > 7 yo
       Toxoid causes more severe local reaction with
        increasing age.

                  Childhood Vaccination     Feb 15 2007
Immunity (Diphtheria)

 Primary series (DTaP) and boosters
  (Td)
 IM

 85% protection after 4 doses

 Adverse reactions:
     Transient local and febrile rx
     Frequency increasing with age


               Childhood Vaccination   Feb 15 2007
Pertussis

 Bordetella pertussis
 High morbidity and mortality in
  infants
 Vaccine introduced 1942

 Incidence decreased 82% but still
  many cases reported/year



             Childhood Vaccination   Feb 15 2007
Pertussis

   Biphasic illness
       Catarrhal (1-2 wk), paroxysmal
        (weeks) and convalescent stages
 Infants may have apnea,
  pneumonia, encephalopathy
 Epidemics every 3-5 years




                Childhood Vaccination   Feb 15 2007
Pertussis vaccination

 Whole cell vaccine no longer
  available
 Acellular vaccine
     • Pertussis toxoid
 Better efficacy: 85%
 Less frequent local and systemic
  side effects, more effective
 Duration of protection unknown

               Childhood Vaccination   Feb 15 2007
Reported cases of Pertussis in Canada
1985-2004




   Resurgence partly attributable to low
    vaccine efficacy of previously used whole-
    cell vaccine Childhood Vaccination    Feb 15 2007
Tetanus

 Clostridium tetani
 Ubiquitous in soil
 Produces potent neurotoxin
 Acute often fatal neurologic disease
  with severe muscle spasms
       last death in 1995
   Vaccine introduced in 1950’s


                 Childhood Vaccination   Feb 15 2007
Tetanus Vaccine
   Detoxification of tetanus toxoid with formalin
   Combined with aluminum salts
   Protective levels x at least 10 years
   Should not give > q5 yrs
   Tetanus Ig can be used at time of injury if
    not fully immunized
   Allergic reactions rare (arthus reactions)
   Preparations contain either preservatives:
        • Thimerosal
        • 2-phenoxyethanol +/- formaldehyde
                  Childhood Vaccination       Feb 15 2007
Haemophilus Influenzae
Type B
   Haemophilus influenza
   Leading cause of serious invasive
    infections prior to vaccine
   6 capsular types
       Type B = most invasive
   Until 1990: Hib = most common cause of
    meningitis
   Epiglottitis, septic arthritis, pneumonia


                  Childhood Vaccination   Feb 15 2007
HIB vaccine
   1986: capsular polysaccharide vaccine
   1988-90: conjugate vaccines
   1992: 1st infant vaccine became available

   HIB capsular polysaccharide covalently
    linked to carrier protein
       eg. tetanus toxoid, mutant diphtheria toxin,
        OMP of Neiserria meningitidis, diphtheria
        toxin
   98% decrease in cases since vaccine
    introduction
                    Childhood Vaccination       Feb 15 2007
Incidence of Invasive Hib disease
HIB Vaccine
   In Canada, as of 1997, only Hib
    conjugate vaccine licensed for use
   Given as primary series with booster
       Protective antibodies achieved in 99%
        after 3 doses
       Ab then decline  booster at 15-18 mths
   Products interchangeable
   Given as combination vaccine with DPT
    and Polio (Pentacel)
   ** not in quadracel
   Few adverse reactions
                  Childhood Vaccination     Feb 15 2007
Poliovirus
   Enterovirus: 3 serotypes
      1955: Inactivated vaccine (Salk/IPV)
      1959: Last major epidemic in Canada
      1962: Trivalent oral live vaccine (Sabin/OPV)
      1977: Last reported case of indigenously
       acquired wild type poliovirus
      1979: Minor outbreaks in AB, BC, ON from
       imported cases
      1991: Last indigenous case in Peru



   Since 1990: only IPV used in Canada

                   Childhood Vaccination          Feb 15 2007
Polio Vaccines--IPV

   IPV: 3 serotypes
   formalin-inactivated
   Streptomycin, polymyxin B and neomycin
    may be present as preservatives
   Enhanced formulation with higher potency
    and more immunogenic than original
   Primary series will protect >99% of
    recipients
   Few adverse effects

                Childhood Vaccination   Feb 15 2007
Polio Vaccines--OPV
   Live attenuated: 3 serotypes
   Immune response similar to natural
    infection with mucosal IgA immunity
   Vaccine virus shed in stool 1-2 weeks
   Cheap, easy to administer, effective
   Used in outbreak control
   Associated with VAPP (1 case/2.4 million
    doses)


                Childhood Vaccination   Feb 15 2007
Vaccine-associated
Paralytic Poliomyelitis
   Acute paralytic illness in which
    vaccine-like poliovirus is isolated from
    stool samples, and the virus is
    believed to be the cause of the
    disease.
   Mostly from the OPV



                Childhood Vaccination   Feb 15 2007
Mumps

 Paramyxovirus
 Systemic disease with parotitis

 Orchitis, oophoritis, aseptic
  meningitis
 Licensure of vaccine in 1969




             Childhood Vaccination   Feb 15 2007
Reported cases of Mumps,
1990-2004
                                Outbreak in Northern Alberta
                                due to undervaccinated
                                communities (philosophical
                                reasons)




        Childhood Vaccination                      Feb 15 2007
Mumps Vaccine

 Live attenuated vaccine
 Combined with measles and rubella
  vaccines (MMR)
 Antibody develops in (95%)

 Rare adverse events




            Childhood Vaccination   Feb 15 2007
Measles

 Paramyxovirus
 Cough, coryza, conjunctivitis

 Rash and Koplik spots

 Complications include pneumonia,
  encephalitis
 SSPE




            Childhood Vaccination   Feb 15 2007
Measles vaccine

   Live attenuated vaccine
   Vaccine protection 95-99%
   Vaccine sensitive to heat
   Available alone, MR or MMR
   Prepared in chick fibroblast cell
    cultures
   All preparations may contain traces of
    antibiotics (e.g., neomycin) and
    stabilizer such as gelatin.
                 Childhood Vaccination       Feb 15 2007
Side Effects
   Mild, non-transmissible and usually
    subclinical infection.
   Fever +/- rash in 5% to 10% 7-10 days
    after
   Fever may trigger a seizure in susceptible
    children
   Risk is low, benefit >> potential risk
    associated with febrile seizures
   Transient thrombocytopenia occurs,
    rarely, during the month after
    immunization

                 Childhood Vaccination    Feb 15 2007
My child is allergic to eggs,
she can’t have the MMR!!
   Egg allergy should no longer be
    considered a contraindication to
    immunization with MMR.
   Administer in the routine manner without
    prior skin testing.
   Should take place where adequate
    facilities are available to manage
    anaphylaxis.
   Those at risk should be observed for 30
    minutes after immunization for any sign of
    allergic reaction.

                 Childhood Vaccination    Feb 15 2007
My nephew got autism
from the MMR!




       Childhood Vaccination   Feb 15 2007
MMR and Autism

 Wakefield studies of GI disease in
  autism
 Have not been replicated

 No epidemiologic evidence in many
  large studies that MMR vaccine
  associated with autistic spectrum
  disorders or IBD
                        • Lancet. Vol 351. Feb 28, 1998


            Childhood Vaccination               Feb 15 2007
   “there is no association between
    autism and MMR vaccine or
    vaccines that contain thimerosal as a
    preservative”
       AAP, Institute of Medicine




                 Childhood Vaccination   Feb 15 2007
Rubella

 Togavirus
 Mild disease: rash, arthralgias, fever

 Intrauterine infection:
       Congenital Rubella Syndrome
        cardiac lesion, eye defects, deafness
        etc
   last epidemic in NA in 1964

                 Childhood Vaccination   Feb 15 2007
Rubella Vaccine

 Live attenuated virus
 induces antibody in 95% , lifelong (?)

 side effects: rash, lymphadenopathy,
  mild joint pain
 Do NOT give to pregnant woman




             Childhood Vaccination   Feb 15 2007
Varicella

 Varicella Zoster Virus
 Generalized vesicular rash, fever

 Complications:
     Bacterial superinfection (esp. GAS)
     Necrotizing fasciitis
     Acute cerebellar ataxia
     Encephalitis


               Childhood Vaccination   Feb 15 2007
Varicella
   More severe disease in
     Adolescents, adults and newborns
     Immunocompromised
     Reyes Syndrome
     Fetal infection with embryopathy

   Establishes latency in dorsal root
    ganglia, reactivates as zoster
    (shingles)

               Childhood Vaccination   Feb 15 2007
Varicella Vaccine
   Live attenuated Oka strain
   Licensed in the US in 1995 & Canada
    in1999
   Immunogenicity:
        • 95% of children develop antibody after 1 dose
        • 78-82% of those >13 yr. develop antibody after
          1 dose and 99% after 2 doses
   give after 1 year of age



                   Childhood Vaccination           Feb 15 2007
Varicella Vaccine
   70 – 90 % effective in preventing mild to mod disease
   > 95% effective for prevention of severe disease
   Varicella transmission from vaccine recipients with mild
    breakthrough disease has been documented
   Reactions
        pain and erythema at injection site (20%)
        vesicular rash (3-5%) 3 weeks after immunization
          • Not necessarily due to vaccine, could be wild-type infection
   Age-specific risk of zoster appears to be lower in those
    immunized
   Vaccine-associated virus transmission to contacts is
    rare
   Risk of transmission only if a rash develops on the
    immunized person

                        Childhood Vaccination                    Feb 15 2007
Varicella Vaccine--
Recommendations
 Age 12 mo - 12 yr: 1 dose
 > 12 yr: 2 doses (4-8 weeks apart)
 Adults: encouraged
     Priority for workers in health care,
      child care institutional care, college
      students, military
     Non-pregnant women of
      childbearing age
     International travelers

                Childhood Vaccination    Feb 15 2007
Varicella Vaccine--
Considerations and
Contraindications
   Immunocompromised Patients
       However OK for:
         • ALL-remission for 1 yr
         • HIV-CD4+ > 25% (CDC class 1)
       children receiving steroids
       households with potential contact with
        immunocompromised persons (rash)
   Pregnancy  unknown effects on fetus
   Salicylates

                   Childhood Vaccination         Feb 15 2007
My son just got his MMR only. When
can he receive the Varicella vaccine
and Pneumococcal vaccine?
   Minimum of 4 wks between 2 live
    attenuated virus vaccine
   Other vaccines can be given
    simultaneously or at any time after
   It is thought that a parenterally-
    administered live vaccine can interfere
    with replication of a second live vaccine
    administered after it.


                 Childhood Vaccination     Feb 15 2007
Influenza

   Orthomyxovirus- 3 types: A, B, C
   2 surface antigens
       Hemagglutinin (H1, H2, H3,)
       Neuraminidase (N1, N2)
   H5N1 so far is primarily an avian strain
   Antigenic drifts (minor seasonal variations)
    and shifts (major, and only with A  risk
    of pandemics)
   Fever, myalgias, HA, cough
                  Childhood Vaccination    Feb 15 2007
Naming the Influenza Virus




         Childhood Vaccination   Feb 15 2007
Could this be 6C2?
Influenza Vaccine
   Inactivated, produced in embryonated hen
    eggs
   contains 3 strains (2 A’s, 1 B)
   must re-vaccinate every year
   1-2 strains are changed qyear in
    anticipation of the predominant influenza
    strains
   children < 9yr. require 2 doses (if not
    previously vaccinated)


                Childhood Vaccination   Feb 15 2007
Influenza Vaccine

 50-90% efficacy
 duration of protection < 1 yr.

 Cold adapted, live attenuated
  vaccine for intranasal admin.
  available
 cannot use < 6 months of age




             Childhood Vaccination   Feb 15 2007
Influenza Vaccine--Who should
get it?
   Healthy children 6-24 months + household
    contacts
   Priority to high risk:
       Chronic lung conditions
       Heart disease
       HIV
       Hemoglobinopathies (SS)
       ASA therapy
       Renal dysfunction
       Chronic metabolic disease (DM)
       Immunosuppressive disorders
                  Childhood Vaccination   Feb 15 2007
Influenza Vaccine--Who
should get it?
 Pregnancy: safe at any stage
 Close contacts of high risk patients
       health care workers, family contacts
        of high risk children or adults, home
        care providers to children and
        adolescents in high risk groups



                 Childhood Vaccination   Feb 15 2007
•   3 vaccines are licensed for use in Canada, two produced by Aventis
    Pasteur (Fluzone® and Vaxigrip®) and one by Shire Biologics (Fluviral
    S/F®).
•   All three licensed vaccines use thimerosal (0.01%) as a preservative.
    Gelatin (0.05%) is used as a stabilizer in Fluzone®. Vaxigrip® may contain
    undetectable traces of neomycin, used during production.
Influenza Vaccine--adverse
effects
 Fever, local reactions
 Guillain-Barre Syndrome (1/million)

 Allergic reaction in those with severe
  anaphylactic reaction to chickens or
  eggs




             Childhood Vaccination   Feb 15 2007
Influenza Vaccine
Contraindications
People   who have a severe allergy to chicken eggs.
People  who have had a severe reaction to an influenza
vaccination in the past.
Peoplewho developed Guillain-Barré syndrome within 6
weeks of getting an influenza vaccine previously.
Not   approved for use in children less than 6 months old.
People who have a moderate or severe illness with a
fever should wait to get vaccinated until their symptoms
lessen.




                    Childhood Vaccination           Feb 15 2007
Live Attenuated Influenza
Vaccine (LAIV)


 •Administered intranasally
 •Contains live viruses that can replicate and be
 shed
 •Approved for healthy adults under age 50 and
 children 5 or older (in US not Canada)
 •Immune response depends on susceptibility of
 the host at the time of immunization.
 •More costly than TIV
               Childhood Vaccination       Feb 15 2007
Common Side Effects: LAIV
  Children                           Adults

  runny   nose                       runny   nose
  headache                           headache

  vomiting                           sore   throat
  muscle   aches                     cough

  fever




              Childhood Vaccination                    Feb 15 2007
Live Attenuated Influenza Vaccine:
Additional Contraindications

  Immunosuppressed              hosts
  Children and adolescents receiving
  chronic aspirin therapy—these individuals
  may receive inactivated vaccine
  Not licensed for use in pregnancy and in
  persons with underlying medical
  conditions i.e. chronic heart/lung disease




               Childhood Vaccination       Feb 15 2007
Streptococcus
pneumoniae
 Gram positive diplococci
 90 serotypes

 Most invasive disease caused by 4,
  6B, 9V, 14, 18C, 19F, 23F
 OM, bacteremia, meningitis,
  pneumonia
 Increasing resistance to Penicillin


             Childhood Vaccination   Feb 15 2007
Pneumococcal Vaccines
   23-valent polysaccharide vaccine
       not effective in children < 2yr.
       Available since 1983
   7 serotype protein conjugate vaccine
       immunogenic in infants
       efficacious in preventing meningitis,
        bacteremia, pneumonia, OM caused by
        serotypes present in the vaccine



                    Childhood Vaccination   Feb 15 2007
Pneumococcal Vaccines--who
should get them

   All children 2-23 months
   24-59 months at increased risk of invasive
    disease:
       Hb SS
       Functional or anatomic asplenia
       Nephrotic syndrome or CRF
       Transplantation, chemo, steroids
       HIV
       CSF leaks

                  Childhood Vaccination    Feb 15 2007
Give concurrently with other childhood vaccines at
             2, 4, 6, 12-15 months
Meningococcal Infections

 Neisseria meningitidis
 Gram negative diplococcus

 13 serogroups, A, B, C, Y, W-135
  most common in systemic disease
 C: most virulent

 A: endemic in sub-Saharan Africa

 Meningococcemia, meningitis


            Childhood Vaccination   Feb 15 2007
Meningococcal Vaccines

   Polysaccharide vaccine
       A,C,Y,W-135 for children age >2
   Protein Conjugate Vaccine
     contains C only
     for use at 2, 4, 6, 12-15 months
      (funding differs for each province)
   Quadrivalent Conjugate Vaccine
       A, C, Y, W-135 licensed for 11-55 y

                 Childhood Vaccination   Feb 15 2007
Meningococcal Vaccines--Who
should get them

 All children
 functional or anatomic asplenia

 Terminal complement component
  deficiency
 Travelers

 Transplantation patients

 Used in epidemics


            Childhood Vaccination   Feb 15 2007
Vaccines for Travelers

 Hepatitis A
 Yellow Fever

 Typhoid

 Cholera

 Japanese encephalitis

 Rabies




            Childhood Vaccination   Feb 15 2007
Hepatitis B

   DNA virus
   3 major antigens:
       surface (HBsAg), (HBeAg)
       core (HBcAg)
   HBeAg is associated with viral
    replication and high infectivity




                 Childhood Vaccination   Feb 15 2007
Hepatitis B

   HBV infection after blood or body fluid
    exposure (needle-stick, sexual,
    perinatal)
   Initial infection may be:
        • asymptomatic (50%)
        • Symptomatic
        • Fulminant.
   Chronic carrier risk varies with age:
        • infants: 90-95%
        • children <5: 25-50%
        • adults : 6-10%
                   Childhood Vaccination    Feb 15 2007
Hepatitis B



   Highly endemic in Southeast Asia,
    China, eastern Europe, Africa, Central
    Asian Republics, Amazon basin
   Worldwide HBV is a major cause of
    chronic liver disease and primary
    hepatocellular carcinoma

                Childhood Vaccination    Feb 15 2007
Hepatitis B
   High risk groups:
       IVDU
       Multiple sexual partners
       Occupational exposure (institutions,
        hospitals)
       Hemodialysis patients
       Household or sexual contacts of person
        with acute or chronic infection
       Patients with clotting disorders receiving
        blood products

                   Childhood Vaccination       Feb 15 2007
Hepatitis B Vaccine

 Contains purified HBsAg
 Recombinant vaccines available
  produced from genetically
  engineered yeast strain
 Minimal side effects

 Need 3 doses at 1, 2 and 6 months

 90-95% efficacious


            Childhood Vaccination   Feb 15 2007
Hepatitis B Vaccine

 Nonresponders (Anti-HBsAg > 10
  IU) need to be re-immunized
 Universal immunization for children
  (infants or pre-adolescents)
 Grade 4 in Quebec




             Childhood Vaccination   Feb 15 2007
I heard that the hepatitis B
vaccine causes multiple
sclerosis!
   Association between hep B vaccination
    and MS in a case-control study.
   192 women with MS and 645 controls
   RR hep B vaccination at any time before
    onset of MS and within 2 yrs of onset was
    0.9 and 0.7 respectively.
   The authors concluded that there was no
    association between hepatitis B
    vaccination and MS.
                                • Ascherio and colleagues, 2001


                Childhood Vaccination                   Feb 15 2007
Hepatitis A

 RNA virus
 Fecal-oral spread

 Food and water-borne outbreaks,
  international travel, MSM, injection
  drug use, child care center and
  family contacts
 Fever, jaundice, nausea

 Fulminant disease rare
             Childhood Vaccination   Feb 15 2007
Hepatitis A Vaccine

 2 inactivated vaccines available
 use > 1 yr of age x 2 doses

 pediatric and adult formulations

 seroconversion after 1 dose 95-99%

 100% after second dose

 ? Long term efficacy




            Childhood Vaccination   Feb 15 2007
Hepatitis A Vaccine--Who
should get it

 foreign travel
 children living in communities with
  elevated Hepatitis A rates
 chronic liver disease

 homosexual and bisexual men

 IVDU

 clotting disorder

 occupational exposure risk
             Childhood Vaccination   Feb 15 2007
Hepatitis A Vaccine--Who
should get it

   Other Considerations
     Child care staff and attendees
     Custodial care institutions
     Hospital personnel
     Food handlers




               Childhood Vaccination   Feb 15 2007
Rabies

 RNA virus, Rhabdovirus family
 Acute illness with progressive CNS
  disease
 Almost uniformly fatal

 Bats, skunks, raccoons, foxes

 consider dogs, cats, ferrets




            Childhood Vaccination   Feb 15 2007
Rabies Vaccine

 Human diploid cell vaccine
 Post-exposure prophylaxis
       give IM Day 1, 3, 7, 14 and 28
   Pre-exposure vaccination
       give intradermal day 0, 7, 21 or 28.




                 Childhood Vaccination   Feb 15 2007
Rabies Vaccine--Adverse
Effects

   HDCV: local reaction 15-25%
     HA, nausea, abd. Pain 10-20%
     Immune Complex reactions with
      booster doses
   Nerve Tissue Vaccines: available in
    many parts of the world
       neuroparalytic reactions in 1:2000-
        1:8000
                 Childhood Vaccination   Feb 15 2007
Rabies Vaccine--Who
should get it
 Vets and animal handlers
 Certain lab workers

 Persons traveling to live in areas
  where canine rabies is common
 Spelunkers




             Childhood Vaccination     Feb 15 2007
               BCG vaccine
• Live-bacteria vaccine prepared from
  attenuated strains of M. bovis
• Recommended for administration at birth
  in > 100 countries
• Used to prevent
  disseminated manifestations
  of TB, but does not prevent
  infection with M. tuberculosis
BCG Vaccine

 Efficacy: 80% protective efficacy
  against meningeal and miliary TB in
  children
 Difficult to say what efficacy is
  against pulmonary TB




             Childhood Vaccination   Feb 15 2007
BCG: adverse reactions

 1-2% local adverse reaction
  (subcutaneous abscess, regional
  lymphadenopathy)
 Rarely osteitis

 Disseminated fatal infection with
  severe immunocompromised people



            Childhood Vaccination   Feb 15 2007
Dealing with vaccine
refusal
   Ultimately, parents / patients have the
    right to decide
   Always use a non-judgmental approach
   What are their concerns, health beliefs,
    experiences?
   Make sure they understand the real risks
    posed by vaccine-preventable diseases
   Offer valid sources of information


                Childhood Vaccination    Feb 15 2007
Coming soon to a primary
care provider near you….
 HPV – licensed
 MMR-V

 Rotavirus – licensed

 Quadrivalent conjugated
  meningococcal (A, C, Y, W135) –
  licensed



            Childhood Vaccination   Feb 15 2007
Conclusions

 Active and Passive immunization
 Live attenuated and killed vaccines

 Impact on large populations

 Potential for eradication of disease

 Future development crucial to
  control emerging infections


             Childhood Vaccination   Feb 15 2007
Resources

   www.cdc.gov/nip/publications/VIS/default.htm
   www.immunize.org
   www.cps.ca/english/publications/InfectiousDiseas
    es.htm (Canadian Pediatric Society)
   http://aapredbook.aappublications.org/ (American
    Academy of Pediatrics)
   http://www.phac-aspc.gc.ca/im/index.html
    (Canada public health)
   www.inspq.qc.ca/ (Quebec public health)


                  Childhood Vaccination        Feb 15 2007

				
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