UPDATE ON IMMUNIZATIONS
From Mayo Clinic Pediatric Days, presented September 8-9, 2005, sponsored by the Mayo Clinic College of Medicine
Robert M. Jacobson, MD, Chair and Professor, Department of Pediatrics, Mayo Clinic, Rochester, Minnesota
| Meningococcal disease: bacterial infection caused by Neisseria meningitidis; manifests as meningococcemia and meningitis;
10- to 15-yr cycle; initially presents as benign viral illness; however, progresses rapidly and can kill within hours; clinical
sequelae—10% to 14% of patients die despite appropriate antibiotic treatment (40% of patients who develop
meningococcemia); 11% to 19% who survive left with permanent disabilities
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| Meningococcal strains and incidence: 5 serogroups of N meningitidis of concern (A, B, C, W135, and Y; no vaccine
available against B, which accounts for 45% of meningococcal disease); highest rate of disease in infants; second peak in
adolescence and young adulthood
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| Risk factors for teenagers: crowded living conditions or social situations; smoking or exposure to environmental smoke;
sharing drinks, glasses, and water bottles; kissing
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| Previous recommendations: in 2000, Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization
Practices (ACIP) recommended matriculating college students be informed of risk for meningococcal disease
and offered meningococcal polysaccharide vaccine (MPSV-4); studies show risk for disease elevated in freshmen living
in dormitories
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| Vaccine: previous—MPSV-4 (Menomune); quadrivalent (targets serogroups A, C, W135, and Y; no protection against
B); no adjuvant; new vaccine licensed by Food and Drug Administration (FDA) in 2005—meningococcal conjugate
vaccine (MCV-4; Menactra); quadrivalent; conjugated to diphtheria toxoid; no adjuvant
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| Conjugation: advantages—T cell-dependent immune response; immune memory; lack of hyporesponsiveness; booster effect;
long-term protection; reduction in carriage; herd immunity; efficacy—use of Haemophilus influenzae B (Hib) conjugate
vaccine has reduced incidence of Hib meningitis from 20,000 to 300 cases annually; immunogenicity—MCV-4
appears to do better job in providing antibody protection; MCV-4 and MPSV-4 highly immunogenic (seroconversion rate
98%-100%), difference in duration (≥8 yr vs 3-5 yr)
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| Adverse events: compared with MPSV-4, MCV-4 has same rate of serious adverse events (1.3% at 6-mo follow-up); most
common reactions headache, fever, and pain at injection site
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| Concomitant administration: MCV-4 studied with tetanus toxoid and diphtheria vaccine (Td) and with typhoid V1
polysaccharide vaccine; in both settings, concomitant administration showed no interference with either vaccine and no
increase in adverse effects
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| Fear of revaccination: with unconjugated meningococcal C vaccine, found that revaccination led to hyporesponsiveness
(immune tolerance); led to recommendation that vaccine be given only once; studies with conjugated vaccine show much
better results
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| Recommendations: MCV-4 licensed for patients 11 to 55 yr of age; should be given—routinely at 11 to 12 yr of age
(along with Td); in next 2 to 3 yr, as catch-up in patients entering high school (15-16 yr of age); in next 5 to 6 yr, to finish
college matriculation drive; recommended not just for freshmen residing in dorms, but for other college attendees seeking
protection, and for anyone seeking additional protection against meningococcal disease; patients vaccinated with MPSV-
4 should wait 5 yr before receiving MCV-4; MCV-4 vaccine of choice for patients 11 to 55 yr of age (MPVS-4 can be
used if MCV-4 not available); MPVS-4 preferred for patients <11 yr of age and >55 yr of age
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| Contraindications: demonstrated hypersensitivity to components; previous life-threatening reaction
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| Pertussis (whooping cough): Bordetella pertussis causes highly communicable respiratory illness with serious consequences
for infants <1 yr of age (can be fatal); causes spells of coughing, choking, dyspnea, and apnea that can last for
weeks to months; potentially serious in adolescents and adults (more typically causes prolonged [“100-day”] cough, often
without choking, dyspnea, or apnea; can result in missed days of school and work; also makes these patients contagious
vectors for infants too young to receive full 3-dose course of vaccination); treatment effective if given early; however,
preventive antibiotics given only if there is known exposure; disease relatively subtle and hard to diagnose early
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| Rates of pertussis cases: 90% reduction in pertussis in infants after introduction of diphtheria, tetanus, and pertussis vaccine
(DTP) in 1940s; 66% of cases in adolescents and adults (remainder in infants <6 mo of age who have not been fully vaccinated;
fairly rare among vaccinated children 6 mo to 10 yr of age)
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| Vaccines: previous—not licensed for adolescents and adults; reactivity prevented use; new—in 2005, FDA licensed 2
new tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccines, Boostrix (manufactured by GlaxoSmithKline)
and Adacel (manufactured by Sanofi Pasteur); Boostrix licensed for patients 10 to 18 yr of age, Adacel for patients
11 to 64 yr of age
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| Boostrix: components same as in diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine Infanrix, but in
lesser amounts; all adsorbed on aluminum hydroxide; no preservative, no thimerosal; immunogenicity—for pertussis,
not inferior to 3-dose Infanrix series; for tetanus and diphtheria, at least as good as licensed Td vaccine for adolescents;
reactivity—local pain more common than with Td vaccine; also can cause transient headaches, fever, and fatigue; injection
site reactions
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| Adacel: components same as in DTaP vaccine Daptacel, with 2 exceptions (lesser amounts of diphtheria toxoid and detoxified
pertussis toxin); adsorbed on aluminum phosphate; no thimerosal or mercury-containing preservative;
immunogenicity—for pertussis, compared well to 3-dose series of Daptacel; for diphtheria and tetanus, same as Td vaccine;
reactivity—compared to licensed Td vaccine, serious adverse event rates roughly equivalent; adolescents slightly
more reactive; adult reactivity same as with Td vaccine
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| Contraindications: hypersensitivity to any component; previous serious allergic reaction; encephalopathy within 7 days
of receiving pertussis vaccine; progressive neurologic disease; warnings and precautions for infant DTaP vaccine also apply
to new Tdap vaccines
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| ACIP recommendations: patients 11 to 12 yr of age should routinely get Tdap instead of Td vaccine; patients 13 to 18 yr
of age should get Tdap if not yet given Td vaccine; encourage—patients 11 to 18 yr of age who got Td vaccine to get
Tdap (5 yr after Td if not in midst of pertussis epidemic; initial recommendations stated that, in local pertussis epidemic,
patients should get Tdap 6 mo after last dose of Td; however, speaker believes CDC will be coming out with new recommendation
indicating that Tdap can be given any time after Td vaccine); no decision—for adults (family; close contacts,
day care workers; health care workers; coaches; teachers)
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| Influenza: responsible for 36,000 deaths per year in United States; rates of serious illness and death highest in individuals
≥65 yr of age or <2 yr of age (also higher in those with certain medical conditions); vaccine remains primary method to
reduce illness; benefits of vaccination clear
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| ACIP influenza recommendations: those at increased risk for complications from flu should receive yearly vaccination
(includes those ≥65 yr of age; children 6-23 mo of age; pregnant women; those with certain chronic medical conditions);
also recommended for persons 50 to 64 yr of age with elevated risk for various conditions and for those living with or
caring for individuals at high risk
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| New recommendations for 2005: include all patients with compromised respiratory function; all health care workers;
plan on using inactivated and live attenuated intranasal vaccine (special encouragement for using live attenuated vaccine
in patients healthy enough to receive it when supply of inactivated vaccine is short)
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| Thimerosal: major aspects of complaint against thimerosal—claim that government and industry colluded to suppress
information; accusations that Vaccine Safety Datalink survey run poorly; basis of complaint—mercury constituent of
thimerosal; mercury known neurologic toxin
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| History: thimerosal used since 1930s to prevent infections; widely used in biologics and drugs; FDA began working with manufacturers
in 1999 to systematically remove thimerosal from products (agreed to reduce or eliminate thimerosal exposure)
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| Mercury in thimerosal: ethyl mercury, not methyl mercury; while methyl mercury known neurotoxin, neurotoxicity of
ethyl mercury not well documented; studies of infants found that blood levels of mercury did not exceed limits established
by FDA or Environmental Protection Agency (EPA); appears ethyl mercury cleared by body more quickly than methyl mercury
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| Institute of Medicine (IOM) studies: 2001 report—examined all neurodevelopmental concerns about thimerosal and
mercury; findings (no evidence to accept or reject claims; theoretic concerns exist; prudent to remove); 2004 report—
findings about autism (body of evidence now sufficient to reject causal association with thimerosal)
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| Vaccine Safety Datalink: survey examining effects of thimerosal; published in Pediatrics in 2003; complaints against
study based on fact that initial draft (indicated concern) differed from published report (found no association of neurologic
harm with thimerosal); CDC cites 3 reasons why revisions made from first to third draft of report (errors found in
dataset and in analysis; misinterpretation of low-exposure groups; inclusion of longer period of follow-up)
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| IOM report on thimerosal: majority of studies show no association of thimerosal with autism or neurologic harm
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| Thimerosal today: removed or left in trace elements in all infant vaccines (with exception of some inactivated flu vaccines);
some brands of Td vaccine for older children contain thimerosal, but this will be replaced with Tdap vaccines
(Boostrix and Adacel), which do not contain thimerosal; MCV-4 (Menactra) also without thimerosal
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| Recommendations for managing teenagers needing tetanus boosters diagnosed 1 yr earlier with pertussis and
treated within first week of illness: expect to see recommendation to wait 5 to 10 yr, then give Tdap vaccine
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| Current thought about live attenuated flu vaccine and risk for contagion (ie, whether it can be given to health
care workers): increasing evidence that no risk for contagion; with rare exception of person working in unit with severely
compromised patients, healthy individual should be able to get live attenuated vaccine
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| Can speaker recommend written materials to give parents who refuse to immunize their children (informing
them of consequences): in these situations, speaker first reminds parents they are in his office to receive his advice; secondly,
informs them of what he does with his own children; thirdly, directs them to website www.cdc.gov/nip; another
excellent source offering stories on consequences of not vaccinating children is www.immunize.org
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| Can speaker explain why if parent brings 11-yr-old, 13-yr-old, and 16-yr-old in for well-child check, clinician
should give meningococcal vaccine to 11-yr-old, but not to the other two: speaker would argue that, at 11-yr-old,
15-yr-old, and 17-yr-old well-child visits, clinician should make point of offering vaccination; but if parent of 13-yr-old
asks for vaccination, should go ahead and give it; does ask that clinicians be careful not to routinely offer vaccine at every
visit to all ages
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| But will older children get more benefit than younger children from vaccine? not necessarily; would argue that better
to give it to 11-yr-old than wait and give it to patient when 18 yr of age; if speaker could only vaccinate one age group,
would probably be 11-yr-olds
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| Has study been done on concomitant administration of MCV-4 and Tdap to make sure they are compatible? no;
imagines studies will be under way, but not required for licensure; with Tdap, all one has is general knowledge that inactivated
vaccines usually can be given easily together
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| Would speaker give them 1 mo apart to be safe? no, would give them simultaneously
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| Not seeing pertussis just in children ≥10 yr of age, but in fair number <5 yr of age; is explanation that vaccine
waning even at 4 yr of age? more likely explanation that vaccine not that effective when patients got it; even after 3
doses, success rate of pertussis vaccine in immunizing children only 67%; thinks that by vaccinating larger population
might be able to offer better protection (through herd immunity effect)
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| If clinician treating patient with meningococcal meningitis and has already given himself MCV-4 vaccine, would
he also need prophylaxis? if vaccine has been on board >1 mo, would not need prophylaxis
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| With regard to whole-cell and acellular pertussis vaccines and waning immunity, some opinion that increase in
cases of pertussis due to waning of whole-cell vaccine; that will not see this problem with acellular pertussis
vaccine; and thus may be giving extra vaccine for no reason: entering age where caring for many pertussis patients
who have only received acellular vaccine; true that some studies in Europe indicate that acellular vaccine will be more effective
than whole-cell version; however, even in best of circumstances, evidence does not show vaccine (acellular as
well as whole-cell) has duration longer than 5 to 10 yr
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| Status of second dose of varicella virus vaccine (Varivax): FDA just licensed new combination measles, mumps, rubella,
and varicella (MMRV) vaccine for patients 12 mo to 12 yr of age; ACIP divided on whether sufficient data to support giving
second dose of varicella vaccine at 4 to 6 yr of age, but some indication that those against second dose might change mind if
there was combination vaccine
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| Case scenario of mother showing up at office belatedly to have child vaccinated for pertussis; child already has
disease; how should clinician proceed: 1991 ACIP recommendation is to give DT vaccine; however, speaker believes no
real harm (and easier for clinician and family) to give child DTap vaccine
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| What is status of vaccines for severe acute respiratory syndrome (SARS) and avian flu: conducting clinical studies
with human test subjects being given versions of both vaccines
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Educational Objectives
| The goal of this activity is to provide listeners with an update on immunization, focusing on meningococcal disease, pertussis,
and influenza, and the claims against thimerosal and its use in vaccines. After hearing and assimilating this program, the
clinician will be better able to:
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 | 1. Cite the current incidence of meningococcal disease, pertussis, and influenza, some of the potential sequelae of these
conditions, and the population groups at greatest risk.
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| 2. Discuss the new meningococcal conjugate vaccine recently licensed by the Food and Drug Administration (FDA),
name some of the advantages of conjugation, and consider use of the new vaccine as recommended by the Centers
for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP).
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| 3. Describe the tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccines recently licensed for adolescent
and adult use and apply them to pertussis immunization according to the most recent ACIP recommendations.
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| 4. Recognize those patient populations requiring annual influenza immunization (per ACIP recommendations) and
consider (and adopt) strategies for improving vaccination levels.
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| 5. Understand the complaints against and concerns about the use of thimerosal in vaccines and discuss whether clinical
evidence has found these claims to be warranted.
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Discussed on This Program
Acetaminophen (N -acetyl-P -aminophenol; APAP) [many formulations and trade names]
Diphtheria and tetanus toxoids, combined (DT; Td)
Diphtheria and tetanus toxoids and acellular pertussis vaccine, adsorbed (DTaP) [Daptacel, Infanrix, Tripedia]
Ibuprofen [many formulations and trade names]
Meningococcal polysaccharide vaccine [Menomune-A/C/Y/W-135, Menactra]
7-valent conjugate vaccine Diphtheria and tetanus toxoids, combined (DT; Td)
Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, adsorbed (Tdap) [Boostrix, Adacel]
Thimerosal (49% mercury) [Aeroaid, Mersol]
Varicella virus vaccine [Varivax]
Suggested Reading
Bigham M, Copes R: Thiomersal in vaccines: balancing the risk of adverse effects with the risk of vaccine-preventable
disease. Drug Saf 28:89, 2005; Bilukha OO, Rosenstein N: National Center for Infectious Diseases, Centers for Disease
Control and Prevention (CDC). Prevention and control of meningococcal disease. Recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR Recomm Rep 54:1, 2005; Bridges CB et al: Advisory Committee on
Immunization Practices. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep 49:1, 2000; Caro J et al: Pertussis in adolescents and adults: should we accept
the results? Pediatrics 116:1263, 2005; Casey JR, Pichichero ME: Acellular pertussis vaccine safety and efficacy in
children, adolescents and adults. Drugs 65:1367, 2005; Harper SA et al: Advisory Committee on Immunization Practices
(ACIP), Centers for Disease Control and Prevention (CDC). Prevention and control of influenza. Recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 54:1, 2005; Hayney MS: Vaccine safety:
no link between thimerosal and autism. J Am Pharm Assoc 44:725, 2004; Jacobson RM: Vaccine safety. Immunol Allergy
Clin North Am 23:589, 2003; Jacobson RM, Poland GA: The pneumococcal conjugate vaccine. Minerva Pediatr
54:295, 2002; Jacobson RM, Zabel KS, Poland GA: The overall safety profile of currently available vaccines directed
against infectious diseases. Expert Opin Drug Saf 2:215, 2003; Keyserling H et al: Safety, immunogenicity, and immune
memory of a novel meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine
(MCV-4) in healthy adolescents. Arch Pediatr Adolesc Med 159:907, 2005; Kimmel SR: Prevention of meningococcal
disease. Am Fam Physician 72:2049, 2005; Lee-Wong M et al: A generalized reaction to thimerosal from an influenza
vaccine. Ann Allergy Asthma Immunol 94:90, 2005; McMahon WM: Review: vaccines containing thimerosal are not associated
with autistic spectrum disorders in children. Evid Based Ment Health 8:23, 2005; Meadows M: IOM report: no
link between vaccines and autism. FDA Consum 38:18, 2004; Parker S et al: Thimerosal-containing vaccines and autistic
spectrum disorder: a critical review of published original data. Pediatrics 115:200, 2005; Pichichero ME et al: Combined
tetanus, diphtheria, and 5-component pertussis vaccine for use in adolescents and adults. JAMA 293:3003, 2005; Poland
GA, Tosh P, Jacobson RM: Requiring influenza vaccination for health care workers: seven truths we must accept. Vaccine
23:2251; 2005; Wheeler JG, Simmons AL: Pertussis update. Pediatr Infect Dis J 24:829, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Jacobson has received funding from the Chiron Corporation.
Dr. Jacobson was recorded at Mayo Clinic Pediatric Days, held September 8-9, 2005, in Chicago and sponsored by
the Mayo Clinic College of Medicine. The Audio-Digest Foundation thanks Dr. Jacobson and the Mayo Clinic for
their cooperation in the production of this program.
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