SHINGLES PREVENTION/ELDERLY VACCINATION
| MANAGING AND PREVENTING HERPES ZOSTER AND POSTHERPETIC NEURALGIA —Michael N.
Oxman, MD, Professor of Medicine and Pathology, University of California, San Diego, School of Medicine,
and Staff Physician (Infectious Diseases), Veterans Affairs San Diego Healthcare System, San Diego, CA
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| Definition of herpes zoster (HZ; shingles): painful disease of sensory ganglion, peripheral nerve, and skin
caused by reactivation of varicella-zoster virus (VZV); virus remains latent in dorsal root ganglia after episode
of varicella (chickenpox); HZ usually begins with pain as VZV multiplies, damaging cells and causing necrosis;
within days, vesicular rash similar to chickenpox appears, confined to area on side of body innervated by
nerves from ganglia with reactivated VZV; rash stops at front midline, continuing around to midline in back
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| Postherpetic neuralgia (PHN): major complication of HZ; characterized by neuropathic pain in affected dermatome;
pain persists after rash heals; clinically significant PHN—pain severe enough to adversely affect activities
of daily living (ADLs) or quality of life, and persisting for >3 mo; correlates with pain score of ≥3 on
scale of 0 to 10; relation to age—uncommon in patients <50 yr of age; occurs >50% of time in patients >70 yr
of age; common source of neuropathic pain—second only to diabetic neuropathy
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| Need for vaccine: >1 million new cases annually in United States, >50% in people ≥60 yr of age; no available
treatment for PHN; antiviral therapy shortens duration of rash and reduces early pain, but does not prevent
PHN; corticosteroids ineffective against PHN (toxicity and side effects limit use); pain medications—of limited
value; difficult to use in elderly
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| Antiviral therapy: use of prodrugs famciclovir and valacyclovir mandatory (well-absorbed but expensive);
acyclovir inexpensive but of limited efficacy (VZV >10 times less sensitive to acyclovir than is herpes simplex
virus); bioavailability of acyclovir low and variable
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| Pain management: aggressive treatment of acute pain essential; persistent acute pain may increase probability
of chronic pain (PHN)
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| Limitations of current therapy: pain medications difficult to take and increase risk for falls; topical capsaicin
itself causes pain
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| Theoretic basis for vaccine: British physician R. Edgar Hope-Simpson published paper in 1965 based on 16-
yr observation of patients with shingles and chickenpox; risk for shingles and its severity rises with age as
level of immunity to virus declines; virus reactivates when immunity falls enough and causes shingles, boosting
immunity enough to protect against another outbreak
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| Shingles Prevention Study: randomized double-blind placebo-controlled trial to determine whether boosting
immunity in older people would protect against HZ and PHN; attenuated strain of VZV (Oka) licensed to
Merck; higher levels of VZV required for HZ vaccine than for chickenpox vaccine; study enrolled and actively
followed 38546 participants ≥60 yr of age in 22 centers across United States; combination of automated
telephone response system and personal attention enabled following >95% of participants to end of study
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 | Measuring pain: severity of illness score—HZ–specific pain score; based on severity of pain over time; captures
pruritus and allodynia (pain caused by sensation not normally causing pain, eg, wind blowing on forehead);
patients rated pain on scale of 0 to 10
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| Primary end point: burden of illness due to HZ; based on sum of severity of illness scores for all cases in vaccine
and placebo groups
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| Secondary end point: incidence of clinically significant PHN; score ≥3 lasting >90 days after beginning of rash
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| Evaluable cases of HZ: indisputable cases of HZ, even if atypical or modified by vaccine; clinical assessment
by committee of experts; laboratory assessment by specifically designed polymerase chain reaction (PCR)
assay
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| Results of study: New England Journal of Medicine (2005); 481 cases of HZ in treatment group, 827 in placebo
group; 93% of cases confirmed by VZV DNA in PCR; clinical evaluation committee findings correlated
well with PCR results; participants divided into 2 separately randomized age groups; overall burden of illness
score reduced 61%, well above predetermined 47% criterion for success in older age group; number of
cases of HZ reduced ≈50% and less severe on average; ADLs—vaccine reduction of adverse effects of HZ
similar to its reduction of burden of illness
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| Incidence of PHN: compared to placebo, vaccine reduced incidence of PHN by 66%; although more PHN developed
in patients ≥70 yr of age, incidence reduced proportionately (by 66%) in younger and older groups
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| Incidence of HZ: reduced ≈50% overall, but only 37% in patients ≥70 yr of age; vaccine efficacy diminishes
with age
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| Treatment provided in study: famciclovir given to all patients with suspected HZ (66% received drug within
72 hr of rash onset); patients offered aggressive pain treatment (including opioids); resulting lessening of
disease severity in placebo group led to underestimating impact of vaccine
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| Vaccine safety: no increase in adverse events; vaccine did not cause HZ; 3 times more cases in placebo group
during first 30 days
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| Impact of age: age did not affect impact of vaccine on incidence of PHN; in older age group, slight reduction
of effect of vaccine on burden of illness score; substantial decline in ability of vaccine to decrease incidence
of HZ in older age group; immunology substudy—measured immunity before and after vaccination; level of
cell-mediated immunity declines with advancing age; boost in immunity greater in younger subjects; severity
of illness score >600—“equivalent to >60 days of the worst pain you can possibly imagine”; in participants 60
to 69 yr of age, 9 of 10 cases in placebo group; in participants ≥70 yr of age, 31 in placebo group and 10 in
vaccine group (severity less in vaccine group); vaccine produced 73% reduction in severity of illness score; in
younger group, vaccine mainly prevented HZ; in older group, vaccine mainly attenuated disease
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| How long does vaccine effect last? unknown; patients in immunology substudy followed for 3 yr; efficacy fell
somewhat between 6 wk and 1 yr but remained relatively stable over 3 yr; efficacy well maintained for total of
4 yr; participants continuing to be followed for efficacy
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| Current status: Food and Drug Administration (FDA) licensed vaccine on May 25, 2006; on October 25,
2006, Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices
recommended vaccine (Zostavax) be administered to patients ≥60 yr of age to prevent HZ and PHN, irrespective
of history of shingles (patient history unreliable; immunity after shingles wanes with time); vaccinating
everybody as recommended would reduce new cases of HZ annually by almost 300,000, and cases of PHN by
46,000
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| Questions and answers: disseminated HZ—≥25 or ≥50 lesions at distance from primary dermatome; occurs
in people with cell-mediated immunity problem; treatment of shingles—immune globulin ineffective in prevention
of shingles; by time rash appears and diagnosis made, steroid therapy of no benefit; role of stress—
believed to be risk factor for shingles but unproven; boost in immunity—occurs in adults with exposure to
chickenpox (in response to “silent” reinfection)
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| VACCINES IN THE ELDERLY —Robin McKenzie, MD, Assistant Professor of Medicine, Johns Hopkins
University School of Medicine, and Johns Hopkins Bayview Medical Center, Baltimore, MD
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| Influenza vaccine: annual influenza burden—5% to 20% of US population infected; ≈200,000 hospitalizations,
50% in patients >64 yr of age; persons >65 yr of age account for >90% of 36,000 deaths annually
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| Vaccine efficacy: elderly patients have lower antibody titers after vaccination; among noninstitutionalized
people >60 yr of age, vaccine prevents respiratory illness and hospitalization; in nursing home residents,
50% to 60% efficacy in preventing hospitalization or pneumonia, 80% efficacy in preventing death
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| Cost-effectiveness: reduces health care visits, lost work, and antibiotic use; cost-effective in patients >65 yr of
age who may not be working
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| Two vaccines: live attenuated vaccine for nonimmunocompromised people <50 yr of age; inactivated vaccine
for all others
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| Recommendations for vaccination
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| Specific recommendation for 2 groups: people at risk for severe complications; people who live with or
care for people at risk
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| Vaccination of those at risk: everyone >50 yr of age; nursing home residents; adults and children with certain
chronic diseases (lung; heart; kidney; diabetes; immunodeficiency from HIV or steroid use; at risk
for pulmonary infection due to mechanical problem); children ≤5 yr of age; women who will be pregnant;
travelers
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| Vaccination to prevent spread to those at risk: health care workers; caregivers; household contacts; anybody
who wants vaccine
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| Recommendations likely to change: most infections occur in school-age children; vaccinating children
would prevent spread to others; recommendation likely to include children ≤18 yr of age, then expand
to their contacts and caregivers; may become universal
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| Pneumococcal vaccine: almost 1 million cases of community acquired pneumonia (CAP) each year in elderly;
Streptococcus pneumoniae most common cause of CAP; vaccine not proven efficacious in preventing
CAP; effective, however, in preventing bacteremia; pediatric conjugated vaccine has significantly lowered
rate of invasive pneumococcal disease in elderly (example of herd immunity)
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| Recommendations for vaccination: everyone >65 yr of age; nursing home residents; adults and children with
certain chronic diseases (lung; heart; kidney; diabetes; immunocompromised patients; alcoholism; chronic
liver disease; asplenia; cerebrospinal fluid [CSF] leaks); Alaskan Native and American Indian populations
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| Recommendations likely to change: rates of invasive pneumococcal disease significantly higher in blacks;
medical journal editorials recommend vaccinating all smokers, blacks, and everyone >50 yr of age
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| Tetanus, diphtheria, acellular pertussis (Tdap) vaccine: recommended for adults ≤65 yr of age; 3 stages of
pertussis (whooping cough)—upper respiratory syndrome; paroxysmal (severe coughing with inspiratory
whoop); convalescent (coughing for weeks); complications—pneumonia; rib fractures; cough syncope; urinary
incontinence; inguinal hernia; herniated lumbar disc; angina; weight loss; also—many medical visits
for cough relief; about one-half million symptomatic cases in adults each year; infectious outbreaks seen,
eg, in hospitals
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| Burden of disease from pertussis: expensive medical visits; extensive work-ups; missed work; hospitalization;
brunt of illness—in children <1 yr of age; vaccination recommended for adults in contact with children
<1 yr of age
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| Recommendations for Pertussis vaccination: single dose in those 11 to 65 yr of age to replace tetanus vaccination
given 10 yr earlier; 2 yr after last tetanus vaccination—adults in contact with children <1 yr of age;
health care workers with patient contact
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Suggested Reading
Fedson DS: The conjugate vaccine and invasive pneumococcal disease. N Engl J Med 349:714, 2003; Greene
CM et al: Active Bacterial Core Surveillance Program of the Emerging Infections Program Network. Preventability
of invasive pneumococcal disease and assessment of current polysaccharide vaccine recommendations
for adults: United States, 2001-2003. Clin Infect Dis 43:141, 2006;.Herpes zoster vaccine (Zostavax). Med Lett
Drugs Ther 48:73, 2006; Hornberger J et al: Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic
neuralgia in older adults. Ann Intern Med 145:317, 2006; Jackson LA et al: Vaccine Safety Datalink.
Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med 348:1747, 2003; Kimberlin
DW et al: Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med 356:1338, 2007; Konradsen
HB et al: The conjugate vaccine and invasive pneumococcal disease. N Engl J Med 349:714, 2003;
Kretsinger K et al: Centers for Disease Control and Prevention; Advisory Committee on Immunization Practices;
Healthcare Infection Control Practices Advisory Committee. Preventing tetanus, diphtheria, and pertussis
among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations
of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the
Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel.
MMWR Recomm Rep 55:1, 2006; McNeil SA et al: Comparison of the safety and immunogenicity of
concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed
combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults. Vaccine
25:3464, 2007; Meyer CU et al: Cellular immunity in adolescents and adults following acellular pertussis vaccine
administration. Clin Vaccine Immunol 14:288, 2007; Oxman MN et al: Shingles Prevention Study Group.
A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271, 2005;
Rothberg MB et al: Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in
older adults. Clin Infect Dis 44:1280, 2007; Summaries for patients. Cost-effectiveness of a vaccine to prevent
herpes zoster (shingles) in older adults. Ann Intern Med 145:I14, 2006; Thompson WW et al: Influenza-associated
hospitalizations in the United States. JAMA 292:1333, 2004; Whitley RJ et al: Seasonal and pandemic
influenza: recommendations for preparedness in the United States. J Infect Dis 194 Suppl 2:S155, 2006; Whitney
CG et al: Active Bacterial Core Surveillance of the Emerging Infections Program Network. Decline in invasive
pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med
348:1737, 2003; Zimmerman RK: Recent changes in influenza vaccination recommendations, 2007. J Fam
Pract 56:S12, 2007.
Educational Objectives
| The goal of this program is to provide an understanding of the new vaccine for herpes zoster and the latest vaccination
recommendations for elderly patients. After hearing and assimilating this program, the clinician will be
better able to:
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| 1. Explain the etiology of herpes zoster and postherpetic neuralgia.
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| 2. Select patients to receive the new vaccine for herpes zoster.
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| 3. Provide antiviral therapy for outbreaks of herpes zoster.
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| 4. Implement recommendations for providing patients with the influenza and pneumococcal vaccines.
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| 5. Prevent pertussis in patients ≥65 yr of age by offering the tetanus, diphtheria, pertussis (Tdap) vaccine.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health
care and not a proprietary business or commercial interest. For this program, the following has been disclosed:
Dr. Oxman— Merck and Co, Inc (research grant for the Shingles Prevention Study)
Acknowledgements
Dr. Oxman was recorded at Topics and Advances in Internal Medicine, sponsored by the University of California,
San Diego, School of Medicine, February 22-28, 2007, in San Diego; Dr. McKenzie, at the 34th Annual Current
Topics in Geriatrics, sponsored by Johns Hopkins University School of Medicine, February 15-17, 2007, in Baltimore,
MD. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the
production of this program.
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