1

Understanding Herpes Zoster & the Critical Importance of

Herpes Zoster Vaccine

W. Paul McKinney, MDUniversity of Louisville

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Pre-Test Questions

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9

Understanding Herpes Zoster:The Disease

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1. How many of you have had chickenpox (varicella)?

2. How many of you are at risk for herpes zoster?

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Diagnosis of Zoster

© Diepgen TL, Yihune G et al. Dermatology Online Atlas (www.dermis.net). Reprinted with permission.

Dermatomal distribution of rash

Grape-like clustering of lesions

© Phototake. Reprinted with permission.

Image courtesy of Thomas P. Habif, MD.

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The Family of Human Herpes Viruses (HHV)

• HHV-1H. simplex 1• HHV-2H. simplex 2• HHV-3Varicella-zoster virus• HHV-4Epstein-Barr virus• HHV-5Cytomegalovirus• HHV-6Roseola infantum/exanthem subitum/Sixth

Disease• HHV-7ES (?)• HHV-8Kaposi’s sarcoma

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Electron Micrograph: VZV

http://web.uct.ac.za/depts/virology/teaching/notes/herpes.htm

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EM: VZV

Image courtesy of Dr. Frank Fenner, John Curtin School of Medical Research, Australian National University, Canberra, Australia.

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Clinical Features of Zoster

• Tends to be less severe in children, young adults• Prodrome with headache, photophobia, abnormal skin

sensations/pain may precede rash by days/weeks• Pain may be dull, burning, throbbing, stabbing or tingling

and lead to misdiagnosis: MI, renal/gallstones, appendicitis Above symptoms may occur without subsequent rash: zoster sine

herpete

• Rash is unilateral, present in 1-2 adjacent dermatomes• Thoracic, cervical, ophthalmic regions most common• Rash appears as progression…

maculopapulesvesiclesclusterspustulesulcerscrusts …And lasts 7-10 days, healing in 2-4 wks

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Risk Factors for Zoster1

Prior chickenpox infection: 98-99.5% of Americans

Advancing age and declining cell-mediated immunity (CMI)– VZV-specific immunity declines with age– Altered CMI may also be due to immunosuppressive

illness or medical treatments

Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340–346.

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Epidemiology of Herpes Zoster

• Herpes zoster (shingles) results from the reactivation of the varicella-zoster virus (VZV).1

• More than 90% of US adults are susceptible to zoster.1

– There is no way to predict who will develop zoster.2

• Estimated 1 million cases per year in the United States3

• Incidence and severity of zoster increase with advancing age1,4

– Of the estimated 1 million cases per year, approximately 40% to 50% occur in individuals ≥60 years of age.3

– By 85 years of age, approximately 50% of individuals will have had zoster.5

– Lifetime risk may be as high as 20%5 or even 33%

1. Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340–346. 2. Whitley RJ. In: Watson CPN, Gershon AA, eds. Herpes Zoster and Postherpetic Neuralgia, 2nd Revised and Enlarged Edition. Vol 11. Amsterdam, The Netherlands: Elsevier Science B.V.: 2001:65–78. 3. Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA. J Gen Intern Med. 2005;20:748–753. 4. Arvin AA. Fields Virology. 4th ed. Vol 2. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:2731–2767. 5. Schmader KE. Clin J Pain. 2002;18:350–354.

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Zoster Incidence

2.02.9

4.6

1.1 1.4

6.9

9.5

10.9

0

2

4

6

8

10

12

14

16

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pe

rso

n-y

ea

rs*

(95

% C

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Age (years) 0–14 15–29 30–39 40–49 50–59 60–69 70–79 80

Cases (N=9,152) 397 527 600 1,213 1,989 1,778 1,692 956

*Age-specific incidence rates (across both sexes) from a healthcare claims database of more than 2.8 million individuals for the years 2000–2001 were sex adjusted to the 2000 US population. Insinga RP, Itzler RF, Pellessier JM, Saddier P, Nikas AA.J Gen Intern Med. 2005;20:748–753.

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The Aging Population

Source: US Bureau of the Census.

1960

Male Female(Age)

6 5 4 3 2 1 0 0 1 2 3 4 5 6

Percentage of total population

1990

Male Female(Age)

6 5 4 3 2 1 0 0 1 2 3 4 5 6

Percentage of total population

2020

Male Female(Age)

6 5 4 3 2 1 0 0 1 2 3 4 5 6

Percentage of total population

Baby Boomers

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Other Specific Risks for Zoster

• Early infection (age < 2 months) increases risk of zoster by age 12 by factor of 30+

• Varicella vaccine: – Risk for zoster in immune compromised recipients of varicella

vaccine is reduced by 2/3– Risk of zoster for immunocompetent recipients of varicella

vaccine likely lower, but long term followup in progress– Incidence in women in 11 to 35% higher

• Incidence in African Americans is 54-75% lower than whites

• No clear seasonal pattern• Linkage to stress is uncertain

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Zoster Risk Among the Immunocompromised

• Among persons with solid or hematologic tumors, Hodgkin’s Disease pts at especially high risk: 27%

• High rates among stem cell transplant (13-55%) and solid organ transplant recipients (5-17%). Incidence highest just after transplant. Most cases occur within 1 year.

• HIV+ patients have 12-17 times the incidence of zoster of HIV- persons; risk even higher among children

• Persons with SLE, RA, Crohn’s, UC are at higher risk, probably due to immunosuppressive treatment

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The Effect of Re-Exposure to VZV

• Ongoing exposure to chickenpox, zoster may reduce an individual’s risk for zoster:

• Study in the UK showed 74% reduction in zoster risk for those with 3-4 varicella contacts compared to none over a 10 year period

• Another British study showed 25% decrease in zoster incidence for adults living with children, with effect persisting for 20 years

• Conflicting evidence for this is higher zoster incidence in women and a Japanese study showing no effect of repeated exposures in children

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Risk of Recurrent Zoster

• Olmsted County, MN study showed no evidence that one episode of zoster reduces the subsequent recurrence rate:– 24 of 1669 persons with zoster over 6 yr period have

another episode

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Hospitalization and Death Rates

• Again in Olmsted Co, 3% of zoster pts hospitalized

• Almost all zoster deaths are in the elderly, who have a 10x higher mortality

• Overall: – 8.7% death rate among the immune compromised– 3.7% death rate among the immunocompetent

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Latency of VZV Established after Primary Infection (Chickenpox)

• Established by retrograde axonal transport of virus from skin to dorsal root ganglia

• Present in 1% to 7% of sensory ganglion neurons

• Each ganglion cell has <10 viral genomic copies• Intensity of primary infection linked to latency

burden

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VZV Latency Maintained by Cell-Mediated Immunity (CMI)

• CMI effectiveness maintained through immunologic boosting– Endogenous boosting: Clinical or subclinical

reactivation– Exogenous boosting: exposure to other active cases

Anti-VZV Ab levels per se are not critical in preventing re-activation:– Rather, rise in Ab levels and presence and rise in

CD4 T-cells after immunization are predictive of protection

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Reactivation of VZV

Advances in the Treatment and Prevention of Herpes Zoster and Postherpetic Neuralgia Lawrence D. Gelb, MD Michael D. Hogue, PharmD, Myron J. Levin, MD

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Zoster Complications

Image courtesy of Charles E. Crutchfield III, MD.

Zoster Ophthalmicus • Occurs in 10-25% of zoster cases• Keratitis in 2/3 of these• Scarring and visual loss may result• Refer to ophthalmologist

1. Pavan-Langston D. In: Watson CPN, Gershon AA, eds. Herpes Zoster and Postherpetic Neuralgia, 2nd Revised and Enlarged Edition. Vol 11. Amsterdam, The Netherlands: Elsevier Science B.V.;2001:119–129.

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Other VZV Complications

• Ramsay Hunt Syndrome: peripheral CN7 palsy found with vesicular lesions on tongue, hard palate or ear– may also have vertigo, hearing/taste loss, tinnitus– results from geniculate ganglion reactivation

Motor weakness, autonomic dysfunction, focal neurologic deficits may be seen

Rarely, myelitis, aseptic meningitis, meningoencephalitis also occur

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VZV in Immunocompromised Hosts

Tend to have more severe and prolonged rash Up to 1/3 may have true cutaneous dissemination Disssemination is a marker for viremia that may involve

lungs, liver, GI tract, brain…resulting in case fatality rate of 5-15%

Risk for neurologic complications greatly increased Risk for PHN is no different HIV pts: less severe features and lower rate of visceral

dissemination than other compromised hosts– May develop unique complication: acute retinal necrosis,

blindness

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Diagnosing VZV

• Not usually required in classic clinical cases, but when needed:

• Tzanck smears for multinuclear giant cells: positive also in herpes simplex

• Viral cultures take several days, may be falsely negative• Direct fluorescent Ab (DFA) of lesion scraping or biopsy

is sensitive and fast• Polymerase chain reaction (PCR) for viral DNA also

rapid, sensitive, but less available

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Transmission of Zoster

• Vesicles have high concentrations of VZV• Contagious from eruption until crusting• Zoster much less transmissible than chickenpox:

Infection rates 15% vs 70%• Transmission between pts and from pthealthcare

workers seen in hospital. • Transmission from healthcare workers to pts NOT seen• Covered lesions much less likely to transmit infection

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Healthcare Personnel with Zoster

• Avoid all contact with pregnant women, premature/low birth weight infants, and immuncompromised pts until lesions crust.

• Some hospitals exclude workers from any pt contact until lesions crust.

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Acute Zoster-Associated Pain

Prodrome May precede the rash by variable period Occurs in the majority of zoster patients 60 years of age

and older2 May lead to misdiagnosis

Acute pain Pain often described as sharp, stabbing, throbbing,

burning, itching, or hot.

1. Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340–346. 2. Oxman MN. In: Arvin AM, Gershon AA, eds.Varicella-Zoster Virus, Virology and Clinical Management. Cambridge, UK. Cambridge University Press; 2000:246–275.

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Postherpetic Neuralgia (PHN)

Postherpetic neuralgia (PHN) is a potentially debilitating sequela of zoster,1 persisting for months or years.2

No consensus on duration of ongoing pain to define PHN: 30 days to 6 months post rash

May result from axonal/cell body degeneration, scarring of dorsal root ganglion

Common features of PHN include either constant or episodic pain and allodynia (pain provoked by innocuous stimuli).3

– Allodynia is present in approximately 55% of acute zoster patients, but may affect up to 90% of patients with postherpetic neuralgia.4

1. Oxman MN. In: Arvin AM, Gershon AA, eds. Varicella-Zoster Virus: Virology and Clinical Management. Cambridge, UK: Cambridge University Press; 2000:246–275. 2. Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340–346. 3. Dworkin RH, Portenoy RK. Pain. 1996;67:241–251. 4. Bowsher D. In: Watson CPN, Gershon AA, eds. Herpes Zoster and Postherpetic Neuralgia, 2nd Revised and Enlarged Edition. Vol 11. Amsterdam, The Netherlands: Elsevier Science B.V.; 2001:143–147.

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Risk Factors for PHN

• Age is primary risk factor: Persons over 50 are 27x more likely to have PHN than

those under 50 About 80% of PHN patients are age 50 and over

• PHN incidence rate among zoster patients: 18%, 13%, and 10% based on cutoff of 30, 60, 90

day pain duration in Olmsted County 30%, 18%, 13% in placebo group of zoster vaccine

study

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Comparison of Pain Scores for Various Conditions

Acute Pain Conditions Chronic Pain Conditions

Less Pain

More Pain

Katz and Melzack compared total pain rating index scores from multiple studies of chronic pain and acute pain of diverse causes, using the Short-form McGill Pain Questionnaire. Pain scale indexes ranged from 0 to 50.

0

10

20

30

40

50

Abdominal hysterectomy

Acute headache

ZosterLabor pain

Postsurgical painMucositis

Angioplasty sheath removal

Postherpetic neuralgia

Chronic cancer pain

Fibromyalgia

Rheumatoid arthritisOsteoarthritisArthritisMusculoskeletal painAtypical facial pain

Adapted from Surgical Clinics of North America, Vol 79, Katz J, Melzack R, Measurement of Pain, pp 231–252. Copyright ©1999, with permission from Elsevier.

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Treatment of Zoster and PHN

• Acyclovir, famciclovir, valacyclovir all FDA approved for zoster in immune competent pts: all reduce duration of shedding, number of lesions, time to healing, severity/duration of pain and risk for PHN. (All studies started tx within 72 hrs.)

• Corticosteroids (3 wk oral tapering dose) PLUS acyclovir: reduced acute pain and time to healing, but no additive effect vs risk of PHN. No effect of topical steroids

• Keep lesions clean/dry, avoid topical antibiotics routinely, cover lesions

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Treatments for Zoster Pain and Postherpetic Neuralgia

Zoster•Antivirals, as stated

Analgesics2

– Non-narcotics– Narcotics

Postherpetic neuralgia Analgesics1

– Non-narcotics– Narcotics

Topical agents1

Anticonvulsants1

Consultation with a pain management specialist may be necessary1

1. Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340–346. 2. Stankus SJ, Dlugopolski M, Packer D. Am Fam Physician. 2000;61:2437–2444.

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Summary

Reactivation of varicella-zoster virus results in zoster (shingles), which is characteristically dermatomal in distribution.1

An estimated 1 million cases of zoster occur annually in the United States.2

– There is no way to predict who will develop zoster.3

Advanced age and waning cell-mediated immunity are defined risk factors.1

Postherpetic neuralgia is one of the most severe complications of zoster.4

1. Straus SE, Oxman MN. In: Freedberg IM, Eisen AZ, Wolff K, et al, eds. Fitzpatrick’s Dermatology in General Medicine. 5th ed. Vol 2. New York, NY: McGraw-Hill; 1999:2427–2450. 2. Insinga RP, Itzler RF, Pellisier JM, Saddier P, Nikas AA. J Gen Intern Med. 2005:748-753. 3. Whitley RJ. In: Watson CPN, Gershon AA, eds. Herpes Zoster and Postherpetic Neuralgia 2nd Revised and Enlarged Edition. Vol 11. Amsterdam, The Netherlands, Elsevier Science B.V.; 2001:65–78. 4. Oxman MN. In: Arvin AM, Gershon AA, eds. Varicella-zoster virus, virology and clinical management. Cambridge, UK: Cambridge University Press;2000:246–275.

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The Critical Importance of Herpes Zoster Vaccine

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Description

Lyophilized preparation of the Oka/Merck strain of live, attenuated VZV.

Each 0.65-mL dose contains a minimum of 19,400 plaque-forming units (PFU), or 14x the potency of varicella vaccine

Several excipients: porcine gelatin, residual MRC-5 cell DNA, protein; trace neomycin & bovine calf serum; NO thimerosal or other preservatives

Administer subcutaneously in deltoid region No booster dose licensed

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Herpes Zoster Vaccine

HZV is indicated for the prevention of herpes zoster (shingles) in individuals 60 years of age and older.

HZV has no role in the treatment of zoster or postherpetic neuralgia (PHN).

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Clinical Pharmacology: The Shingles Prevention Study Design

Subjects EnrolledN=38,546

Age 60 to 69 years

n=20,747

Age ≥70 yearsn=17,799

Zoster vaccinen=10,378

Placebon=10,369

Zoster vaccinen=8,892

Placebon=8,907

Adverse Event (AE) Substudy

n=6,616

Immunogenicity Substudyn=1,395

Oxman MN, Levin MJ, Johnson GR, et al. N Engl J Med. 2005;352:2271–2284.

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Patient Demographics in the Shingles Prevention Study

CharacteristicVaccine Group

N=19,270Placebo Group

N=19,276Age n (%)60 to 69 years 10,378 (53.9) 10,369 (53.8)70 years 8,892 (46.1) 8,907 (46.2)Gender n (%)Male 11,403 (59.2) 11,357 (58.9)Female 7,867 (40.8) 7,919 (41.1)Race n (%) White 18,393 (95.4) 18,381 (95.4)Black 395 (2.0) 420 (2.2)Hispanic 265 (1.4) 248 (1.3)Other or unknown 217 (1.1) 227 (1.2)

Oxman MN, Levin MJ, Johnson GR, et al. N Engl J Med. 2005;352:2271–2284.

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Prevention of Herpes Zoster

Nu

mb

er o

f zo

ster

cas

es

Age (years)

–64%(95% CI: 56%, 71%)

–41%(95% CI: 28%, 52%)

–18%(95% CI: –29%, 48%)

315

122156

47

261

334

642

370

100

200

300

400

500

600

700

Overall 60–69 70–79 ≥80

Placebo

HZV

–51%(95% CI: 44%, 58%)

Incidence rate of zoster per 1,000 person-years11.1 10.8 11.4 12.25.4 3.9 6.7 9.9

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Postherpetic Neuralgia* in the Shingles Prevention Study

*Zoster-associated pain rated as ≥3 on a 10-pt scale and occurring or persisting at least 90 days after rash onset.†Age-adjusted estimate based on the age strata (60-69 and ≥70 years of age) at randomization.

0

Overall 60–69 70–79 ≥80Age (years)

Number of PHN Cases 80 23 45 1227 8 12 7

25.5

8.6 6.6 7.7

18.917.2

6.9

12.510

20

30

40

50

% o

f Z

ost

er C

ases

wit

h P

ost

her

pet

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–5%(95% CI: –107%, 56%)

–55%(95% CI: 18%, 76%)

–26% (95% CI: –69%, 68%)

–39%†

(95% CI: 7%, 59%)

Placebo HZV

Number of HZ Cases 642 334 261 47315 122 156 37

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Immunogenicity

• VZV specific immunity rises 6 wks after vaccine, not placebo

• Degree of immune response directly correlates with protection

• No Ab threshold for protection evident• CMI responses higher in persons under 70

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Duration of Efficacy

Efficacy declines in year 1 but then stable through year 3

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Specific Complications* of Zoster AmongZoster Cases in the Shingles Prevention Study

ComplicationHerpes Zoster Vaccine

(N = 19,270)Placebo

(N = 19,276)

( n = 321)% Among

Zoster Cases(n = 659)

% Among Zoster Cases

Allodynia 135 42.1 310 47.0

Bacterial Superinfection 3 0.9 7 1.1

Dissemination 5 1.6 11 1.7

Impaired Vision 2 0.6 9 1.4

Ophthalmic Zoster 35 10.9 69 10.5

Peripheral Nerve Palsies (motor) 5 1.6 12 1.8

Ptosis 2 0.6 9 1.4

Scarring 24 7.5 57 8.6

Sensory Loss 7 2.2 12 1.8

N=number of subjects randomizedn=number of zoster cases, including those cases occurring within 30 days postvaccination, with these data available*Complications reported at a frequency of ≥1% in at least one vaccination group among patients with zoster.

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Economic Burden and Cost-Effectiveness (CE)

• Five studies estimated CE of 1 dose of HZV• For vaccine cost of $150, costs were $27,000 to

$112,000 per quality-adjusted life year gained. Result was sensitive to variations in vaccine cost, duration of efficacy, risk of PHN, costs and quality of life scores for zoster and complications

• World Health Organization suggests CE threshold of 3x Gross Domestic Product per capita ($94,000 for USA)

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Adverse Reactions

HZV was evaluated for safety in approximately 21,000 adults.

Shingles Prevention Study Routine safety monitoring

– HZV: n = 15,925; placebo: n = 16,005– Patients were actively followed for safety outcomes through Day

42 postvaccination. – Subjects were followed passively for safety after Day 42

postvaccination to the end of the study. AE Monitoring Substudy

– HZV: n = 3,345; placebo: n = 3,271– Vaccination report cards used to record AEs for

42 days postvaccination– Monthly surveillance for hospitalization 2 to 5 years

postvaccination

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Number of Subjects With ≥1 Serious Adverse Experience (0–42 Days Postvaccination)

in the Shingles Prevention Study

Cohort

HZVn/N%

Placebon/N%

Relative Risk (RR)

(95% CI)

Overall Study Cohort (all ages)

255/18,6711.4%

254/18,7171.4%

1.01 (0.85, 1.20)

60–69 years old 113/10,1001.1%

101/10,0951.0%

1.12(0.86, 1.46)

70–79 years old 115/7,3511.6%

132/7,3331.8%

0.87(0.68, 1.11)

≥80 years old 27/1,2202.2%

21/1,2891.6%

1.36(0.78, 2.37)

AE Monitoring Substudy Cohort(all ages)

64/3,3261.9

41/3,2491.3

1.53 (1.04, 2.25)

60–69 years old 22/1,7261.3%

18/1,7091.1%

1.21(0.66, 2.23)

70–79 years old 31/1,3832.2%

19/1,3671.4%

1.61(0.92, 2.82)

≥80 years old 11/2175.1%

4/1732.3%

2.19(0.75, 6.45)

N = number of subjects in cohort with safety follow-upn = number of subjects reporting an SAE 0–42 days postvaccination

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AE Monitoring Substudy Entire Study Cohort

HZV

N = 3,326Placebo

N = 3,249

HZV

N = 18,671

Placebo

N = 18,717

n (%) n (%) n (%) n (%)

Overall cardiovascular events by body system

20 (0.6) 12 (0.4) 81 (0.4) 72 (0.4)

Coronary artery disease-related conditions*

10 (0.3) 5 (0.2) 45 (0.2) 35 (0.2)

N=number of subjects with safety follow-upn=number of subjects reporting SAE within the category

*CAD-related conditions: angina pectoris, coronary artery disease, coronary occlusion, cardiovascular disorder, myocardial ischemia, & myocardial infarction

Selected Serious Adverse Experiences (SAE) Reported More Frequently After HZV than After Placebo Days 0–42 Postvaccination

in the Shingles Prevention Study

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Injection-Site and Systemic Adverse Experiences

Adverse Experience

HZV(n = 3,345)

%

Placebo

(n = 3,271)%

Injection Site Erythema* Pain/tenderness* Swelling* Hematoma Pruritus Warmth

33.733.424.9 1.4 6.6 1.5

6.48.34.31.41.00.3

Systemic Headache 1.4 0.8

Reported by vaccine report card in ≥1% of adults who received ZOSTAVAX or placebo (0 to 42 days postvaccination) in the AE monitoring substudy of the

Shingles Prevention Study

*Designates a solicited adverse experience. Injection-site adverse experiences were solicited only from Days 0–4 postvaccination.

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Adverse Events Occurring After Day 42 Postvaccination

AE Monitoring Substudy subjects in the Shingles Prevention Study were monitored for hospitalizations through monthly automated phone queries and the remainder of subjects were passively monitored for safety in this study from Day 43 postvaccination through study end.

Over the course of the study (4.9 years), 51 individuals (1.5%) receiving HZV were reported to have congestive heart failure (CHF) or pulmonary edema compared to 39 individuals (1.2%) receiving placebo in the AE Monitoring Substudy; 58 individuals (0.3%) receiving HZV were reported to have congestive heart failure (CHF) or pulmonary edema compared to 45 (0.2%) individuals receiving placebo in the overall study.

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Summary: ACIP Rationale for Zoster Vaccine Recommendations

1. Zoster causes substantial morbidity in US: 1 million cases per year, with risk of severe complications

2. Antiviral therapy only partially effective and time dependent.

3. Therapy for PHN inadequate for many

4. HZV appears cost effective by usual comparison

5. Vaccine efficacious, based on reduction in incidence of zoster (51%), PHN (65%), and overall burden of illness (61%)

6. Efficacy, though somewhat reduced, is still present even in oldest age groups

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ACIP Recommendations for Use of HZV

1. All persons aged 60 and over, unless specifically contraindicated. (NOT licensed for those under 60). Prior history of zoster and most chronic medical conditions do not alter the recommendation.

2. Use simultaneously or 4 wks after other live viral vaccines. Non-live vaccines (Td, Tdap, influenza, pneumococcal 23) may be given with, or anytime before or after HZV.

3. Not recommended for those who received varicella vaccine. (This excludes extremely few persons)

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Recommendations for HZV--continued

4. Consider for those anticipating immune suppression with chemotherapy, etc (give HZV at least 14-30 days in advance)

5. Hold antivirals for at least 24 hrs before vaccination. If vaccinated first, use antivirals no earlier than 14 days later.

6. Receipt of blood products not a problem, since pre-existing Ab does not diminish response.

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?

63

Contraindications to HZV

1. Anaphylactic reaction hx to any component (usually neomycin or gelatin)

2. Persons with primary or acquired immune deficiency: leukemia, lymphoma, AIDS or HIV+ with CD4<200 High dose steroids (20 mg/d prednisone for 2 weeks

or more) Stem cell transplant Immune modulators: TNF agents like inflixamab,

etanercept Note: Gamma globulin disorders NOT a contra

3. Pregnancy: rare in the 60+ population

4. Postpone if acute, moderate to severe illness

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Selected Precautions

Transmission Transmission of the vaccine virus has not been reported in

clinical trials. Postmarketing experience with varicella vaccines suggests that

transmission of vaccine virus may occur rarely between vaccinees who develop a varicella-like rash and susceptible contacts.

Transmission of vaccine virus from varicella vaccine recipients without a VZV-like rash has been reported but has not been confirmed.

Vaccinees should be informed of the theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.

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Conditions for Storage

HZV STORE FROZEN at an average temperature of –15°C

(+5°F) or colder until it is reconstituted for injection. Any freezer, including frost-free, that has a separate

sealed freezer door and reliably maintains an average temperature of –15°C or colder is acceptable. Measure and record temp twice per day.

Diluent Store diluent separately at room temperature (20°C to

25°C, 68°F to 77°F) or in refrigerator (2°C to 8°C, 36°F to 46°F).

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Dosage and Administration

For Subcutaneous Administration: deltoid region: Single Dose

Reconstitution procedure Reconstitute immediately upon removal from

freezer. To reconstitute, first withdraw entire contents of

diluent vial into a syringe; inject all the diluent into a vial of lyophilized vaccine; gently agitate to mix thoroughly.

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Administration

Injection procedure: Withdraw entire contents of reconstituted vaccine into a syringe. Inject total volume SC, preferably into upper arm. Administer immediately after reconstitution.

Discard reconstituted vaccine if not used within 30 minutes.

Do not freeze reconstituted vaccine.

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Consider Vaccinating Appropriate Patients in Your Practice

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Adult Vaccination Schedule

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Good General Immunization Practices

• Link HZV to other indicated vaccinations: eg influenza• Use standing orders to facilitate implementation• Nursing home/chronic care facility patients should be

included• Report adverse events after vaccination to VAERS:

FDA’s Vaccine Adverse Event Reporting System: telephone, web-based access

• Report any administration errors to VAERS: eg, giving HZV instead of varicella vaccine to a child. Varicella vaccine NOT indicated for prevention of zoster.

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Physician Barriers to Vaccination

Vaccine Issues Patients’ vaccine safety concerns

Practical issues Urgent medical concerns No patient immunization history

Education Ambiguous vaccination guidelines Lack of patient-oriented vaccine information

Cost Inadequate reimbursement

Szilagyi PG, Shone LP, Barth R, et al. Prev Med. 2005;40:152–161.

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Patient Barriers to Vaccination

• Did not know the shot was needed• Doctor did not recommend the shot• Did not think of it/missed it• Thought the shot could cause the disease• Thought the shot would have side effects• Did not think the shot would prevent disease• Do not like shots or needles• Shot not worth the money

Centers for Disease Control and Prevention. MMWR. 1999;48:886–890.

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Screening Questionnaire for Adult Immunization

Are you sick today?

Do you have allergies to medications, food, or any vaccine?

Have you ever had a serious reaction after receiving a vaccination?

Do you have cancer, leukemia, AIDS, or any other immune system problem?

Do you take cortisone, prednisone, other steroids, or anticancer drugs, or have you had x-ray treatments?

During the past year, have you received a transfusion of blood or blood products, or been given a medicine called immune (gamma) globulin?

For women: Are you pregnant or is there a chance that you could become pregnant within the next 3 months?

Have you received any vaccinations in the past 4 weeks?

Adapted from the Immunization Action Coalition. Available at: www.immunize.org/catg.d/p4065scr.pdf.

Yes No Don’t know

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Standards for Adult Immunization Practices

Make vaccinations available Identify and minimize barriers

Assess patients’ vaccination statusCommunicate effectively with patients

Educate patients about the risks and benefits of vaccination

Administer and document vaccinations properly Develop office protocols

Implement strategies to improve vaccination rates Patient reminders

Partner with the community

Poland GA, Shefer AM, McCauley M, Webster PS, Whitley-Williams PN, Peter G, and the National Vaccine Advisory Committee. Am J Prev Med. 2003;25:144–150.

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Clinical Practice Recommendation

Practice Recommendation: • Zoster vaccine is recommended for all adults age 60 and above.

Evidence-Based Source: • National Guidelines Clearinghouse

Web Site of Supporting Evidence: • http://www.guideline.gov/summary/summary.aspx?

doc_id=12093&nbr=006222&string=zoster+AND+vaccine

Strength of Evidence: • Class A: Randomized, controlled trial; Class M: Meta-analysis, Systemic review,

Decision analysis, Cost-effective analysis; Class R: Consensus statement, Consensus report, Narrative review

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Clinical Practice Recommendation

Practice Recommendation:• A history of prior shingles disease is not a contraindication to immunizing patients

over age 60 against zoster/shingles.

Evidence-Based Source:• Institute for Clinical Systems Improvement

Web Site of Supporting Evidence: • http://www.icsi.org/immunizations/immunizations__guideline_.html

Strength of Evidence:• Class A: Randomized, controlled trial; Class M: Meta-analysis, Systemic review,

Decision analysis, Cost-effective analysis; Class R: Consensus statement, Consensus report, Narrative review

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Post-Test Questions

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