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1
Understanding Herpes Zoster & the Critical Importance of
Herpes Zoster Vaccine
W. Paul McKinney, MDUniversity of Louisville
2
Pre-Test Questions
3
?
9
Understanding Herpes Zoster:The Disease
10
1. How many of you have had chickenpox (varicella)?
2. How many of you are at risk for herpes zoster?
11
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.
12
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
13
Electron Micrograph: VZV
http://web.uct.ac.za/depts/virology/teaching/notes/herpes.htm
14
EM: VZV
Image courtesy of Dr. Frank Fenner, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
15
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
16
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.
17
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.
18
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
Ra
te p
er
1,0
00
pe
rso
n-y
ea
rs*
(95
% C
I)
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.
19
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
20
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
21
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
22
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
23
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
24
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
25
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
26
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
27
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
28
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.
29
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
30
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
31
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
32
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
33
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.
34
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.
35
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.
36
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
37
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.
38
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
39
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.
40
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.
41
The Critical Importance of Herpes Zoster Vaccine
42
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
43
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).
44
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.
45
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.
46
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
47
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
ic N
eura
lgia
–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
48
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
49
Duration of Efficacy
Efficacy declines in year 1 but then stable through year 3
50
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.
51
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)
52
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
53
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
54
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
55
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.
56
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.
57
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
58
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)
59
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.
60
?
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
64
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.
65
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).
66
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.
67
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.
68
Consider Vaccinating Appropriate Patients in Your Practice
69
Adult Vaccination Schedule
70
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.
71
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.
72
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.
73
74
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.
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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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