Presentation is loading. Please wait.

Presentation is loading. Please wait.

Understanding Herpes Zoster & the Critical Importance of Herpes Zoster Vaccine W. Paul McKinney, MD University of Louisville Welcome to this Merck.

Similar presentations


Presentation on theme: "Understanding Herpes Zoster & the Critical Importance of Herpes Zoster Vaccine W. Paul McKinney, MD University of Louisville Welcome to this Merck."— Presentation transcript:

1 Understanding Herpes Zoster & the Critical Importance of Herpes Zoster Vaccine W. Paul McKinney, MD University of Louisville Welcome to this Merck Medical Forum, Changing the Paradigm for Herpes Zoster Disease. During this presentation, we will discuss zoster and its complications, and will provide an overview of ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)].

2 Pre-Test Questions

3 ?

4 Which of the following is/are true statements?
Herpes zoster results from the reactivation of the varicella-zoster virus (VZV). More than 90% of US adults are susceptible to zoster. Estimated 1 million cases per year in the United States. Incidence and severity of zoster increase with advancing age. All of the above Answer: 5 – all of the above; ARS tech: do not display results or correct answer

5 The preferred rapid test for distinguishing between H. simplex and H
The preferred rapid test for distinguishing between H. simplex and H. zoster is: Viral culture Direct fluorescent antibody (DFA) Tzanck prep Wright stain None of the above Need correct answer; ars tech: do not display results or correct answer

6 Which of the following reasons is/are valid for recommending against use of Herpes Zoster Vaccine?
History of anaphylaxis to neomycin Daily use of 5 mg Prednisone Insulin-requiring diabetes mellitus All of the above Answer: 4 – all of the above; ars tech: do not display results or correct answer

7 You see a 64 year old man with a diagnosis of melanoma, currently on a course of chemotherapy. Which of the following is a valid reason for deferring herpes zoster vaccine in this situation? A prior history of shingles Current chemotherapy Symptoms of a cold with temperature of F. All of the above None of the above Answer: 2 – chemotherapy; ars tech: do not display results or correct answer

8 You are advising one of your patients about receiving herpes zoster vaccine. She has several grandchildren and a pregnant daughter. Which of the following is a true statement concerning risk of transmission after vaccination? Transmission of the vaccine virus has been reported in clinical trials. There is a theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox. There is no risk of transmitting the attenuated vaccine virus to a susceptible individual. None of the above Answer: 2 - There is a theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.; ars tech: do not display results or correct answer

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? How many of you have had chickenpox (varicella)? How many of you have had shingles (herpes zoster)?

11 Diagnosis of Zoster Dermatomal distribution of rash
Grape-like clustering of lesions Diagnosis of Zoster The rash associated with zoster is distinctive and in most cases can be accurately diagnosed by clinical appearance alone.1,2 The lesions appear as grape-like erythematous clusters of vesicles arranged in a unilateral linear pattern along 1, or occasionally 2, adjacent dermatomes. The rash does not cross the midline.1 A close-up image of clustered vesicles is shown in the left panel. The center panel depicts zoster affecting a cervical dermatome. Approximately 50% of zoster cases involve the thoracic dermatomes, especially T5 to T12.3 The panel on the right depicts a thoracic dermatomal distribution of zoster. If the diagnosis is uncertain because of atypical presentation, several laboratory tests are available to help confirm the diagnosis.2 Immunofluorescence or immunoperoxidase staining of vesicle material is used to detect viral antigens.3 Other tests that are available include polymerase-chain reaction techniques, Tzanck smears, and viral cultures.3 Key Point: The classic zoster rash is identifiable as clusters of vesicular lesions distributed along a single dermatome. Image courtesy of Thomas P. Habif, MD. © Phototake. Reprinted with permission. © Diepgen TL, Yihune G et al. Dermatology Online Atlas (www.dermis.net). Reprinted with permission. References: 1. Lycka BAS, Williamson D, Sibbald RG. Dermatologic aspects of herpes zoster. 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.; 2001:97–106. 2. Gnann JW, Whitley RJ. Herpes zoster. N Engl J Med. 2002;347:340–346. 3. Straus SE, Oxman MN. Varicella and herpes zoster. 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.

12 The Family of Human Herpes Viruses (HHV)
HHV-1 H. simplex 1 HHV-2 H. simplex 2 HHV-3 Varicella-zoster virus HHV-4 Epstein-Barr virus HHV-5 Cytomegalovirus HHV-6 Roseola infantum/exanthem subitum/Sixth Disease HHV-7 ES (?) HHV-8 Kaposi’s sarcoma

13 Electron Micrograph: VZV

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… maculopapulesvesiclesclusterspustulesulcerscrusts …And lasts 7-10 days, healing in 2-4 wks

16 Risk Factors for Zoster1
Prior chickenpox infection: % 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 Risk Factors for Zoster A history of chickenpox puts an individual at risk for zoster.1 Other well-defined risk factors for the development of zoster are advancing age and waning cell-mediated immunity.1 Altered CMI may also be due to immunosuppressive illness (eg, acute and chronic leukemias) or immunosppressive therapies (eg, corticosteroids).1 Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340–346. Reference: 1. Gnann JW, Whitley RJ. Herpes zoster. 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% Epidemiology of Herpes Zoster Herpes zoster, commonly known as “zoster” or simply shingles, is the clinical manifestation of the reactivation of varicella-zoster virus (VZV), which as a primary infection, produces chickenpox (varicella).1 In the United States, more than 90% of adults are susceptible to zoster.1 There is no way to predict when VZV will reactivate and who will develop zoster.2 It has been estimated from a US claims database that nearly 1 million zoster cases occur annually.3 The incidence is expected to rise as the mean age of the population increases.4 The incidence and severity of zoster also increase with age.1 Of the estimated 1 million cases of zoster per year, approximately 40% to 50% occur in individuals 60 years of age and older.3 It is estimated that by 85 years of age, 50% of individuals will have experienced an episode of zoster.5 The lifetime risk has been estimated to be as high as 20% in the general population.5 Key Point: The majority of the US population is susceptible to zoster and the incidence of this unpredictable disease increases with increasing age. 1. Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340– 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– Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA. J Gen Intern Med. 2005;20:748– Arvin AA. Fields Virology. 4th ed. Vol 2. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:2731– Schmader KE. Clin J Pain. 2002;18:350–354. References: 1. Gnann JW, Whitley RJ. Herpes zoster. N Engl J Med. 2002;347:340–346. 2. Whitley RJ. Herpes zoster: Natural history, diagnosis and therapy. 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. The incidence of herpes zoster in a United States administrative database. J Gen Intern Med. 2005;20:748–753. 4. Arvin AA. Varicella-zoster virus. In: Knipe DM, Howley PM, eds. Fields Virology. 4th ed. Vol 2. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:2731–2767. 5. Schmader KE. Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy. Clin J Pain. 2002;18:350–354.

18 Zoster Incidence Age (years) 0–14 15–29 30–39 40–49 50–59 60–69 70–79
More than 90% of adults in the United States have been infected with VZV and are at risk for zoster.1 This slide shows age-specific zoster incidence rates (across both sexes) from a healthcare claims database of more than 2.8 million individuals for the years 2000–2001 that were sex adjusted to the 2000 US population.2 The incidence of zoster increases with age. About 40% to 50% of the estimated 1 million cases of zoster in the United States each year occur in people age 60 and older.2 Other authors have reported that estimates of the lifetime risk for zoster range from 10% to 20% in the general population.3 The incidence and severity of zoster, as well as the frequency and severity of its complications, increase with age.4 It is estimated that by 85 years of age, 50% of individuals will have had an episode of zoster.5 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. References: 1. Gnann JW, Whitley RJ. Herpes zoster. N Engl J Med. 2002;347:340–346. 2. Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA. The incidence of herpes zoster in a United States administrative database. J Gen Intern Med. 2005;20:748–753. 3. Schmader K. Herpes zoster in older adults. Clin Infect Dis. 2001;32:1481–1486. 4. Johnson RW, Whitton TL. Management of herpes zoster (shingles) and postherpetic neuralgia. Expert Opin Pharmacother. 2004;5:552–559. 5. Schmader KE. Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy. Clin J Pain. 2002;18:350–354.

19 The Aging Population 1990 1960 2020 Male Female Male Female Male
(Age) 6 5 4 3 2 1 Percentage of total population 1990 Male Female (Age) 6 5 4 3 2 1 Percentage of total population Male Female (Age) 6 5 4 3 2 1 Percentage of total population The Aging Population The US population is progressively aging as the Baby Boom generation (born between 1946 and 1964) reaches maturity.1 The ratio of individuals 65 years of age and older has increased from 1:25 in 1900 to 1:8 in The Baby Boomers begin turning 65 years of age in Between 1990 and 2020, the population 65 to 74 years of age is projected by the National Institute on Aging to grow 74% compared with only a 24% growth for the population under 65 years of age.2 As the population ages, you are likely to see more cases of zoster.3 1960 2020 Baby Boomers Source: US Bureau of the Census. References: 1. US Bureau of the Census. From pyramid to rectangle: The progression of aging. Washington, DC: US Dept of Commerce. Economics and Statistics Administration Available at Accessed November 23, 2005. 2. Sixty-five plus in the United States. Bureau of the Census, Issued may Available at: Accessed November 23, 2005. 3. Arvin AM. Varicella-zoster virus. In: Knipe DM, Howley PM, eds. Fields Virology. Vol 2 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:2731–2767.

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 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 Ophthalmicus Occurs in 10-25% of zoster cases
Zoster Complications Zoster Ophthalmicus Occurs in 10-25% of zoster cases Keratitis in 2/3 of these Scarring and visual loss may result Refer to ophthalmologist Patient K. S.: Zoster Ophthalmicus When reactivation involving the first division (ophthalmic) of the trigeminal nerve occurs, the result is zoster ophthalmicus.1,2 Up to 250,000 cases of zoster ophthalmicus (representing approximately 10% to 25% of all zoster cases), occur in the United States each year. Visual morbidity occurs in 50% to 70% of affected individuals. The incidence and severity of zoster ophthalmicus increase with age.1 Image courtesy of Charles E. Crutchfield III, MD. 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. References: 1. Pavan-Langston D. Ophthalmic zoster. 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. 2. Shaikh S, Ta CN. Evaluation and management of herpes zoster ophthalmicus. Am Fam Physician. 2002;66:1723–1732.

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 pthealthcare 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. Acute Zoster-Associated Pain Prodrome Dermatomal pain and sensory abnormalities may precede development of the vesicular rash by 1 to 5 days.1 The abnormal skin sensations can be either constant or intermittent, localized or diffuse, and range from itching or tingling to severe pain.2 A prodrome occurs in the majority of adults >60 years of age, but is uncommon in persons <30 years of age.2 Prodromal pain may mimic several other conditions, such as pleurisy, early glaucoma, myocardial infarction, biliary or renal colic or appendicitis, which may lead to misdiagnosis.2 Acute zoster pain Acute pain has been described as sharp, stabbing, throbbing, burning, itching, or hot.2 Zoster sine herpete Occasionally, patients experience acute segmental neurologic pain but never develop a rash, a condition known as zoster sine herpete.2 1. Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340– Oxman MN. In: Arvin AM, Gershon AA, eds. Varicella-Zoster Virus, Virology and Clinical Management. Cambridge, UK. Cambridge University Press; 2000: 246–275. References: 1. Gnann JW, Whitely RJ. Herpes zoster. N Engl J Med. 2002;347:340–346. 2. Oxman MN. Clinical manifestations of herpes zoster. In: Arvin AM, Gershon AA, eds. Varicella-Zoster Virus, Virology and Clinical Management. Cambridge, UK. Cambridge 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 Postherpetic Neuralgia Postherpetic neuralgia is a potentially debilitating complication of zoster.1 The pain may last for months or occasionally even years.2 A risk factor for postherpetic neuralgia is advancing age.3 Common features of postherpetic neuralgia may include both steady (described as throbbing or burning) and intermittent (described as sharp or shooting) pain and allodynia. Allodynia is pain provoked by a stimulus that is not normally painful, such as the touch of clothing or bedsheets.3,4 Although allodynia is present in approximately 55% of cases of acute zoster, it may complicate 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– Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340– Dworkin RH, Portenoy RK. Pain. 1996;67:241– 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. References: 1. Oxman MN. Clinical manifestations of herpes zoster. 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. Herpes zoster. N Engl J Med. 2002;347:340–346. 3. Dworkin RH, Portenoy RK. Pain and its persistence in herpes zoster. Pain. 1996;67:241–251. 4. Bowsher D. Pain, sensory change, and allodynia in postherpetic neuralgia. 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
More Pain 50 Acute Pain Conditions Chronic Pain Conditions 40 30 Abdominal hysterectomy Acute headache Zoster Labor pain Postsurgical pain Mucositis Angioplasty sheath removal Postherpetic neuralgia Chronic cancer pain Fibromyalgia Rheumatoid arthritis Osteoarthritis Arthritis Musculoskeletal pain Atypical facial pain 20 Comparison of Pain Scores for Various Conditions Although the rash is the most distinctive feature of zoster, the most frequently debilitating symptom is pain. Katz and Melzack compared total pain rating index scores from multiple studies of chronic and acute pain of diverse causes using the Short-form McGill Pain Questionnaire.1 The figure shows the comparison of the total pain scores for a variety of conditions—the higher the score, the greater the intensity of pain.1 Note the ranking of pain in both postherpetic neuralgia and zoster in the selected pain conditions shown.1 10 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. 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. Less Pain Reference: 1. Katz J, Melzack R. Measurement of pain. Surg Clin North Am. 1999;79:231–252.

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
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 Treatments for Zoster and Postherpetic Neuralgia Treating zoster and postherpetic neuralgia can be difficult, often requiring a multifaceted approach. Zoster is often treated with antiviral therapy, analgesics, and supportive care.1 Ideally, antiviral therapy should begin within 72 hours of the onset of symptoms.1 A variety of therapeutic approaches have been used in efforts to ameliorate postherpetic neuralgia, including the following1: Analgesics, including non-narcotics and narcotics Topical agents Anticonvulsants For patients with severe, intractable pain, referral to a pain management specialist may be necessary.1 1. Gnann JW, Whitley RJ. N Engl J Med. 2002;347:340– Stankus SJ, Dlugopolski M, Packer D. Am Fam Physician. 2000;61:2437–2444. Reference: 1. Gnann JW, Whitley RJ. Herpes zoster. N Engl J Med. 2002;347:340–346. 2. Stankus SJ, Dlugopolski M, Packer D. Management of herpes zoster (shingles) and postherpetic neuralgia. 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 Summary Reactivation of varicella-zoster virus in the dorsal root ganglia results in the disease zoster.1 The characteristic cutaneous eruption of zoster usually occurs in a unilateral dermatomal distribution.1 An estimated 1 million cases of zoster occur per year in the United States.2 There is no way to predict who will develop zoster.3 The 2 major defined risk factors for zoster are older age and waning cell-mediated immunity.1 Postherpetic neuralgia is a complication 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– Insinga RP, Itzler RF, Pellisier JM, Saddier P, Nikas AA. J Gen Intern Med. 2005: 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– Oxman MN. In: Arvin AM, Gershon AA, eds. Varicella-zoster virus, virology and clinical management. Cambridge, UK: Cambridge University Press;2000:246–275. References: 1. Straus SE, Oxman MN. Varicella and herpes zoster. 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, Pellissier JM, Saddier P, Nikas AA. The incidence of herpes zoster in a United States administrative database. J Gen Intern Med. 2005;20:748–753. 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. Clinical manifestations of herpes zoster. 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 Description ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is a lyophilized preparation of the Oka/Merck strain of live, attenuated VZV. Each 0.65-mL dose of the vaccine contains a minimum of 19,400 plaque-forming units (PFU) of attenuated virus.

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). Introducing ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] Before we discuss herpes zoster disease I would like to introduce ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)], which was approved by the FDA in May 2006. ZOSTAVAX is indicated for the prevention of herpes zoster (shingles) in individuals 60 years of age and older. ZOSTAVAX is not indicated for the treatment of zoster or postherpetic neuralgia. Overall, the benefit of ZOSTAVAX in the prevention of postherpetic neuralgia can be primarily attributed to the effect of the vaccine on the prevention of zoster.

44 Clinical Pharmacology: The Shingles Prevention Study Design
Subjects Enrolled N=38,546 Adverse Event (AE) Substudy n=6,616 Immunogenicity Substudy n=1,395 Clinical Pharmacology: The Shingles Prevention Study Design The Shingles Prevention Study was a placebo-controlled, randomized, double-blind study.1 The study enrolled a total of 38,546 subjects who were 60 years of age or older.1 Randomization was stratified by age1: 60 to 69 years of age ≥70 years of age Subjects were randomized to receive either a single dose of zoster vaccine (n=19,270) or placebo (n=19,276).1 The median follow-up of the study was 3.1 years (range 31 days to 4.9 years). The study excluded people who were immunocompromised or using corticosteroids on a regular basis, anyone with a previous history of zoster, and those with conditions that might interfere with study evaluations, including people with cognitive impairment, severe hearing loss, those who were non-ambulatory and those whose survival was not considered to be at least 5 years. The clinical trial included 2 substudies1: The Adverse Event (AE) Monitoring Substudy, which comprised 6,616 subjects. An immunogenicity substudy, which comprised 1,395 subjects. Zoster cases were confirmed by polymerase chain reaction (93%), viral culture (1%), or in the absence of viral detection, by the Clinical Evaluation Committee (6%). Individuals in both vaccination groups who developed zoster were given famciclovir and, as necessary, pain medications.1 Age ≥70 years n=17,799 Age 60 to 69 years n=20,747 Zoster vaccine n=10,378 Placebo n=10,369 Zoster vaccine n=8,892 Placebo n=8,907 Oxman MN, Levin MJ, Johnson GR, et al. N Engl J Med. 2005;352:2271–2284. Reference: 1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271–2284.

45 Patient Demographics in the Shingles Prevention Study
Characteristic Vaccine Group N=19,270 Placebo Group N=19,276 Age 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) Patient Demographics in the Shingles Prevention Study Baseline patient characteristics were similar in both vaccination groups in the Shingles Prevention Study.1 The age distribution of enrolled patients was 59 to 99 years in both groups. The gender distribution was 59% male and 41% female.1 The racial distribution of white (95%), black (2%), Hispanic (1%), and other (1%) was also similar in both groups.1 Oxman MN, Levin MJ, Johnson GR, et al. N Engl J Med. 2005;352:2271–2284. Reference: 1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271–2284.

46 Prevention of Herpes Zoster
–51% (95% CI: 44%, 58%) Placebo 700 HZV 600 642 500 –64% (95% CI: 56%, 71%) 400 Number of zoster cases –41% (95% CI: 28%, 52%) Prevention of Herpes Zoster ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] significantly reduced the risk of developing zoster compared with placebo*: 315/19,254 cases (5.4 cases per 1,000 person-years) vs 642/19,247 cases (11.1 cases per 1,000 person-years). The protective efficacy was 51% (95% CI: 44%, 58%).1 Vaccine efficacy for the prevention of zoster was highest for those subjects 60 to 69 years of age and declined with increasing age. ZOSTAVAX reduced the incidence of zoster by 64% in individuals 60 to 69 years of age (ZOSTAVAX, n=10,370; placebo, n=10,356); by 41% in individuals 70 to 79 years of age (ZOSTAVAX, n=7,621; placebo, n=7,559); and by 18% in individuals 80 years of age or older (ZOSTAVAX, n=1,263; placebo, n=1,332). As with any vaccine, vaccination with ZOSTAVAX may not result in protection of all vaccine recipients. The duration of protection after vaccination with ZOSTAVAX is unknown. In the Shingles Prevention Study, protection from zoster was demonstrated through 4 years of follow-up. The need for revaccination has not been defined. *Primary analysis was performed on the modified intent-to-treat (MITT) population that included all randomized patients who were followed for at least 30 days postvaccination and did not develop an evaluable case of zoster within the first 30 days postvaccination. 300 334 315 261 200 –18% (95% CI: –29%, 48%) 100 156 122 47 37 11.1 5.4 10.8 3.9 11.4 6.7 12.2 9.9 Incidence rate of zoster per 1,000 person-years Overall 60–69 70–79 ≥80 Age (years) Reference: 1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271–2284.

47 Postherpetic Neuralgia* in the Shingles Prevention Study
50 Placebo HZV 40 –26% (95% CI: –69%, 68%) 30 % of Zoster Cases with Postherpetic Neuralgia –55% (95% CI: 18%, 76%) –39%† (95% CI: 7%, 59%) 25.5 20 Postherpetic Neuralgia in the Shingles Prevention Study Postherpetic neuralgia was defined as zoster-associated pain (rated as ≥3 on a 10-point scale by the patient) occurring or persisting at least 90 days following the onset of rash in evaluable cases of zoster. Overall, the benefit of ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] in the prevention of postherpetic neuralgia can be primarily attributed to the effect of the vaccine on the prevention of zoster. Vaccination with ZOSTAVAX reduced the incidence of postherpetic neuralgia in individuals 70 years of age and older who developed zoster postvaccination. Following completion of the Shingles Prevention Study, a separate analysis was conducted to evaluate the reduction in postherpetic neuralgia in the group of individuals who have been vaccinated with ZOSTAVAX, but who had developed zoster. In the analysis, the overall efficacy of ZOSTAVAX for reduction of postherpetic neuralgia in patients who developed zoster following vaccination was 39% (95% CI: 7%, 59%). This is an age-adjusted estimate calculated based on the age strata of 60 to 69 and 70 years of age and older at randomization. The vaccine efficacy against postherpetic neuralgia in patients who developed zoster following vaccination was 5% (95% CI: –107%, 56%) in patients 60 to 69 years of age; 55% (95% CI: 18%, 76%) in patients 70 to 79 years of age: and 26% (95% CI: –69%, 68%) in patients 80 years of age and older. 18.9 –5% (95% CI: –107%, 56%) 17.2 10 12.5 8.6 6.9 6.6 7.7 Number of PHN Cases 80 27 23 8 45 12 12 7 Number of HZ Cases 642 315 334 122 261 156 47 37 Overall 60–69 70–79 ≥80 Age (years) *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.

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 Herpes Zoster Vaccine (N = 19,270)
Specific Complications* of Zoster Among Zoster Cases in the Shingles Prevention Study Complication Herpes Zoster Vaccine (N = 19,270) Placebo (N = 19,276) ( n = 321) % Among Zoster Cases (n = 659) 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) 12 1.8 Ptosis Scarring 24 7.5 57 8.6 Sensory Loss 2.2 Specific Complications of Zoster Among Zoster Cases in the Shingles Prevention Study The table shows the number of patients with specific complications of zoster among zoster cases that were reported in the Shingles Prevention Study at a frequency of ≥1% in at least one vaccination group among subjects with zoster. The number of zoster cases included the cases that developed within 30 days after vaccination. Prespecified zoster-related complications were reported less frequently in subjects who received ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] compared with subjects who received placebo. Among zoster cases, zoster-related complications were reported at similar rates in both vaccination groups. Visceral complications reported by fewer than 1% of subjects with zoster included 3 cases of pneumonitis and 1 case of hepatitis in the placebo group, and 1 case of meningoencephalitis in the vaccine group. N=number of subjects randomized n=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 Adverse Reactions Overall, ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] has been evaluated in approximately 21,000 adults. In the Shingles Prevention Study, patients were given either a single dose of the zoster vaccine (n=19,270) or placebo (n=19,276). 15,925 subjects who received ZOSTAVAX and 16,005 subjects who received placebo, were actively followed for safety outcomes through Day 42 postvaccination. Patients were followed passively for safety after Day 42 postvaccination to the end of the study. Patients enrolled in the AE Monitoring substudy (3,345 who received ZOSTAVAX and 3,271 who received placebo) used vaccination report cards to record AEs during the 42-day postvaccination period. Monthly surveillance for hospitalization was conducted through the end of the study, 2 to 5 years postvaccination. 97% of patients in both vaccination groups completed the vaccination report cards.

53 Relative Risk (RR) (95% CI)
Number of Subjects With ≥1 Serious Adverse Experience (0–42 Days Postvaccination) in the Shingles Prevention Study Cohort HZV n/N % Placebo n/N % Relative Risk (RR) (95% CI) Overall Study Cohort (all ages) 255/18, % 254/18, % 1.01 (0.85, 1.20) 60–69 years old 113/10, % 101/10, % 1.12 (0.86, 1.46) 70–79 years old 115/7, % 132/7, % 0.87 (0.68, 1.11) ≥80 years old 27/1, % 21/1, % 1.36 (0.78, 2.37) AE Monitoring Substudy Cohort (all ages) 64/3, 41/3, 1.53 (1.04, 2.25) 22/1, % 18/1, % 1.21 (0.66, 2.23) 31/1, % 19/1, % 1.61 (0.92, 2.82) 11/ % 4/ % 2.19 (0.75, 6.45) Number of Subjects With ≥1 Serious Adverse Experience (0-42 Days Postvaccination) in the Shingles Prevention Study In the overall study population, SAEs occurred at a similar rate of 1.4% in patients who received either ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] or placebo (relative risk [RR]: 1.01). In the AE Monitoring Substudy, the rate of SAEs was increased in the group that received ZOSTAVAX compared to the placebo group (1.9% vs 1.3%, respectively; RR: 1.53). N = number of subjects in cohort with safety follow-up n = number of subjects reporting an SAE 0–42 days postvaccination

54 AE Monitoring Substudy
Selected Serious Adverse Experiences (SAE) Reported More Frequently After HZV than After Placebo Days 0–42 Postvaccination in the Shingles Prevention Study AE Monitoring Substudy Entire Study Cohort HZV N = 3,326 Placebo N = 3,249 HZV N = 18,671 N = 18,717 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) Selected Serious Adverse Experiences (SAE) Reported More Frequently After ZOSTAVAX than After Placebo Days 0–42 Postvaccination in the Shingles Prevention Study This table displays selected cardiovascular SAEs occurring in the SPS within 42 days postvaccination. For the entire Shingles Prevention Study population, the rates of overall cardiovascular events (0.4%), including coronary artery disease-related conditions (0.2%), were similar in subjects vaccinated with ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] or placebo. In the AE Monitoring Substudy of the Shingles Prevention Study, between Days 0 to 42 postvaccination, the rate of overall cardiovascular events was higher after ZOSTAVAX (0.6%) than after placebo (0.4%), including the rate of coronary artery disease-related conditions postvaccination (ZOSTAVAX 0.3%, placebo 0.2%). N=number of subjects with safety follow-up n=number of subjects reporting SAE within the category *CAD-related conditions: angina pectoris, coronary artery disease, coronary occlusion, cardiovascular disorder, myocardial ischemia, & myocardial infarction

55 Injection-Site and Systemic Adverse Experiences
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 Adverse Experience HZV (n = 3,345) % Placebo (n = 3,271) Injection Site Erythema* Pain/tenderness* Swelling* Hematoma Pruritus Warmth 33.7 33.4 24.9 1.4 6.6 1.5 6.4 8.3 4.3 1.0 0.3 Systemic Headache 0.8 Injection-Site and Systemic Adverse Experiences Vaccine-related injection-site reactions and systemic AEs reported at an incidence of 1% or greater in the AE Monitoring Substudy are shown in the table. Most of these AEs were reported as mild in intensity. The overall incidence of vaccine-related injection-site reactions was significantly greater in subjects who received ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] (48%) compared with those who received placebo (17%). The numbers of patients with elevated temperature (38.3oC [101.0oF]) within 42 days postvaccination were similar in the ZOSTAVAX and the placebo groups (0.8% vs 0.9%, respectively). *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. Adverse Events Occurring After Day 42 Postvaccination This slide shows adverse events occurring after Day 42 postvaccination through the end of the study, a total of 4.9 years.

57 Summary: ACIP Rationale for Zoster Vaccine Recommendations
Zoster causes substantial morbidity in US: 1 million cases per year, with risk of severe complications Antiviral therapy only partially effective and time dependent. Therapy for PHN inadequate for many HZV appears cost effective by usual comparison Vaccine efficacious, based on reduction in incidence of zoster (51%), PHN (65%), and overall burden of illness (61%) Efficacy, though somewhat reduced, is still present even in oldest age groups

58 ACIP Recommendations for Use of HZV
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. 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. 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 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 ?

61 Clinical Management Case 1
The major reason given by patients as to why they do not receive recommended vaccines is: Failure to receive a physician recommendation Fear of needles Concern about costs Worries about side effects Need correct answer

62 Clinical Management Case 2
Reasons for deferring immunization with Herpes Zoster Vaccine in a 68 yo African American female include: A prior history of shingles Current treatment with chemotherapy for breast cancer Symptoms of a cold with temperature of F. All of the above Need correct answer

63 Contraindications to HZV
Anaphylactic reaction hx to any component (usually neomycin or gelatin) 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. Selected Precautions (cont) 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. The risk of transmitting the attenuated vaccine virus to a susceptible individual should be weighed against the risk of developing natural zoster that could be transmitted to a susceptible individual. 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). Conditions for Storage ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] should be stored 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 for storing ZOSTAVAX. The diluent should be stored 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. Dosage and Administration ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is for subcutaneous administration only; do not inject intravascularly. Individuals should receive a single dose. Reconstitute immediately upon removal from freezer. To reconstitute, first withdraw the entire contents of the diluent vial into a syringe. Inject all of the diluent in the syringe into the vial of lyophilized vaccine and gently agitate to mix thoroughly. Withdraw entire contents of reconstituted vaccine into a syringe and inject the total volume subcutaneously, preferably into upper arm. The vaccine should be administered immediately after reconstitution, to minimize loss of potency. Discard reconstituted vaccine if not used within 30 minutes. Do not freeze the reconstituted vaccine.

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 Physician Barriers to Vaccination1 Physicians who administered adult vaccinations responded to a mailed survey that queried their practices, policies, and attitudes regarding adult vaccination. Patient concern about vaccine safety was cited as a major barrier. Practical barriers included domination of the office visit by urgent medical concerns and lack of knowledge of the patients’ vaccination history. Educational issues cited were the need for clearer vaccination guidelines and the lack of patient-oriented information about vaccines. Inadequate reimbursement for vaccines was also considered an issue. Key Point: Physicians may have various reasons for not offering adult vaccinations in their practices. Szilagyi PG, Shone LP, Barth R, et al. Prev Med. 2005;40:152–161. Reference: 1. Szilagyi PG, Shone LP, Barth R, et al. Physician practices and attitudes regarding adult immunizations. 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 Patient Barriers to Vaccination There are many reasons why adult vaccination has not been as successful as the childhood vaccination program. One of the reasons is related to patients’ beliefs and attitudes about vaccination. The 1996 Medicare Current Beneficiary Survey, an ongoing, nationally representative longitudinal survey of approximately 16,000 Medicare beneficiaries, queried participants who were 65 years of age and older as to why they had not been vaccinated for influenza and pneumococcal disease.1 Not knowing that vaccination was needed was the most common reason cited for not receiving the vaccines. In addition, according to a separate CDC publication, some adults think that vaccines they received as children offer lifelong protection. Although this may be true for many vaccines, adults may not have received all necessary vaccines, some vaccines may not have been available at the time, and immunity to some vaccines may wane over time.2 Key Point: Adult patients may have various reasons for not getting vaccinated. Centers for Disease Control and Prevention. MMWR. 1999;48:886–890. References: 1. Centers for Disease Control and Prevention. Reasons reported by Medicare beneficiaries for not receiving influenza and pneumococcal vaccinations―United States, MMWR. 1999;48:886–890. 2. Centers for Disease Control and Prevention. Adult immunization schedule. Available at: Accessed June 6, 2006.

73

74 Screening Questionnaire for Adult Immunization
Yes No Don’t know □ □ □ 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? Screening Questionnaire for Adult Immunization1 To assist in the decision-making process regarding appropriate vaccinations and possible contraindications to vaccination, patients should be asked about their vaccination history as well as other factors that might influence the decision. An example of a questionnaire that might be used for this purpose is shown on this slide. This questionnaire was adapted from one developed by the Immunization Action Coalition. Key Point: There are tools available to help identify appropriate candidates for vaccination. Adapted from the Immunization Action Coalition. Available at: Reference: 1. Immunization Action Coalition. Screening questionnaire for adult immunization. Available at: Accessed February 26, 2007.

75 Standards for Adult Immunization Practices
Make vaccinations available Identify and minimize barriers Assess patients’ vaccination status Communicate 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 Standards for Adult Immunization Practices1 The Standards for Adult Immunization Practices were first developed in 1990 as a large collaborative effort led by the National Vaccine Advisory Committee (NVAC) to encourage best practices. They have recently been revised to reflect major changes in the healthcare system during the last decade. Primary care healthcare professionals are encouraged to include vaccinations as part of their routine care of adults. Barriers such as physical examinations or extra visits to administer vaccines should be minimized. The patient’s vaccination status can be ascertained by reviewing vaccination history as well as assessing medical and lifestyle risk factors, occupation, and potential contraindications to vaccination. The healthcare professional should discuss with the patient the risks and benefits of vaccination and the diseases vaccinations prevent and should provide educational material if available. Office protocols help define appropriate procedures for administering vaccines. Office personnel should be properly trained to manage vaccination procedures and should be vaccinated as recommended. Strategies to improve vaccination rates might include reminder/recall systems. Vaccination providers can work with other healthcare professionals and the community to help meet the needs of the population served. Key Point: Standards to help achieve best adult immunization practices have been defined. 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. Reference: 1. Poland GA, Shefer AM, McCauley M, Webster PS, Whitley-Williams PN, Peter G, and the National Vaccine Advisory Committee. Standards for adult immunization practices. Am J Prev Med. 2003;25:144–150.

76 Clinical Practice Recommendation
Zoster vaccine is recommended for all adults age 60 and above. Evidence-Based Source: National Guidelines Clearinghouse Web Site of Supporting Evidence: 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

77 Clinical 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: 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

78 Post-Test Questions

79 ?

80 More than 90% of US adults are susceptible to zoster.
Which of the following is/are true statements? Herpes zoster results from the reactivation of the varicella-zoster virus (VZV). More than 90% of US adults are susceptible to zoster. Estimated 1 million cases per year in the United States. Incidence and severity of zoster increase with advancing age. All of the above Answer: 5 – all of the above; ARS tech: display results from pre and post test questions and correct answer

81 Direct fluorescent antibody (DFA) Tzanck prep Wright stain
The preferred rapid test for distinguishing between H. simplex and H. zoster is: Viral culture Direct fluorescent antibody (DFA) Tzanck prep Wright stain None of the above Need answer; ars tech: display results from pre and post test question and correct answer

82 Which of the following reasons is/are valid for recommending against use of Herpes Zoster Vaccine?
History of anaphylaxis to neomycin Daily use of 5 mg Prednisone Insulin-requiring diabetes mellitus All of the above Answer: 4 – all of the above; ars tech: display results from pre and post test question and correct answer

83 You see a 64 year old man with a diagnosis of melanoma, currently on a course of chemotherapy. Which of the following is a valid reason for deferring herpes zoster vaccine in this situation? A prior history of shingles Current chemotherapy Symptoms of a cold with temperature of F. All of the above None of the above Answer: 2 – chemotherapy; ars tech: display results from pre and post test question and correct answer

84 You are advising one of your patients about receiving herpes zoster vaccine. She has several grandchildren and a pregnant daughter. Which of the following is a true statement concerning risk of transmission after vaccination? Transmission of the vaccine virus has been reported in clinical trials. There is a theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox. There is no risk of transmitting the attenuated vaccine virus to a susceptible individual. None of the above Answer: 2 - There is a theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.; ars tech: display results from pre and post test questions and correct answer


Download ppt "Understanding Herpes Zoster & the Critical Importance of Herpes Zoster Vaccine W. Paul McKinney, MD University of Louisville Welcome to this Merck."

Similar presentations


Ads by Google