ABC of HERPES ZOSTER Disease burden Epidemiology, Clinical & Psychological Impact & Prevention DR. SHARDA JAIN Sec. Gen. D.G.F.

1. DELHI GYANAECOLOGIST FORUM DRIVE
FOR Adult women vaccination
DR. SHARDA JAIN
Sec. Gen. D.G.F.
ABC of HERPES ZOSTER
Disease burden
Epidemiology, Clinical & Psychological Impact
& Prevention

2. DELHI GYNAECOLOGIST FORUM HAS STARTED ITS
ACCOUNT in slideshare.net
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Preventing the preventable… DGF Series

3. Varicella is the Primary Infection Caused by
Varicella-Zoster Virus1
Varicella
(Chickenpox) CDC Public Health Image Library (ID#1878).
Credit: CDC/PHIL, Dr. Erskine Palmer, B.G. Partin0
Varicella-Zoster Virus (VZV)
Primary Disease
1. Weaver BA. J Am Osteopath Assoc. 2009;109(suppl 2):S2–S6.
2. Gershon AA et al. Clin Microbiol Rev. 2013;26:728–743.
Child image courtesy of: Weaver BA. Herpes zoster overview: natural history and incidence.
J Am Osteopath Assoc. 2009;109(suppl 2):S2–S6. Reprinted with permission.

4. Most Adults Worldwide Are Seropositive
For VZV by Age 40 Years
0
20
40
60
80
100
0–4 5–9 10–14 15–19 20–29 30–39 40–49 >50
Argentina1 Australia2
Brazil3 Canada4
Italy5 Malaysia6
Mexico7 Netherlands8
Philippines6 South Korea9
Thailand10 Turkey11
UK12 US13
Seroprevalence of VZV by Age1–13
Age (years)
Seroprevalence(%)
Argentina1
Brazil3
Italy5
Mexico7
Philippines6
Thailand10
UK12
Australia2
Canada4
Malaysia6
Netherlands8
South Korea9
Turkey11
US13
VZV=varicella-zoster virus.
1. Dayan GH et al. J Clin Microbiol. 2004;42:5698–5704. 2. O’Grady KA et al. Trop Med Int Health. 2000;5:732–736. 3. Lafer MM et al. Rev Inst Med Trop Sao
Paulo. 2005;47:139–142. 4. Brisson M et al. Epidemiol Infect. 2001;127:305–314. 5. Gabutti G et al. BMC Public Health. 2008;8:372. 6. Lee BW. Trop Med Int
Health. 1998;3:886–890. 7. Conde-Glez C et al. Vaccine. 2013;31:5067–5074. 8. van Lier A et al. Vaccine. 2013;31:5127–5133. 9. Lee H et al. J Korean Med Sci.
2013;28:195–199. 10. Migasena S et al. Int J Infect Dis. 1997;2:26–30. 11. Koturoglu G et al. Paediatr Perinat Epidemiol. 2011;25:388–393. 12. Kudesia G et al. J
Clin Pathol. 2002;55:154–155. 13. Kilgore PE et al. J Med Virol. 2003;70 Suppl 1:S111–S118.

5. Varicella-Zoster Virus Establishes Latency
During Primary Infection1,2
VZV=varicella-zoster virus.
1. Weinberg A et al. Curr Top Microbiol Immunol. 2010;342:341–357. 2. Gershon AA et al. Clin Microbiol Rev. 2013;26:728–743.
Child image courtesy of: Weaver BA. Herpes zoster overview: natural history and incidence. J Am Osteopath Assoc.
2009;109(suppl 2):S2–S6. Reprinted with permission.
Spinal image adapted from Johnson RW, Herpes zoster and postherpetic neuralgia, Expert Review of Vaccines, Vol. 9,
supplement 3, copyright © 2010, Informa Healthcare. Reproduced with permission of Informa Healthcare.
Dorsal root
ganglion
VZV establishes
latency in the
dorsal root ganglion
VZV moves along
the sensory nerve to the
dorsal root ganglion
Varicella rash
Skin
Spinal cord
Varicella
(Chickenpox)

6. Latent Varicella-Zoster Virus Reactivates
to Cause Herpes Zoster1,2
VZV=varicella-zoster virus.
1. Schmader K et al. J Infect Dis. 2008;197 Suppl 2:S207–S215.
2. Gershon AA et al. Clin Microbiol Rev. 2013;26:728–743.
Adult image courtesy of: Weaver BA. Herpes zoster overview: natural history and incidence. J Am
Osteopath Assoc. 2009;109(suppl 2):S2–S6. Reprinted with permission.
Spinal image adapted from Johnson RW, Herpes zoster and postherpetic neuralgia, Expert Review
of Vaccines, Vol. 9, supplement 3, copyright © 2010, Informa Healthcare. Reproduced with
permission of Informa Healthcare.
Dorsal root
ganglion
Herpes
zoster
rash
Skin
Spinal cord
Herpes Zoster
(Shingles)
Latent VZV reactivates in the
dorsal root ganglion,
causing intense inflammation
and necrosis of nerve cells
VZV moves along
the sensory nerve from the
dorsal root ganglion to the
skin

7. Reactivation of Latent VZV is Related to a
Decrease in Host Cell-Mediated Immunity1
VZV=varicella-zoster virus.
1. Arvin A. N Engl J Med. 2005;352(22):2266–2267.
Image from N Engl J Med, Arvin A, Aging, immunity, and the varicella-zoster virus,
Vol 352, p 2266-2267, © 2005 Massachusetts Medical Society. Reprinted with
permission from Massachusetts Medical Society.
VZVMemoryTCells
Age
Varicella infection Herpes zoster
Herpes
zoster
threshold
Exogenous
varicella
exposure
Silent
reactivation?

8. Older Age is Associated With Greater Risk
of Developing HZ (Worldwide)
HZ=herpes zoster.
1. Stein AN et al. Vaccine. 2009;27:520–529. 2. Tanuseputro P et al. Vaccine. 2011;29:8580–8584. 3. Gonzalez Chiappe S et al. Vaccine. 2010;28:7933–7938. 4. Weitzman D et al. J
Infect. 2013;67:463–469. 5. Gialloreti LE et al. BMC Infect Dis. 2010;10:230. 6. Toyama N et al. J Med Virol. 2009;81:2053–2058. 7. Ultsch B et al. Eur J Health Econ. 2013;14:1015–
1026. 8. de Melker H et al. Vaccine. 2006;24:3946–3952. 9. Esteban-Vasallo MD et al. J Infect. 2014;68:378–386. 10. Lin YH et al. Vaccine. 2010;28:1217–1220. 11. Gauthier A et al.
Epidemiol Infect. 2009;137:38–47.
12. Yawn BP et al. Neurology. 2013;81:928–930.
0
5
10
15
0 10 20 30 40 50 60 70 80
Australia1 Canada2 France3
Israel4 Italy5 Japan6
Germany7 Netherlands8 Spain9
Taiwan10 UK11 US12
Worldwide HZ Incidence by Age1–12
Age (years)
AnnualIncidence
(per1,000person-years)
Australia1
Israel4
Germany7
Taiwan10
Canada2
Italy5
Netherlands8
UK11
France3
Japan6
Spain9
US12

9. 1. Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat (2013).
World Population Prospects: The 2012 Revision. New York: United Nations.
esa.un.org/unpd/wpp/Documentation/pdf/WPP2012_Volume-I_Comprehensive-Tables.pdf. Accessed March 4, 2014.
35.5%
13.7%
23.3%
25.9%
23.1%
24.9%
18.3%
30.2%
23.8%
28.9%
25.2%
15.8%
6.4%
9.3%
9.5%
8.5%
12.5%
8.3%
10.5%
9.5%
11.2%
15.1%
0.0
Singapore
Philippines
Peru
Mexico
Malaysia
Korea
India
Costa Rica
Columbia
Brazil
Argentina
Percentage of Adults Aged ≥60 Years
(Latin America and Asia Pacific)
2013
2050
The Age Group at Greatest Risk for
Herpes Zoster is Growing Worldwide (continued)1

10. Clinical Manifestations and
Complications of Herpes Zoster

11. Clinical Presentation of Herpes Zoster
aReview of pain assessment tools and index scores from multiple studies of diverse acute and chronic pain conditions.
1. Johnson RW. Herpes. 2007;14(suppl 2):30A–34A. 2. Harpaz R et al. MMWR Recomm Rep. 2008;57(RR-5):1–30.
3. Drolet M et al. Hum Vaccin Immunother. 2013;9:1177–1184. 4. Katz J et al. Surg Clin North Am. 1999;79:231–252.
Graphic reprinted with author permission (RW Johnson, r.w.johnson@bris.ac.uk).
Prodromal Pain Acute Pain
Subacute
Herpetic Neuralgia
Chronic Pain: Postherpetic Neuralgia (PHN)
Acute Phase1,2 Chronic Phase1
Day 0 2–4 Weeks 3 Months Months/Years
Rash HealedRash Onset
Patients have compared the severity of herpes zoster pain to
other pain conditions, including:
Prodromal pain3
• Angina
• Kidney stones
Acute pain4,a
• Labor pain
• Postsurgical pain
Chronic pain (PHN)4,a
• Arthritis
• Fibromyalgia

12. Herpes Zoster Rash Follows a
Dermatomal Distribution1,2
C=cervical; L=lumbar; S=sacral; T=thoracic; V (roman numeral 5)=trigeminal (5th) cranial nerve.
1. Cohen JI. N Engl J Med. 2013;369:255–263. 2. Seward J et al. In: Arvin A et al, eds. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis.
Cambridge, UK: Cambridge University Press; 2007. Chapter 40. ncbi.nlm.nih.gov/books/NBK47367/. Accessed March 10, 2014.
V1
V3
V2
© Bart’s Medical Library / Phototake.
© Dr. P. Marazzi / Science Source
© Dr. Allan Harris / Phototake.
Netter illustration from www.netterimages.com. © Elsevier Inc. All
rights reserved
Trigeminal ~13%
Cervical ~14%
Thoracic ~50%
Lumbar ~13%

13. Degree of Pain in Herpes Zoster1
Katz J & Melzack R. Measurement of Pain. Surgical Clinics North America. 1999;;79(2):231-252.
Chronic pain
conditions
Mild pain
Severe pain
Abdominal
hysterectomy
Acute headache
Herpes zoster
Labor pain
Post-surgical pain
Mucositis
Angioplasty
sheath removal
Post-herpetic neuralgia
Chronic cancer pain
Fibromyalgia
Rheumatoid arthritis
Arthritis/osteoarthritis
Musculoskeletal pain
Atypical facial pain
Adapted from Katz J & Melzack R.
*SF-MPQ : Short-Form McGill Pain Questionnaire
Acute pain
conditions
0
10
20
30

14. Herpes Zoster Can Affect Almost Anyone
• Herpes zoster may occur in any person with a
history of varicella. There is no way to predict
– WHEN the varicella-zoster virus will reactivate1,2
– WHO will develop herpes zoster1,2
– HOW SEVERE an individual case may be1,3
– HOW LONG the pain will last1,2
1. Harpaz R et al. MMWR. 2008;57(RR-5):1–30.
2. Weaver BA. J Am Osteopath Assoc. 2009;109(suppl 2):S2–S6.
3. Oxman MN. J Am Osteopath Assoc. 2009;109(suppl 2):S13–S17.

15. Potential Complications of Herpes Zoster
Neurologic1,2
• Postherpetic neuralgia
• Cranial and motor neuron
palsies
– Ramsey Hunt
syndrome
– Bell’s palsy
• Encephalitis
• Stroke
• Hearing loss
© Ingram Publishing/the Agency Collection/Getty Images
© alexluengo, iStockphoto
© Ingram Publishing/the Agency Collection/Getty Images
© MedicalRF.com/Getty Images
1. Drolet M et al. Hum Vaccin Immunother. 2013;9:1177–1184.
2. Harpaz R et al. MMWR Recomm Rep. 2008;57(RR-5):1–30.
3. Oxman MN. Varicella-Zoster Virus: Virology and Clinical Management. Cambridge University Press;
2000:246–275.
Cutaneous2,3
• Bacterial superinfection
• Scarring
Visceral (rare)3
• Myocarditis
• Pericarditis
• Arthritis
• Hepatitis
Ophthalmic2,3
• Visual loss
• Pain
• Facial scarring
• Keratitis

16. POSTHERPETIC NEURALGIA (PHN)
• PHN is the most common complication of HZ1
• The prevalence of PHN varies greatly, depending on
the definition used1
– Pain beyond 30 days: 30% in people younger than 40 and
up to 74% in those 60 years and older
– Pain beyond 90 days: 6% in people younger than 40 and
12% in those 60 years and older
• Risk factors for PHN include advanced age, female
sex, presence of a prodrome, greater rash severity,
and greater acute pain severity1,2
HZ=herpes zoster.
1. O'Connor KM et al. Med Clin North Am. 2013;97:503–522.
2. Johnson RW. Herpes. 2007;14(suppl 2):30A–34A.

17. Herpes Zoster Ophthalmicus May Result
in Other Serious Complications1
1. Pavan-Langston D. In: Arvin AM et al, eds. Varicella-Zoster Virus: Virology and Clinical Management. Cambridge
University Press; 2000:276–298. Pavan-Langston D, Ophthalmic zoster, In: Arvin AM, Gershon AA, eds, Varicella-Zoster
Virus: Virology and Clinical Management, 276–298, © 2000 Cambridge University Press. Reprinted with permission.0
Acute Herpes Zoster Ophthalmicus 2 months Post Acute
Herpes Zoster Ophthalmicus

18. HZ and PHN Impact 4 Health Domains1
HZ=herpes zoster; PHN=postherpetic neuralgia.
1. Johnson RW et al. BMC Medicine. 2010;8:37–49.
Physical
 Fatigue
 Anorexia
 Weight loss
 Reduced mobility
 Physical inactivity
 Insomnia
Psychological
 Depression
 Anxiety
 Emotional distress
 Difficulty concentrating
 Fear
Social
 Withdrawal
 Isolation
 Attendance at fewer social
gatherings
 Loss of independence
 Change in social role
Functional
 Dressing, bathing
 Housework
 Eating, cooking
 Mobility
 Traveling
 Shopping
HZ=herpes zoster; PHN=postherpetic neuralgia.
1. Johnson RW et al. BMC Medicine. 2010;8:37–49.
Physical
 Fatigue
 Anorexia
 Weight loss
 Reduced mobility
 Physical inactivity
 Insomnia
Psychological
 Depression
 Anxiety
 Emotional distress
 Difficulty concentrating
 Fear
Social
 Withdrawal
 Isolation
 Attendance at fewer social
gatherings
 Loss of independence
 Change in social role
Functional
 Dressing, bathing
 Housework
 Eating, cooking
 Mobility
 Traveling
 Shopping

19. WHAT ABOUT THE TREATMENT OPTIONS?
HZ=herpes zoster; PHN=postherpetic neuralgia.

20. Treating Herpes Zoster and PHN
Can Be Difficult
• Treatment for HZ and PHN often requires a multifaceted approach1–3
HZ=herpes zoster; PHN=postherpetic neuralgia.
1. Cohen JI. N Engl J Med. 2013;369:255–263. 2. Johnson RW. J Infect Dis. 2002;186(Suppl 1):S83–S90. 3. Harpaz R et al. MMWR. 2008;57(RR-5):1–30. 4. Chen N et al. Cochrane Database Syst
Rev. 2014 Feb 6;2:CD006866. doi: 10.1002/14651858.CD006866.pub3. 5. Sacks GM. Am J Manag Care. 2013;19(1 Suppl):S3–S9. 6. Glauser TA et al. J Pain Res. 2011;4:407–415.
HZ PHN
Non-narcotic
analgesics
Antivirals
Narcotic
analgesics
Anticonvulsants
for pain
management
Topical
agents
Corticosteroids
• Antiviral therapy for acute HZ should be initiated within 72 hours of
appearance of skin lesions1–3
– Antiviral therapy hastens the resolution of skin lesions but does not significantly
reduce the incidence of PHN1,4
• PHN is often refractory to treatment and treatment satisfaction is poor
– Patients often report intolerable treatment-related side effects with therapeutic
agents for PHN5

21. Treatment Considerations For Older Adults
• Many older adults have comorbidities and are taking medications
that may complicate treatment of HZ and PHN1–3
• Management of HZ and PHN in vulnerable and frail elderly
patients requires modified pharmacotherapeutic approaches and
augmented nonpharmacotherapeutic approaches3
– Available treatment options may require several weeks to reach target
dosing, during which time patients have inadequate pain control2
• Patients should be monitored for inadequate
response to treatment and functional decline3
HZ=herpes zoster; PHN=postherpetic neuralgia.
1. Harpaz R et al. MMWR. 2008;57(RR-5):1–30.
2. Sacks GM. Am J Manag Care. 2013;19(1 Suppl):S3–S9.
3. Dworkin RH et al. Clin Infect Dis. 2007;44(1 Suppl):S1–26.
Comorbidities
Poly-
pharmacy
Drug-drug
interactions
Adverse
effects

22. TAKE HOME MESSAGES
of Herpes Zoster disease
• Herpes zoster (HZ) is caused by reactivation of latent
varicella-zoster virus in dorsal root and cranial sensory
ganglia
• HZ causes pain and suffering for millions of people
worldwide each year
• There is no way to predict
– When the varicella-zoster virus will reactivate
– Who will develop HZ
– How severe an individual case may be
– How long the pain will last
• Almost all adults aged ≥50 years are at risk for this
often debilitating disease, with risk increasing with age

23. TAKE HOME MESSAGES
• Postherpetic neuralgia (PHN) is the most common
complication of herpes zoster
• PHN can be difficult to manage and refractory to
treatment and can persist for months or even years
• PHN and other less common complications can
cause prolonged disability, substantially reduce
quality of life, and interfere with activities of daily
living
– Herpes zoster and its complications can be a psychosocial and economic
burden to individuals,
their families, and society

24. About ZOSTAVAX™
[Zoster Vaccine LIVE (Oka/Merck)]

25. ZOSTAVAX™ [ZOSTER VACCINE LIVE
(OKA/MERCK)] PRODUCT PROFILE
• Live, attenuated VZV vaccine
• Minimum of 19,400 PFU per dose1
– 14 times the minimum potency of VARIVAX™
[Varicella Virus Vaccine Live (Oka/Merck)]
• No preservative
• Lyophilized product
• Single subcutaneous dose
PFU=plaque-forming unit; VZV=varicella-zoster virus.
1. Oxman MN et al. N Engl J Med. 2005;352:2271–2284.

26. ZOSTAVAX™ [Zoster Vaccine Live (Oka/Merck)]
Indications and Contraindications
• ZOSTAVAX is indicated for vaccination of adults
aged 50 years and older for
– Prevention of herpes zoster (HZ)
– Prevention of postherpetic neuralgia (PHN)
– Reduction of acute and chronic HZ-associated pain
• History of anaphylactic/anaphylactoid reaction to
gelatin, neomycin, or any other component of the
vaccine
• Immunosuppression or immunodeficiency
• Active untreated tuberculosis
• Pregnancy
Indications
Contra-
indications

27. Recommendations for
Zoster Vaccination

28. International Recommendations for
ZOSTAVAX™ [Zoster Vaccine Live (Oka/Merck)]
CDC=Centers for Disease Control and Prevention.
Please see Speaker Notes for reference list.
United States CDC Advisory Committee on Immunization Practices:
adults aged ≥60 years
Canada National Advisory Committee on Immunization:
adults aged ≥60 years, may be used in adults aged 50–59 years
Europe • UK: Joint Committee on Vaccines and Immunisation:
adults aged 70–79 years, and catch-up for adults aged 79 years
• Austria: Empfehlungen des Obersten Sanitätsrates:
adults aged ≥50 years
• France: Haut Conseil de la Santé Publique:
adults aged 65–74 years, and catch-up for adults aged 75–79 years
• Greece: National Vaccine Committee: adults aged ≥60 years
• Sweden: Dental and Pharmaceutical Benefits Agency (TLV):
reimbursement for adults aged ≥50 years

29. API recommendations on Adult
Immunization 2014
D, S., & V, R. (2015). Adult Immunization 2014 (2nd ed., p. 251). New Delhi: Jaypee brothers medical publishers (P) Ltd.

30. SUMMARY
• ZOSTAVAX™ [Zoster Vaccine Live (Oka/Merck)] is administered in a
single dose to adults over 50 or over 60 years of age—starting age
depends on guidance by local public health agencies
• ZOSTAVAX was shown to boost varicella-zoster virus (VZV)–specific
cellular immunity, which is thought to be the mechanism by which it
protects against herpes zoster and its complications
• In clinical trials, ZOSTAVAX reduced the incidence, severity, and
complications of herpes zoster
• In clinical trials, ZOSTAVAX had a demonstrated safety and tolerability
profile, with adverse events largely limited to injection-site reactions

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