1. Varicella (Chickenpox) and Herpes Zoster (Shingles)
Jennifer Zipprich Immunization Branch California Department of Public Health October 17th, 2012

2. Varicella-Zoster Virus (VZV)
Human alpha-herpesvirus
Causes varicella (chickenpox) and herpes zoster (shingles)
Primary VZV infection leads to chicken pox
VZV establishes latency in dorsal root ganglia after primary infection
VZV can reactivate at a later time, causing herpes zoster
There are 3 licensed vaccines to prevent varicella (Varivax®, Proquad®) and herpes zoster (Zostavax®) in the US:
Varivax® (licensed 1995)
Proquad® (licensed 2005)
Zostavax® (licensed 2006)
Note: place CDC logo on all slides except #1 – Title slide 2

3. Varicella Clinical Features
Incubation period days (range days)
Mild prodrome for 1-2 days
Rash generally appears first on head; most concentrated on trunk
Successive crops over several days with lesions present in several stages of development

4. Breakthrough Varicella
Breakthrough varicella is defined as infection with wild-type varicella disease occurring > 42 days after vaccination
Approximately 15-20% of 1-dose vaccinated persons may develop varicella if exposed to VZV
Usually milder clinical presentation than varicella in unvaccinated cases
Usually low or no fever
Develop < 50 lesions
Experience shorter duration of illness
Rash predominantly maculopapular rather
than vesicular
25-30% of breakthrough varicella cases are not
mild and have clinical features more similar to
varicella in unvaccinated persons Chaves J Infect Dis 2008; Arvin Clin Microb Rev 1996; CDC. Prevention of Varicella. MMWR 2007; 56(No. RR-4)
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5. Varicella: Complications
Secondary bacterial infection of skin lesions
Central nervous system manifestations (meningoencephalitis, cerebelllar ataxia)
Pneumonia (viral or bacterial)
Hepatitis, hemorrhagic complications, thrombocytopenia, nephritis occur less frequently
Certain groups at increased risk for complications
Adults
Immunocompromised persons
Pregnant Women
Newborns
CDC. Prevention of Varicella. MMWR 2007; 56(No. RR-4); Arvin Clin Microb Rev 19
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6. Hemorrhagic Varicella

7. Varicella: Transmission
Transmitted person to person by direct contact, inhalation of aerosols from vesicular fluid of skin lesions of acute varicella or zoster, or aerosolized respiratory tract secretions
Period of contagiousness: 1-2 days before rash onset until all lesions crusted or disappear if maculopapular rash (typically 4-7 days)
Varicella in unvaccinated persons is highly contagious (61-100% secondary household attack rate)
Varicella in 1 dose-vaccinated persons half as contagious as unvaccinated cases
CDC. Prevention of Varicella. MMWR 2007; 56(No. RR-4); Arvin Clin Microb Rev 1996; Seward JAMA 2004; Vaccines, 5th edition
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8. Herpes Zoster (Shingles)
Following initial infection (varicella), VZV establishes permanent latent infection in dorsal root and cranial nerve ganglia
Years to decades later VZV reactivates and spreads to skin through peripheral nerves causing pain and a unilateral vesicular rash in a dermatomal distribution
~1 million cases in the U.S. annually
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9. Clinical Features of Herpes Zoster
Prodrome: headache, photophobia, malaise, fever, abnormal skin sensations and pain
Rash:
Unilateral, involving 1-3 adjacent dermatomes
Thoracic , cervical, ophthalmic involvement most common
Initially erythematous, maculopapular
Vesicles form over several days, then crust over
Full resolution in 2-4 weeks
Occasionally, rash never develops (zoster sine herpete)
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10. Complications of Herpes Zoster
Postherpetic Neuralgia (PHN)
Pain ≥ 30 days occurs in 18-30% of zoster cases
Mild to excruciating pain after resolution of rash
Constant, intermittent, or triggered by trivial stimuli
May persist weeks, months or occasionally years
Can disrupt sleep, mood, work, and activities of daily living and lead to social withdrawal and depression
Risk factors for PHN include age ≥ 50, severe pain before or after onset of rash, extensive rash, and trigeminal or ophthalmic distribution of rash
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11. VZV Transmission from Zoster
VZV can be transmitted from persons with zoster
Risk of VZV transmission from zoster is much lower than from varicella
Transmission is mainly through direct contact with zoster lesions, although airborne transmission has been reported in healthcare settings
Localized zoster is only contagious after the rash erupts and until the lesions crust
Transmission from localized zoster can be decreased by covering the lesions

12. Epidemiology

13. Varicella Disease Burden in the United States Before Introduction of Varicella Vaccine in 1995
4 million cases/year
11, ,500 hospitalizations/year
deaths/year
Greatest disease burden in children
>90% cases
70% hospitalizations
50% deaths
Wharton Infect Dis Clin North Am 1996; Galil Pediatr Infect Dis J 2002; Davis Pediatrics 2004; Meyer J Infect Dis 2000; Nguyen NEMJ 2005
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14. Varicella Immunization
Varivax licensed in 1995
In 1995 American Academy of Pediatrics recommended one dose of varicella vaccine for all children < 13, and for susceptible adolescents from 13-18
In 1996 ACIP recommended vaccination for all children < 13 years of age; for susceptible adolescents and adults vaccination recommended for those at high risk of infection or complications. Vaccination of this group deemed desirable.
Pediatrics 1995;95;791. Committee on Infectious Diseases; ACIP. Prevention of Varicella

15. Varicella Immunization
One dose program estimated to save $5 for every $1 spent on vaccine when factoring in parental time lost from work and direct medical costs
When medical costs were considered alone each chicken pox case prevented would cost $2
New Zealand – Total cost savings of $47 per child primarily driven by work-loss time averted
Germany, Taiwan, Singapore

16. Varicella Immunization
Cost-Benefit typically analyze one dose programs
Use of MMRV often not considered
Costs related to hypothetical increase in zoster cases or increase in adult chicken pox cases not considered
High risk groups a better target?
Number of concerns raised include: waning immunity, potentially large pool of susceptible adults, serious complications rare
Newman. Arch Pediatr Adolesc Med 1998; Lieu. JAMA 1994; Ross. BMJ

17. Varicella Active Surveillance Project (VASP)
VASP is a CDC-funded project initiated in 1995 in Philadelphia and Los Angeles County
Purpose of the active surveillance program
To obtain population-based incidence rates for varicella and herpes zoster diseases in a community with established high varicella vaccination coverage rates
to evaluate the impact of current and future varicella vaccination practices and policies

18. 90% decline in varicella incidence in both sites
Varicella Cases and 1-Dose Vaccine Coverage Varicella Active Surveillance Project Sites,
Antelope Valley, California
West Philadelphia
Varicella Cases
Vaccine Coverage
Vaccination coverage
Varicella cases
90% decline in varicella incidence in both sites
Guris J Infect Dis 2008

19. Number of Varicella Outbreaks Antelope Valley, CA 1995-2005

20. Number of Varicella Cases Antelope Valley, CA 1995-2005

21. Length of Outbreaks (Days) and Age of Cases (Years)
Median Length
44.5 Days
30 Days
Median Age
6 Years
9 Years

22. Outbreak Cases: History of Disease or Vaccination and Disease Severity
History of prior varicella disease
6.3%
14%
Breakthrough cases
1.6%
58%
<50 Lesions
35%
45.7%
Complicated disease
9.3%
3.6%

23. Varicella and Measles Vaccine Coverage (1+ doses)
Varicella and Measles Vaccine Coverage (1+ doses)*, Children Months National Immunization Survey,
*National Immunization Survey (NIS), coverage available at
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24. Varicella-Related Hospitalization Rates U.S., 1994-2002
Chart description of Varicella-Related Hospitalization Rates U.S. for Rate per 100,000 Population. Prev-accination years of 1994, and Decline to Overall =88%.
<10 yrs = 91% yrs=92% yrs= 78%.
Decline to 2002
Overall %
< 10 yrs 91%
10-19 yrs 92%
20-49 yrs 78%
Zhou et al, JAMA, 2005

25. Decline in Reported Varicella Deaths <50 years of age, US, 1990-2006
average=85
93% decline in deaths in compared to pre-vaccine era
No. of Deaths
average=8
YEAR
National Center for Health Statistics

26. Experience with 1-dose Varicella Vaccination Program
1-dose varicella vaccination coverage in month-olds increased from 26% to 91% from 1997 to 2008
Varicella disease incidence declined by 90% in two varicella active surveillance sites by 2005 as compared to 1995
Varicella hospitalizations declined 88% during
Varicella mortality rate declined 93% from to in persons aged <50 years
National Immunization Survey ( ); Guris J Infect Dis 2008; Marin Pediatrics 2008; Zhou JAMA 2005; National Center for Health Statistics
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27. Post-licensure One-Dose Vaccine Effectiveness in US*
17 studies with 20 estimates
Study designs: case-control, cohort (outbreaks, other), household contact
Prevention all varicella
Median 85% (range 44% - 100%) Mean 81%
Prevention of combined moderate and severe varicella
Median 97% (range 86% - 100%) Mean 96%
Prevention of severe varicella*
Median 100% (range 97% to 100%) Mean 99%
VARIVAX® Merck and Co. Inc; Seward J Infect Dis 2008
Note: place CDC logo on all slides except #1 – Title slide 27

28. Impressive Achievements with the 1-Dose Varicella Vaccination Program But Challenges to Varicella Control Remained…
15-20% of children vaccinated with 1 dose remain at risk for varicella due to lack of immune response or partial protection
Rationale for Timing of 2nd Dose of Varicella Vaccination at 4-6 Years of Age
Low incidence among 1-4 year old children
Outbreaks in elementary and middle schools
Similar immune response to 2nd dose with intervals 3 months or 3-4 years after 1st dose
Programmatic harmonization with MMR vaccine and availability of MMRV vaccine

29. Current Varicella Vaccination Policy in the United States
Implemented routine 2-dose childhood varicella vaccination program in 2006
1st dose at age months
2nd dose at age 4-6 years
Effectiveness is 98% for prevention of any primary varicella and 100% at prevention of severe disease
CDC. Prevention of Varicella. MMWR 2007; 56(No. RR-4) 29

30. Risk Factors for Herpes Zoster
Increasing age
Immunosuppression
Bone marrow and solid organ transplantation
Patients with hematological malignancies and solid tumors
HIV
Immunosuppressive medications
Gender: Increased risk in females
Race: Risk in African-American less than half that in Caucasians
Trauma or surgery in affected dermatome
Early varicella (in utero, infancy): Increased risk of pediatric zoster
Note: place CDC logo on all slides except #1 – Title slide 30

31. Age-specific Incidence of Herpes Zoster and Postherpetic Neuralgia: U
Age-specific Incidence of Herpes Zoster and Postherpetic Neuralgia: U.K.,
Hope-Simpson J R Coll Gen Pract 1975.

32. Varicella in California

33. Immunization Branch at CDPH
Surveillance and disease reporting to CDC
Technical assistance to local health jurisdictions
Educational materials
Laboratory testing (VRDL)

34. Varicella Reporting in California
Outbreaks
Hospitalizations
Deaths
HZ is not reportable 34

35. Varicella Outbreak Management
>=5 cases associated in time and place
Exclusion of cases while infectious
Provide immunization to susceptible contacts
Provide VarzIG to high risk exposed susceptible contacts (pregnant women)
Exclude susceptible exposed children in a school setting?

36. Reported School Outbreaks in California
Passively reported
2009: 31 outbreaks; Range 5 – 25 cases, median 7 cases
2010: 17 outbreaks; range 5 – 55 cases, median 7 cases
2011: 8 outbreaks; range 5 – 25 cases, median 7 cases
Many requests for technical assistance on outbreak management are related to exclusion of exposed unvaccinated children from school

37. School Varicella Outbreak – October 2011
Child in large unvaccinated family became infected with varicella (source unknown)
All children in family and pregnant mother became infected with varicella over a five week period; mother quite ill
Several siblings attend the same school and were the source of a school outbreak

38. School Varicella Outbreak
School is K-8 with 208 students
66 (38%) students have PBEs
25 cases of varicella
17 (68%) of the cases have PBEs
2 cases had one dose of vaccine and one case had two doses
1 pregnant teacher exposed

39. California Law Granting Exclusion
The California Health and Safety Code section states “…whenever there is good cause to believe that the person [with a personal belief exemption] has been exposed to one of the communicable diseases listed in subdivision (a) of Section , that person may be temporarily excluded from the school or institution until the local health officer is satisfied that the person is no longer at risk of developing the disease.”

40. Pros of School Exclusion
Theoretically may slow a varicella outbreak
May reduce the number of infections and complications
May decrease likelihood of varicella to spread to high-risk people
May encourage parents to vaccinate children who would not otherwise be vaccinated
“Proactive”

41. Cons of School Exclusion
No data that exclusion is effective in slowing a varicella outbreak
Immediate readmittance after vaccination may appear coercive
Childcare costs for parents of excluded children could be substantial
Long exclusion; children may suffer educationally
School law affects cohorts of children differently
Schools need to provide home education or risk losing attendance-based educational funds

42. Outbreak of rash illness in a skilled nursing facility
3 Residents
4 employees
1 visitor (husband of a resident)
Onset dates from 6/3/2012 – 6/21/2012
Ages ranged from 27 – 96 years
VZV source was suspected to be resident with herpes zoster

43. Varicella Immune Status
Onset
Age
Clinical
Affiliation
Result
Varicella Immune Status
6/18 40
lesions in various stages of development covering entire body and inside mouth
Employee
VZV detected
IgG+ in 2008
6/19 65
Lesions; On chronic prednisone therapy
Husband of resident
Presumed immune based on age
Minimal lesions, all dry
History of disease 87
Typical lesions including vesicles
Resident

44. Similar report in the literature
Varicella transmission from HZ patient to 3 persons presumed immune in a long term care facility
Secondary cases were clinically compatible with chicken pox – though mild, <100 lesions and confirmed by PCR
Newly characterized varicella virus

45. Varicella Reinfection?
Reinfection has been previously described but is rare
Hall (2002) reviewed 9,947 varicella cases and found that between 4.5% and 13.3% of cases reported a history of varicella infection
Case report on physician with prior evidence of serologic immunity

46. Varicella Death, 2010 41 yo male previously healthy
Presented with 5 days history of abdominal pain and fever of 100.5
Presented to the ER the following day after developing a generalized rash; discharged with acyclovir
Developed mild delirium and difficulty breathing
Complications included encephalitis and hepatitis
Patient expired 9 days after admission

47. Varicella Death, 2007
13 month old previously healthy unvaccinated female
Presented to ED with fever to 102 and vesicular rash; diagnosed with chicken pox
Five days after rash onset patient became weak and unable to ambulate
Admitted and administered IV acyclovir
Patient expired 6 days after rash onset

48. Questions? Acknowledgements Centers for Disease Control and Prevention
Kathy Harriman
Teresa Lee
CDPH Immunization Branch

49. California School Immunization Law
Immunization requirements at kindergarten entry:
4+ DTaP, 3+ polio, 2 MMR, 3 hepatitis B, 1 varicella
Exemptions and procedure
Permanent and Temporary Medical
Personal Beliefs (PBE)
“shall be granted upon filing with the [school] a letter or affidavit from the pupil’s parent…that such immunization is contrary to his or her beliefs”

50. Two-fold Purpose Method PBE Study – California, 2009
To evaluate vaccination status of kindergarten PBEs
Determine whether ‘high’ PBE schools were different from ‘standard’ PBE schools
Method
Collected and analyzed PBE records from:
a random sample of kindergartens and
the top 50 PBE kindergartens
Two-fold Purpose
To evaluate vaccination status of kindergarten PBEs
Determine whether ‘high’ PBE schools were different from ‘standard’ PBE schools
Method
Collected and analyzed immunization records of personal beliefs exemptors from:
a Random sample of kindergartens and
the Top 50 PBE kindergartens 50

51. Percent of Nonblank PBE Records Missing All Doses in Series
% of PBEs
You can see that students taking an exemption for the 4+ dose DTP series locatedon the far left comprised only 4 percent of the nonblank exemptor records for both samples.. You can see that, for the 3 dose Polio requirement, twice as many students chose an exemption as compared to those taking an exemption for the 4+ doses of DTP. Likewise twice as many students took an exemption for the 2 doses of MMR as compared with those taking the exemption for the 3 doses of polio. For those taking the exemption for the 3 doses of Hepatitis B, Taking a look at the last vaccine requirement, one dose of varicella, you can see here that varicella was exempted the most.
four percent (or 5/124) were missing all doses of DTP
7.3 percent (or 9/124) were missing all doses of Polio
13.7 (or 22/124) percent were missing the two required doses of MMR
17.7 (or 17/124) percent were missing the three required dose of Hep B
And 33.9 (or 42/124) percent were missing the one required varicella dose
202 records were missing at least one DTP vaccine; 116 records were missing all doses of DTP (4)
194 records were missing at least one polio vaccine ; 120 records were missing all doses of Polio (3)
205 records were missing at least 1 MMR vaccine; 133 records were missing all doses of MMR (2)
151 records were missing at least 1 HepB; 128 records were missing all doses of HepB (3)
153 records were missing the one required Varicella dose; 153 records were missing all doses of Var (1) 51

52. 1977: Requirements for DTP, polio, measles passed, effective Jan 1, 1978;
Started annual assessments
1979: Requirements for mumps and rubella added, effective Jan 1, 1980
1995: Requirement for hepatitis B added, effective Aug 1, 1997
1999: Requirement for varicella added, effective Jul 1, 2001 52