Varicella (Chickenpox) and Herpes
Zoster (Shingles)
Jennifer Zipprich
Immunization Branch
California Department of Public Health
October 17th, 2012
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)
Varicella Clinical Features
• Incubation period 14-16 days
(range 10-21 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
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)
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
Hemorrhagic Varicella
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
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
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)
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
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
Epidemiology
Varicella Disease Burden in the United States
Before Introduction of Varicella Vaccine in 1995
•
•
•
•
4 million cases/year
11,0000 - 13,500 hospitalizations/year
100 - 150 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
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. 1996.
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
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. 1995.
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
Varicella Cases and 1-Dose Vaccine Coverage
Varicella Active Surveillance Project Sites, 1995-2005
Varicella Cases
3500
100
3000
80
2500
1400
100
1200
80
1000
2000
60
1500
40
60
800
40
1000
600
20
400
20
500
0
200
0
0
1995
1997
1999
2001
2003
2005
Year
Vaccination coverage
0
-20
1995
1997
1999
2001
2003
2005
Year
Varicella cases
90% decline in varicella incidence in both sites
Guris J Infect Dis 2008
Vaccine Coverage
West Philadelphia
Antelope Valley, California
Number of Varicella Outbreaks
Antelope Valley, CA 1995-2005
No. of Outbreaks
100
80
81
60
68
67
54
40
34
20
30
14
0
1995
1996
1997
1998
1999
2000
Year
2001
25
8
6
2002
2003
8
2004
2005
Number of Varicella Cases
Antelope Valley, CA 1995-2005
Non-outbreak Cases
Outbreak Cases
3500
No. of Cases
3000
2500
2000
1500
1000
500
0
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Year
Length of Outbreaks (Days) and
Age of Cases (Years)
Median Length
Median Age
1995-1998
2002-2005
44.5 Days
30 Days
6 Years
9 Years
Outbreak Cases: History of Disease or
Vaccination and Disease Severity
1995-1998
2002-2005
History of prior varicella
disease
6.3%
14%
Breakthrough cases
1.6%
58%
<50 Lesions
35%
45.7%
Complicated disease
9.3%
3.6%
Varicella and Measles Vaccine Coverage
(1+ doses)*, Children 19-35 Months
National Immunization Survey, 1997-2008
100
90
81
Coverage (%)
80
85
88
88
89
90
91
76
68
70
58
60
50
43
Varicella
Measles
40
30 26
20
10
0
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Year
*National Immunization Survey (NIS), coverage available at
http://www.cdc.gov/vaccines/stats-surv/default.htm#nis
Varicella-Related Hospitalization Rates
U.S., 1994-2002
Chart description of Varicella-Related Hospitalization Rates U.S. for
1994-2002. Rate per 100,000 Population. Prev-accination years
of 1994, and 1995.
Decline 1994-95 to 2002. Overall =88%.
<10 yrs = 91%. 10-19 yrs=92%.20-49 yrs= 78%.
Decline 1994-95 to
2002
Overall
88%
< 10 yrs 91%
10-19 yrs 92%
20-49 yrs 78%
Zhou et al, JAMA, 2005
Decline in Reported Varicella Deaths
<50 years of age, US, 1990-2006
No. of Deaths
average=85
93% decline in deaths in 2005-2006
compared to pre-vaccine era 1990-1994
average=8
YEAR
National Center for Health Statistics
Experience with 1-dose Varicella Vaccination
Program
• 1-dose varicella vaccination coverage in 19-35 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 1994-2002
• Varicella mortality rate declined 93% from 1990-1994 to
2005-2006 in persons aged <50 years
National Immunization Survey (www.cdc.gov/vaccines/stat-surv/default.htm#nis ); Guris J Infect Dis 2008;
Marin Pediatrics 2008; Zhou JAMA 2005; National Center for Health Statistics
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
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
Current Varicella Vaccination Policy
in the United States
Implemented routine 2-dose
childhood varicella vaccination
program in 2006
 1st dose at age 12-15 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)
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
Age-specific Incidence of Herpes Zoster and
Postherpetic Neuralgia: U.K., 1947-1972
Hope-Simpson J R Coll Gen Pract 1975.
Varicella in California
Immunization Branch at CDPH
•
•
•
•
Surveillance and disease reporting to CDC
Technical assistance to local health jurisdictions
Educational materials
Laboratory testing (VRDL)
Varicella Reporting in California
•
•
•
•
Outbreaks
Hospitalizations
Deaths
HZ is not reportable
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?
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
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
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
California Law Granting Exclusion
• The California Health and Safety Code section
120365 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 120325, 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.”
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”
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
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
Age
Clinical
Affiliation
Result
Varicella
Immune Status
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
VZV detected
Presumed
immune based
on age
6/19
40
Minimal lesions, all dry
Employee
VZV detected
History of
disease
87
Typical lesions including
vesicles
Onset
6/18
6/19
Resident
VZV detected
Presumed
immune based
on age
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
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
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
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
Questions?
Acknowledgements
• Centers for Disease Control and Prevention
• Kathy Harriman
• Teresa Lee
• CDPH Immunization Branch
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”
PBE Study – California, 2009
• 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 PBE records from:
a random sample of kindergartens and
the top 50 PBE kindergartens
Percent of Nonblank PBE Records
Missing All Doses in Series
50
% of PBEs
40
28.9
30
20
10
41.8
Random
Top 50
16.1
4 3.7
30.2
33.3
17.5
13.5
7.1
0
DTaP
Polio
Hep B
MMR
Var
Increase in Permanent Medical (PME) and Personal Beliefs (PBE)
Exemptions Among Kindergarten Students, California 1977-2009
Percent of Students
2.5%
2.0%
Measles,
mumps and
rubella
requirement
Measles
outbreak
Varicella
requirement
Hepatitis B
requirement
1.5%
1.0%
0.5%
0.0%
1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009
PME
PBE
Year of Assessment