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) Note: place CDC logo on all slides except #1 – Title slide 2

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) Note: place CDC logo on all slides except #1 – Title slide 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 Note: place CDC logo on all slides except #1 – Title slide 5

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 Note: place CDC logo on all slides except #1 – Title slide 7

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 Note: place CDC logo on all slides except #1 – Title slide 8

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) Note: place CDC logo on all slides except #1 – Title slide 9

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 Note: place CDC logo on all slides except #1 – Title slide 10

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 Note: place CDC logo on all slides except #1 – Title slide 13

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

90% decline in varicella incidence in both sites Varicella Cases and 1-Dose Vaccine Coverage Varicella Active Surveillance Project Sites, 1995-2005 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

Number of Varicella Outbreaks Antelope Valley, CA 1995-2005

Number of Varicella Cases Antelope Valley, CA 1995-2005

Length of Outbreaks (Days) and Age of Cases (Years) 1995-1998 2002-2005 Median Length 44.5 Days 30 Days Median Age 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) Varicella and Measles Vaccine Coverage (1+ doses)*, Children 19-35 Months National Immunization Survey, 1997-2008 *National Immunization Survey (NIS), coverage available at http://www.cdc.gov/vaccines/stats-surv/default.htm#nis Note: place CDC logo on all slides except #1 – Title slide 23

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 average=85 93% decline in deaths in 2005-2006 compared to pre-vaccine era 1990-1994 No. of Deaths 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 Note: place CDC logo on all slides except #1 – Title slide 26

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

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) 29

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

Age-specific Incidence of Herpes Zoster and Postherpetic Neuralgia: U 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 34

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

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

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”

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

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

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