National Center for Immunization & Respiratory Diseases

25 Years of Varicella Vaccination Program in the Un

Health and Economic Impact during 1995–2

Mona Marin, MD

Centers for Disease Control and Prevention, Atlanta, 

Advisory Committee on Immunization Practices 

Atlanta, GA 

February 23, 2023

Division of Viral Diseases
Varicella: from rite of passage to vaccine-prevent

 Historically, varicella was considered disease of little consequen

warrant prevention

 Mid-1950s: first reported fatal varicella cases in children treate

introduced immunosuppressive therapy unmasked the lethal pvaricella-zoster virus (VZV)

1

1Cheatham et al. Am J Pathol 1956; 32:1015-35. 

Child with leukemia who died of varicella, ~1970 (courtesy of Dr. A
Iatrogenic immunosuppression: 

systemic steroid therapy, organ transplant, childhood cancer• Leukemia cured in 80% of children 

but many died of varicella before immune reconstitution

US trials in children with leukemia demonstrated vaccine efficacy and safety2

• Subsequent studies showed 

safety and efficacy in healthy children and adults

Varicthe U• F

vp

1960s/70s

1974

1980s

Gershon at al. JID 2021. Marin et al. JID 2022. In press. 1Takahashi et al. Lancet 1974 2Gershon e

Varicella: from rite of passage to vaccine-prevent

Varicella vaccine (Japan), VZV attenuated, healthy children and adults and children with leukemia in remission1• Initial controversy in the U.S.: 

risk for latency and persistence of immunity 
Debate around the 

time of varicella vaccine recommendations

Does the health 

burden of 

varicella justify a 

vaccination 

program?

Woul

vaccin

accept

parent

provid

Would the 

varicella 

program shift 

burden from 

children to 

adults?

Woul

varicella 

increa

incide
U.S. Varicella Vaccination Program
Before vaccine, varicella represented a significa

burden (medical and societal) in the United Sta

Annual average, pre-vaccine Cases ~4 million Hospitalizations ~10,500–13,500 Deaths ~100–150 Congenital varicella syndrome ~44 Greatest disease burden in children

– >90% cases, 70% hospitalizations, 50% deaths

Wharton et al. 1996, Galil et al. 2001, Davis et al

. 2004, Meyer et al. 2000, Nguyen et al. 2005, Enders 
Varicella vaccine policy in the United States

 1995: Routine one-dose 

– One dose routinely at age 12–18 months with 

catch-up vaccination of older children

– Two doses for susceptible persons aged ≥13 years

 2007: Policy changed to routine 2-dose 

–

1st dose at age 12–15 months

–

2nd dose at age 4–6 years

– Catch-up vaccination of persons who had received 

one dose

– Vaccination of all eligible persons without 

evidence of immunity

MMWR 2007;56(RR-4):1–39 . Available at www.cdc.gov

Rationale  Low-le

transm

 Outbr

dose vpopulless fr
Vaccination coverage for ≥1 dose varicella 

and ≥1 dose MMR, children age 19–35 months, US 1996–2020Data Source: National Immunization Survey

≥ 1 dose 

varicella

≥ 1 dose 

MMR

0

102030405060708090

100

1996 2000 2004 2008 2012 2016 2020

Percent Vaccinated

Year

Elam-Evans et al. JID 2022.

Average 2-dose 

varicella

Average 2-dose 

MMR

0%

10%20%30%40%50%60%70%80%90%

100%

2006 2008 2010 2012 2014 

Percent Vaccinated

Year

Vaccination coverage for and ≥2 doses MMR, childyears — 6 US states, 2006Data Source: Immunization Inform

Program implementation was highly successful
Post-licensure vaccine effectiveness among ch

HIV+ children (2 doses, 1 study)- 82% (95% CI 24%–100%)

1

Marin et al. Pediatrics 2016. 

1Son et al. JID 2010. 

*Definitions: 1) Varicella with >500 lesions or a complication requiring physician visit; 2) disease severitrials: # lesions, fever, systemic signs and subjective assessment of illness

Varicella Endpoint 1 dose VE 2 dose Varicella of any severity

82%

(Meta-analysis)

92%

(Meta-ana

Moderate and Severe disease

97%

(Median)

Severe* disease 100%

(range= 97-100)
Impact of 25 Years of the U.S. Varicella Vac

Program on Varicella
Varicella incidence* declined >97%, 1990–20

*4 states with consistent reporting of cases to the National Notifiable Diseases Surveillance System. Marin et al. JID, 2022. 
Varicella incidence declined in all age groups d

2-dose program*.

0

50

100150200250

<1 1–4 5–9 10–14 15–19 20-29

Incidence per 100,000 

population

Age group (years)

2005-20062018-2019

-76% -74% -95% -92% -64% -15% 

*29 states and the District of Columbia reported age data during 2005–2006 (end of 1-dose program) a(mature 2-dose program); National Notifiable Diseases Surveillance System data; Marin et al. JID 2022§Outbreak: ≥5 varicella cases; Leung et al. JID 2022. 

In 7 states with consistent reporting, the number of outbreaks 
Varicella hospitalizations declined 90% during 

Marin et al. JID 2022. Data: HCUP National Inpatient Sample (NIS). 
>10,500 hospitalizations are prevented now an

including >1,250 among infants.

Marin et al. JID 2022. Data: HCUP National Inpatient Sample (NIS). 

Age Group Average annual no. 

hospitalizations

1993-95

Average annual no. 

hospitalizations

2018-19

hosp

<1 1,338 55 

1-4 4,309 80 

<20 8,574 285 <50 11,573 783 

All ages 12,189 1,390 
Varicella as the underlying cause of death. National Center for Health Statistics data. 

Marin et al. JID 2022. 

Varicella mortality declined 89% during 1990

Most of the decline occurred during the 1-dose program
Deaths practically eliminated among <20-year-

No varicella deaths (underlying or contributing) reported in the <20 years age group in 2011, 2013, 2014Center for Health StatisticsMarin et al. JID 2022. 

0

20406080

100120

20-49 yrs (94% redu<20 yrs (99.4% redu

Year

Deaths with varicella as the underlying cause,

persons aged <50 years-old, 1990-2019

Number of deaths
Herpes Zoster Trends During the U.S. Varic

Vaccination Program 
In persons aged ≥30 years, HZ incidence increa

the earlier study years, with decelerations in la

Leung et al. JID 2022. MarketScan 1998–2019. 

30-39

40-49

50-59

60-69

≥70

Total

0.02.04.06.08.0

10.012.0

HZ Incidence per 1000 Persons

Year
In children and young adults, HZ incidence decl

step-wise pattern once each age group was compersons born during the varicella vaccination p

Leung et al. JID 2022. MarketScan 1998–2019. 

1-4

5-9

10-14 15-19

20-24

0123

HZ Incidence per 1000 Persons

Year

HZ ifor rHZ ifor r
US varicella vaccination resulted in substantial dise

and societal savings over 25 years of program imple

High vaccine 

coverage reached

Effective, safe, and 

accepted vaccine

91 million cases 

1,933-2,446 deaths

238,000 hospitalizations

Prevented morbidity & 

mortality

$23.4 

billion

in net 

societal savings

Highly cost saving

Re

c

N

t
The Journal of Infectious Diseases supplement 

November 1st, 2022

https://academic.oup.com/jid/iss

The varicella vaccination program in the US: 25 years of saving lives and preventing illness 
Acknowledgements 

Co-authors Jessica Leung Kathleen Dooling Tara Anderson Adriana Lopez Michael Melgar Aaron Curns Fangjun ZhouNurses, physicians, pharmacistsState and local health department staff Varicella active surveillance project staffCDC Division of Viral Diseases past/present staff 

JID supplement co

 Jane Seward Anne Gershon Laurie D. Elam-E Eugene Shapiro Sheila Dollard Ann Arvin Marci Drees Ismael Ortega-S Rafael Harpaz Alexandra Hess Lauren Pearson Olga Munteanu Janine Cory Nina Masters
For more information, contact CDC

1-800-CDC-INFO (232-4636)TTY: 1-888-232-6348 www.cdc.govThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Thank You