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National  Center  for Immunization  & Respiratory  Diseases 
Division  of Viral  Diseases 
25 Years of Varicella Vaccination Program in the United States: 
Health and Economic Impact during 1995–2019 
Mona Marin, MD 
Centers for Disease Control and Prevention, Atlanta, GA 
Advisory Committee on Immunization Practices 
Atlanta, GA 
February 23, 2023 
         
          
 
          
         
 
                   Varicella: from rite of passage to vaccine- preventable disease. 
 Historically, varicella was considered disease of little consequence, too mild to 
warrant prevention 
 Mid-1950s: first reported fatal varicella cases in children treated with newly introduced immunosuppressive therapy unmasked the lethal potential of the varicella-zoster virus (VZV)
1 
Child with leukemia who died of varicella, ~1970 (courtesy of Dr. Anne Gershon) 
1Cheatham et al. Am J Pathol 1956; 32:1015-35. 2 
                                                  Varicella: from rite of passage to vaccine- preventable disease. 
Iatrogenic  immunosuppression  : 
systemic  steroid  therapy, organ  
transplant, childhood  cancer US trial  s in children  with  leukemi  a 
demonstrated  vaccine  efficacy  and  
safety2 
• Leukemia  cured  in 80%  of childre  n 
but many  died  of varicell  a before  
immune  reconstitution •  Subsequent  studies  showe  d 
safety  and efficacy  in healthy  
children  and adults 1974 1995 
Varicell  a vaccine  (Japan), VZV  
attenuated, healthy  children  and  
adults  and children  with  
leukemi  a in remission1 
• Initia  l controversy  in the U.S.  : 
risk for latency  an d 
persistence  of immunit  y Varicell  a vaccine  licensed  in  
the U.S . 
• First  country  with  a routine  
varicell  a vaccinatio  n 
program 1960s/70s 1980s 
Gershon at al. JID 2021. Marin et al. JID 2022. In press. 1Takahashi et al. Lancet 1974 2Gershon et al. JAMA 1984. 3 
Debate  around  t he 
time   of varicell  a 
vaccine  
recommendatio nsDoes  the health  
burden  o f 
varicella  justify   a 
vaccination  
program? 
Would  th e 
varicell  a 
program  shif  t 
burden  fro  m 
children  to  
adults? 
Would  th e 
vaccine  b e 
accepted  b y 
parents  and  
providers? 
Would  th e 
varicella  progra  m 
increase  H Z 
incidence? 
4 
U.S. Varicella  Vaccination Program

       
        
  
 
   
    
     
                       
Before vaccine, varicella represented a significant health 
burden (medical and societal) in the United States. 
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 and Miller. 2000 6 
      
   
        
    
       
      
    
    
       
 
      
  
       Varicella vaccine policy in the United States 
 1995: Routine one-dose 
– 
–  
 
– 
– 
– 
– O ne dose routinely at age 12–18 months with 
catch-up vaccination of older children R
ationale for policy change 
Two doses for susceptible persons aged ≥13 years Low-level  community  
transmission  continued 
 2007: Policy changed to routine 2-dose Outbreaks  in highly  1-
dose  vaccinated  school  
populations  (smaller  , 
less frequent) 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 7 
     100% 
90% 
Average 2-dose 
varicella Average 2-dose 
MMR 
2006 2008 2010 2012 2014 2016 2018 2020 80% Percent Vaccinated 70% 
60% 50% 40% 
30% 
20% 
10% 
0% 
Year 
8        100 
90 
≥ 1 dose 
80 MMR ≥ 1 dose Percent Vaccinated varicella 70 
60 
50 40 
30 
10 20 
1996 2000 2004 2008 2012 2016 2020 
Year 0 
        Program implementation was highly successful. 
Vaccination  coverage  for ≥1 dose  varicell  a 
and ≥1 dose MMR,  children  age 19–35  
months,  US 1996–2020 
Data  Source:  National  Immunization  Survey Vaccination  coverage  for ≥2 doses  varicell  a 
and ≥2 doses  MMR,  children  by age 7  
years  — 6 US states,  2006–2020 
Data  Source:  Immunization  Information  System 
Elam-Evans et al. JID 2022. 
    
     
                            
               
   
  
 
 
 Post-licensure vaccine effectiveness among children 
Varicella Endpoint 1 dose VE 2 dose VE 
Varicella of any 
severity 82% 
(Meta-analysis) 92% 
(Meta-analysis) 
Moderate and Severe disease 97% 
(Median) 
Severe* disease 100% 
(range= 97-100) 
HIV+ children (2 doses, 1 study)- 82% (95% CI 24%–100%)1 
*Definitions: 1) Varicella with >500 lesions or a complication requiring physician visit; 2) disease severity scale used in clinical 
trials: # lesions, fever, systemic signs and subjective assessment of illness 
Marin et al. Pediatrics 2016. 1Son et al. JID 2010. 9 
Impact  of 25  Years  of the U.S. Varicella Vaccination  
Program  on Varicella 

   
              
     Varicella incidence* declined >97%, 1990–2019. 
*4 states with consistent reporting of cases to the National Notifiable Diseases Surveillance System. 
Marin et al. JID, 2022. 11 
         
   
  0 50 100 150 200 250 Incidence per 100,000 
population 2005-2006 
2018-2019 
-76% -18% -15% -64% -92% -95% -74% 
<1 1–4 5–9 10–14 15–19 20-29 ≥30 
Age group (years) 
                  
              
                    Varicella incidence declined in all age groups during the 
2-dose program*. 
In 7 states with consistent reporting, the number of outbreaks declined 82%§ 
*29 states and the District of Columbia reported age data during 2005–2006 (end of 1-dose program) and 38 during 2018–2019 
(mature 2-dose program); National Notifiable Diseases Surveillance System data; Marin et al. JID 2022. 
§Outbreak: ≥5 varicella cases; Leung et al. JID 2022. 12 
Varicella hospitalizations declined 90% during 1993–2019. 
     
            Marin et al. JID 2022. Data: HCUP National Inpatient Sample (NIS). 13 
      
   
                     
 
 >10,500 hospitalizations are prevented now annually, 
including >1,250 among infants. 
Age Group Average annual no. 
hospitalizations 
1993-95 Average annual no. 
hospitalizations 
2018-19 Decline in 
hospitalization rate 
<1 1,338 55 -96% 
1-4 4,309 80 -98% 
<20 8,574 285 -97% 
<50 11,573 783 -94% 
All ages 12,189 1,390 -90% 
Marin et al. JID 2022. Data: HCUP National Inpatient Sample (NIS). 14 
            
          
        Varicella mortality declined 89% during 1990–2019. 
Most of the decline occurred during the 1-dose program. 
Varicella as the underlying cause of death. National Center for Health Statistics data. 
Marin et al. JID 2022. 15 
    
                    
   
        
        
      Deaths practically eliminated among <20-year-olds. 
Deaths with varicella as the underlying cause, 
persons aged <50 years-old, 1990-2019 
0 20 40 60 80 100 120 20-49 yrs (94% reduction) 
<20 yrs (99.4% reduction) Number of deaths 
Year 
No varicella deaths (underlying or contributing) reported in the <20 years age group in 2011, 2013, 2014, 2017, 2018. Data: National 
Center for Health Statistics Marin et al. JID 2022. 
16 
Herpes  Zoster  Trends  During  the U.S. Varicell  a 
Vaccination  Program  

         
         
          In persons aged ≥30 years, HZ incidence increased during 
the earlier study years, with decelerations in later years. 
30-39 40-49 50-59 60-69 ≥70 
Total 
0.0 2.0 4.0 6.0 8.0 10.0 12.0 HZ Incidence per 1000 Persons 
Year 
Leung et al. JID 2022. MarketScan 1998–2019. 18 
          
         
      
              
  
    
  In children and young adults, HZ incidence declined in a 
step-wise pattern once each age group was comprised by persons born during the varicella vaccination program. 
HZ incidence before opportunity 
for routine varicella vaccination HZ incidence after opportunity for routine varicella vaccination 
1-4 5-9 10-14 15-19 20-24 
0 1 2 3 HZ Incidence per 1000 Persons 
Year 
Leung et al. JID 2022. MarketScan 1998–2019. 19 
        
        US varicella vaccination resulted in substantial disease prevention 
and societal savings over 25 years of program implementation. 
20 Effective,  safe,  and  
accepted  vaccine 
High  vaccin  e 
coverage  reached Prevented  morbidity &  
mortality 
91 million  cases  
238,000  hospitalizations 
1,933-2,446  deaths Highly  cost saving 
$23.  4 
billion 
in ne t 
societal  savings No increase  in HZ due  
to varicella program 
Reduced  HZ incidence  i n 
children/adolescents 

     
     
    
      
  
The varicella vaccination 
program in the US: 25 years of saving lives and preventing illness 
The Journal of Infectious Diseases supplement 
November 1st, 2022 
https://academic.oup.com/jid/issue/226/Supplement_4 
21 
 
 
 
      
    
         Acknowledgements 
Co-authors 
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 
 
 
  
 
   
 
  
 
  
 
  Jessica  Leung 
Kathleen  Dooling 
Tara  Anderson 
Adriana  Lopez 
Michael  Melgar 
Aaron  Curns 
Fangjun  Zhou 
N
urses, physicians, pharmacists 
State and local health department staff 
Varicella active surveillance project staff 
CDC Division of Viral Diseases past/present staff JID supplement contributors 
Jane  Seward 
Anne  Gershon 
Laurie  D. Elam-Evans 
Eugene  Shapiro 
Sheila  Dollard 
Ann Arvin 
Marci  Drees 
Ismael  Ortega-Sanchez 
Rafael  Harpaz 
Alexandra  Hess 
Lauren  Pearson 
Olga  Munteanu 
Janine  Cory 
Nina  Masters 
    
 
      
                  
          Thank You 
For more information, contact CDC 
1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov 
The 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.