1. Varicella Disease Incidence During the Introduction of a Routine Two Dose Varicella Vaccination Program, Antelope Valley, California,
Amanuel Hussien, MSc, MSW
Research Analyst
Varicella Active Surveillance Project
Los Angeles County Department of Public Health
Good Afternoon-
Today I will report on varicella disease incidence during the introduction of a routine 2 dose varicella vaccination program in Antelope Valley, CA. The period of interest is from , which encompasses 2 years prior to 2 doses varicella vaccination and 2 years after the introduction. However, some of the slides will review surveillance data commencing in 2000.

2. Background: Varicella Vaccination Recommendations
March 1995: Live attenuated varicella vaccine licensed in U.S.
1995: Recommendations by ACIP & AAP
1 dose recommended for children months
Vaccination of susceptible older children, adolescents and adults
June 2006: Updated ACIP Recommendations
Additional 2nd dose of varicella vaccination to vaccine schedule for children 4-6 years
Adults and adolescents > 13 yrs- 2 doses
Let’s review the history of varicella vaccination in the U.S.
March 1995: Live attenuated varicella vaccine licensed in U.S.
1995: Recommendations by ACIP (American College of Immunization Practices) & AAP (American Academy of Pediatrics)
1 dose recommended for children months
Vaccination of susceptible older children, adolescents and adults
Adults and adolescents > 13 yrs- 2 doses, 4-8 weeks apart
Despite the overall decline in varicella incidence, there were increasing reports of varicella outbreaks among highly vaccinated population. As a result, in June 2006: Recommendation of additional 2nd dose of varicella vaccination to childhood vaccination schedule for children 4-6 years

3. Varicella Active Surveillance Project, Antelope Valley, CA
Project funded by Centers for Disease Control and Prevention
One of two national sites for carrying out varicella and herpes zoster (HZ) surveillance
Varicella surveillance: January 1, present
VASP is a joint cooperative research project with the CDC.
One of two national sites for carrying out varicella and herpes zoster (HZ) surveillance- our second site in in West Philadelphia, PA
Varicella surveillance has been conducted since- January 1, present

4. Study Site: Antelope Valley, California
Geographically circumscribed
Located in Northeastern corner of Los Angeles County (LAC)
Assumption: Most people that live in the Antelope Valley (AV) get their medical care locally and children attend schools in AV
~ 2,200 square miles with total population ~ 366,000
Mean birth cohort: 5,800 infants
The Antelope valley in California is located in the northern Los Angeles County and the southeastern portion of Kern County and western tip of the Majove Desert. It is high desert community covers 2,200 square miles with total population 366,000. It is assumed that most people that live in the Antelope Valley get their medical care locally and children attend school in Antelope Valley. From the mean birth cohort was 5,800 infants.
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5. *National Immunization Survey Data
Varicella Vaccination Coverage among Children months*, Los Angeles County, CA ,
Now let’s look at varicella vaccination coverage in Los Angeles County collected annually by the National Immunization Survey.
Since 1996 single dose varicella vaccination coverage for children between months has increased from 13% to over 90%., Coverage has maintained at over 90% since 2002.
*National Immunization Survey Data
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6. Objectives (1)
Describe age- specific varicella incidence rate (IR) trends from
Describe varicella vaccine doses administered in surveillance area from
Compare IR of varicella disease during end of single dose varicella vaccination era ( ) compared to IR from initiation of two dose era ( )
Calculate relative risk (RR) of 1 dose exposure IR versus 2 dose exposure IR for varicella disease
The objectives of this presentation are :
Describe age- specific varicella incidence rate (IR) trends from
Describe varicella vaccine doses administered in surveillance area from
Compare IR of varicella disease during end of single dose varicella vaccination era ( ) compared to IR from initiation of two dose era ( ).
Compare the proportion of verified breakthrough (BT) varicella during the 2 time periods.
Describe the clinical presentation of varicella disease during these 2 time periods.

7. Objectives (2)
Compare the proportion of verified breakthrough (BT) varicella during the 2 time periods
Describe the clinical presentation of varicella disease during these 2 time periods
The objectives of this presentation are :
Describe age- specific varicella incidence rate (IR) trends from
Describe varicella vaccine doses administered in surveillance area from
Compare IR of varicella disease during end of single dose varicella vaccination era ( ) compared to IR from initiation of two dose era ( ).
Compare the proportion of verified breakthrough (BT) varicella during the 2 time periods.
Describe the clinical presentation of varicella disease during these 2 time periods.
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8. Methods: Data Collection
Cases ascertained through active surveillance
Surveillance sites report every 2 weeks, even if no cases identified
Reporting sites (n=310) include schools, day cares, healthcare providers, large employers
Each case interviewed by telephone to collect detailed demographic and clinical data
Surveillance sites report vaccine doses by age quarterly
Merck also reports to the project annual vaccine doses supplied to Antelope Valley
The VASP conducts varicella case surveillance through active surveillance-
All surveillance sites report every 2 weeks, even if no cases identified
Reporting sites (>300) include schools, day cares, healthcare providers, large employers, etc.
Each case interviewed by telephone to collect detailed demographic and clinical data
Clinical data- rash description, # lesions, accompanying symptoms (i.e. fever, sore throat), complications, antiviral treatment
Vaccine providers reported varicella vaccine doses administered by age group on a monthly basis. In addition, Mark also reports to the project annual vaccine doses supplied to Antelope Valley.

9. Case Definitions Verified varicella case
Acute onset diffuse papulovesicular rash without other known cause (diagnosed by parent, school, medical provider)
Case report completed validating the clinical diagnosis
Resident of Antelope Valley
Breakthrough varicella case
Illness >42 days after varicella vaccination
Let’s review our case definitions:
Verified varicella case
Acute onset diffuse papulovesicular rash without other known cause (diagnosed by parent, school, medical provider)
Completion of case report validating the clinical diagnosis
Resident of Antelope Valley
Breakthrough varicella disease
Meets criteria of verified varicella case
Varicella disease > 42 days after vaccination (confirmed by immunization record or provider office)

10. Methods: Data Analysis
Incidence Rate (IR) calculation
Numerator- all verified varicella cases for the specified year
Denominator- age-specific US census data for Antelope Valley by specified year
Compare 2 year IR: versus
Mantel Haenzel RR: to compare incidence rates and
Chi square test
All data was entered via Microsoft Access and data analysis was performed with SAS 9.2. Only verified cases were included in the analysis. Varicella incidence rate were calculated using US AV census data as denominators. The relative risk of acquiring varicella in the one dose era compared to the 2-dose vaccine era was calculated comparing the incidence of varicella from to the incidence of varicella during The Chi-square test was used to assess statistical significance among variables.

11. Results: Total Annual Varicella Vaccine Doses Administered, Antelope Valley, CA, 2000 - 2008
Now let’s look at the total vaccination doses administered by vaccine providers since 2000
Total vaccination doses in AV VASP increased from 5,721 doses to over 18,000 doses. Increases notable by 2007 with 2nd dose requirement.
From 2006 to the vaccine doses increased from 14,858 in to 37,107 doses in

12. Results: Annual Varicella Vaccine Doses by Age-Group, Antelope Valley, CA, 2000 - 2008
This slide presents the annual vaccine doses ADMINSTERED by specific age group IN ANTELOPE VALLEY DURING
The violet represents the 1-2 year age group, the group where the 1st dose of varicella vaccine has been consistently recommended, this is the group where the greatest proportion of vaccine has been administered. YOU CAN see the vaccine doses increased IN THIS AGE GROUP from 2000 through For unclear reason, the total number of vaccine doses in this age group declined slightly in
After the 1-2 year old group, the 5-9 year old group had the 2nd to the largest amount of delivered doses. This is most likely due to the school entry requirement, starting in 1999 in CA.
With the 2nd dose recommendation, vaccination doses ADMINISTERED increased significantly in the 5-9 year, 10-12, and AGE GROUPS in THERE WERE 37,107 doses ADMINISTERED in 2007 and 2008 compared to 14,983 in 2005 and 2006.

13. Results: Overall Varicella Incidence Rates by Year, Antelope Valley, CA, 2000-2008
With corresponding increasing in vaccine doses delivered to the surveillance sites, there was an overall varicella IR declined from Overall varicella IR from 2000 has declined from 2.7 per 1000 population to -0.6 per The numbers of cases were also declined by 286% from 2000 to This decline steadily continued from

14. Results: Age-Specific Varicella Incidence Rates, Antelope Valley, CA, 2000-2008
Age specific incidence rates across all age groups from showed a steady decline. There is a noticeable increase in DUE TO a resurgence of breakthrough varicella outbreaks. We see in all age groups, especially 5-9 years. Varicella IR declined with consistent stead decline across all groups with the exception of year old group.

15. Results: Age-specific Varicella Incidence Rate, Antelope Valley, CA, 2005-2008
Age-group RR
(95% CI)
P-Value
n (%) IR
< 1*
36 (4.8)
3.3
24 (4.7)
2.0
1.7 ( )
0.0422*
1 – 4*
92 (12.1)
2.2
72 (14.0)
1.5
1.5 ( )
0.0246*
5 – 9**
286 (37.8)
5.4
179 (34.9)
3.5
1.5 ( )
0.0001**
10 – 14**
249 (32.9)
3.8
168 (32.7)
2.7
1.4 ( )
0.0008**
15 – 19
38 (5.0)
0.6
37 (7.2)
0.5
1.2 ( )
0.8084
> 19**
56 (7.4)
0.12
33 (6.4)
0.07
1.7 ( )
0.0059**
Total
757 (100)
1.1
513 (100)
0.7
1.6 ( )
Now, I would like to present a comparison of incidence rates by 2 year intervals (THE END OF THE 1 DOSE ERA) and (THE INITIATION OF THE 2 DOSE ERA).
All age groups, with the exception of years, there was a greater IR DURING THE END OF THE one dose ERA compared to THE INITIATION OF THE 2 dose era.
BASED ON our Relative Risk Calculations, THE RISK OF VARICELLA WAS GREATER DURING THE END OF THE ONE DOSE ERA COMPARED TO THE INITIATION OF THE 2 DOSE ERA. THE CHI-SQUARE TEST ALSO SHOWED SIGNIFICANT DECLINE IN IR during the initiation of the 2-dose era AMONG ALL AGE-GROUPS, ECXEPT YEARS OLD.
Significant decline in IR from to , P<0.05* & P<0.01**

16. Results: Varicella Breakthrough (BT) Cases by Age-Group, Antelope Valley, CA, 2005-2008
Verified BT cases also declined in compared to the number reported in Of 1270 verified cases documented from , 727 cases were breakthrough (BT). The highest breakthrough varicella cases documented among 5-9 age-groups during these 2 periods.
The overall proportion of breakthrough (BT) cases declined among all age groups by 32.3% from 414 in to 313 in Although the largest proportion of BT cases were among 5-9 age-group during these two periods, it also showed a declined by 55% from 242 to 156, respectively. The median age of BT cases also increased from 8 years in to 9 years in

17. Results: Clinical Presentation of Varicella Disease, Antelope Valley, CA, 2005-2008
n (%)
Rash Description
Maculo-papular*
472 (62.2%)
256 (69.5%)
Vesicular*
287 (36.7%)
117 (22.9%)
Max. # Lesions
<50 lesions*
403 (55.2%)
288 (62.1%)
50-250
252 (34.5%)
140 (30.1%)
>250
59 (9.2%)
30 (6.5%)
With increasing varicella doses in , the clinical presentation had a greater proportion with maculo papular presentation and fewer that reporter vesicular presentation.
With THE increasing NUMBER OF varicella vaccine doses ADMINISTERED in 07-08, a significantly greater proportion of cases had fewer THAN 50 lesion (<50 lesion).
* P <0.05

18. Conclusions (1)
Coincident with implementation of the 2 dose vaccination recommendations, varicella cases and disease incidence declined across most age groups
The most substantial IR declines were among the 5-9 and the year age group
There was a significant decline in the proportion of BT cases reported in the 2 dose versus 1 dose era
To summarize our findings-
Coincident with implementation of the 2 dose vaccination recommendations, varicella cases and disease incidence declined across most age groups. There was a 47.6 % overall decline in overall incidence from compared to
The most substantial IR declines were among 5-9 and the year age group.
There was also a significant decline in the proportion of BT cases reported in the 2 dose versus 1 dose era.
A greater proportion of reported varicella cases were described to have milder clinical presentations (cases with <50 lesions) with the introduction of the second dose recommendation.
Continued surveillance and epidemiologic studies are needed to further assess the impact of routine 2-dose varicella vaccination in children.

19. Conclusions (2)
A greater proportion of reported varicella cases were described to have milder clinical presentations (cases with <50 lesions) with the introduction of the second dose recommendation
Continued surveillance and epidemiologic studies are needed to further assess the impact of routine 2-dose varicella vaccination in children
To summarize our findings-
Coincident with implementation of the 2 dose vaccination recommendations, varicella cases and disease incidence declined across all age groups. There was a 47.6 % overall decline in overall incidence from compared to
The most substantial IR declines were among 5-9 and the year age group.
There was also a significant decline in the proportion of BT cases reported in the 2 dose versus 1 dose era.
A greater proportion of reported varicella cases were described to have milder clinical presentations (cases with <50 lesions) with the introduction of the second dose recommendation.
Continued surveillance and epidemiologic studies are needed to further assess the impact of routine 2-dose varicella vaccination in children.
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20. Study Limitations (1)
Only two years of data analyzed post- 2nd dose recommendation
Longer term data needed to establish clear incidence trends
Varicella clinical presentation is evolving and becoming increasingly mild
Could lead to missed varicella disease reports and underestimating true incidence
There are some important study limitations to consider:
1. We examined only two years of data post- 2nd dose recommendation,
Longer term data needed to establish clear incidence trends
2. Varicella disease clinical presentation is evolving and becoming increasingly milder
Mild clinical presentations could lead to missed varicella disease reports and underestimating true incidence

21. Study Limitations (2)
Varicella case definition based on clinical presentation and not laboratory confirmation
“Reporting Fatigue” among surveillance sites may result in missed disease reports
Lack of 2 dose varicella vaccination coverage data in surveillance area
We used vaccine doses administered as a proxy for 2 dose varicella vaccination coverage
Additional study limitations include:
3. Varicella case definition based on clinical presentation and not laboratory confirmation
4. “Reporting Fatigue” among surveillance sites may result in missed disease reports
We used vaccine doses administered as a proxy for 2 dose varicella vaccination coverage.

22. Acknowledgements Laurene Mascola, MD, MPH, VASP Principal Investigator
Rachel Civen, MD, MPH, VASP Co-Principal Investigator
VASP Research Staff
Christina Jackson, MPH
Karen Kuguru, MS
Michael Borquez
Michelle Armijo
Division of Viral Diseases, NCIRD, Centers for Disease Control and Prevention,
Stephanie Bialek, MD, MPH
Adrianna Lopez, MPH

23. QUESTIONS AND ANSWERS ? ? ? ? ? ? ?

24. Breakthrough Varicella Cases, Antelope Valley, CA, 2000-2008