276 | www.pidj.com The Pediatric Infectious Disease Journal • Volume 33, Number 3, March 2014
Background: Routine childhood varicella vaccination, implemented in
1995, has resulted in significant declines in varicella-related hospitaliza-
tions in the United States. Varicella hospitalization rates among the Ameri-
can Indian (AI) and Alaska Native (AN) population have not been previ-
Methods: We selected varicella-related hospitalizations, based on a pub-
lished definition, from the Indian Health Service inpatient database for AI/
ANs in the Alaska, Southwest and Northern Plains regions (1995–2010)
and from the Nationwide Inpatient Sample for the general US population
(2007–2010). We analyzed average annual hospitalization rates prevaccine
(1995–1998) and postvaccine (2007–2010) for the AI/AN population, and
postvaccine for the general US population.
Results: From 1995–1998 to 2007–2010, the average annual varicella-
related hospitalization rate for AI/ANs in the 3 regions decreased 95%
(0.66–0.03/10,000 persons); the postvaccine rate appears lower than the gen-
eral US rate (0.06, 95% confidence interval: 0.05–0.06). The rate declined in
all AI/AN pediatric age groups. Infants experienced the highest prevaccine
(14.07) and postvaccine (0.83) hospitalization rates. Adults experienced low
rates in both periods. Varicella vaccination rates in 19- to 35-month-old AI/
AN children during fiscal years 2008–2010 were 88.1–91.0%.
Conclusions: Widespread use of varicella vaccine in AI/AN children was
accompanied by substantial declines in varicella-related hospitalizations
consistent with high varicella vaccine effectiveness in preventing severe
Key Words: American Indian, Alaska Native, varicella, children,
(Pediatr Infect Dis J 2014;33:276–279)
varicella vaccination program, implemented as a 1-dose childhood
n the prevaccine era, varicella resulted in >10,000 hospitaliza-
tions and 100–150 deaths in the United States every year. The US
vaccine program in 1995, resulted in decreased varicella incidence,
hospitalizations and mortality in the United States.1–8 Varicella-
related hospitalization rates decreased significantly by 71% from
0.42 [95% confidence interval (CI): 0.33–0.50] per 10,000 popu-
lation in the prevaccination era (1988–1995) to 0.12 per 10,000
population in the 1-dose varicella vaccine era (2000–2006), with
declines continuing during the 2000–2006 period.1 In 2007, a sec-
ond dose of varicella vaccine was recommended by the Advisory
Committee on Immunization Practice to further decrease varicella
disease and complications.9
For certain infectious diseases including pertussis,10
Haemophilus influenzae infections, invasive pneumococcal dis-
ease11 and lower respiratory tract infection,12 American Indian (AI)
and Alaska Native (AN) child populations have higher disease bur-
den than other US child populations; however, there are no reports
on varicella disease burden or the impact of the varicella vaccina-
tion program in AI/AN populations. To address this, we analyzed
varicella-related hospitalization rates among AI/AN people before
and after implementation of routine childhood varicella vaccina-
tion and compared the rate of varicella-related hospitalization for
the most recent postvaccine period (2007–2010) with that for the
general US population.
MATERIALS AND METHODS
We performed a retrospective analysis of varicella-related
hospital discharge data for 1995–2010 among AI/AN persons using
Indian Health Service (IHS) direct and contract health service inpa-
tient data obtained from the IHS through the National Patient Infor-
mation Reporting System.13 The IHS data consist of all hospital
discharge records reported from IHS-operated and tribally oper-
ated hospitals and facilities and community hospitals and facili-
ties which are contracted with the IHS or with specific tribes to
provide healthcare services to eligible AI/AN persons.14 The IHS is
divided into 12 administrative areas.15 The California and Portland
administrative areas were excluded from this study because neither
had any IHS-operated or tribally operated hospitals.14 The Nash-
ville and Oklahoma administrative areas in the East and Southern
Plains regions, respectively, were excluded from the present study
because very few varicella-related hospitalizations were reported in
these regions—this likely reflects a greater proportion of varicella-
related hospitalizations that occur outside the IHS/tribal system in
those regions because few IHS/tribal inpatient facilities exist there.
The present study focused on the remaining IHS administrative
areas that were collapsed into 3 regions: Northern Plains (Aber-
deen, Bemidji and Billings), Alaska and Southwest (Albuquerque,
Navajo, Phoenix and Tucson). The average annual percentage of the
3 regions out of the total IHS user population (includes Portland
and California) for the period (1995–2010) is 63.87%.
We analyzed varicella-related hospitalizations in the AI/AN
population in the Northern Plains, Alaska and Southwest regions
during four 4-year periods between 1995 and 2010. We consid-
ered 1995–1998 as the prevaccine varicella period because vari-
cella vaccine uptake during this period was low [the 1998 National
Copyright © 2013 by Lippincott Williams & Wilkins
Impact of Varicella Vaccination on Varicella-related
Hospitalizations Among American Indian/Alaska Native People
Rosalyn J. Singleton, MD, MPH,* Robert C. Holman, MS,† Marissa K. Person, MSPH,†
Claudia A. Steiner, MD,‡ John T. Redd, MD,§ Thomas W. Hennessy, MD,¶ Amy Groom, MPH,‖
Stephen Holve, MD,** and Jane F. Seward, MB BS, MPH††
Accepted for publication September 19, 2013.
From the *Alaska Native Tribal Health Consortium, Anchorage, AK; †Division
of High-Consequence Pathogens and Pathology, National Center for Emerg-
ing and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Con-
trol and Prevention (CDC), U.S. Department of Health and Human Services
(USDHHS), Atlanta, GA; ‡Healthcare Cost and Utilization Project, Center
for Delivery, Organization and Markets, Agency for Healthcare Research
and Quality, USDHHS, Rockville, MD; §Indian Health Service (IHS),
USDHHS, Santa Fe, NM; ¶Arctic Investigations Program, NCEZID, CDC,
USDHHS, Anchorage, AK; ‖Immunization Services Division, CDC, USA
USDHHS, Atlanta, GA; **Tuba City Regional Health Care, IHS, USDHHS,
Tuba City, AZ; and ††Division of Viral Diseases, National Center for Immu-
nization and Respiratory Disease, CDC, GA.
The authors have no funding or conflicts of interest to disclose.
Address for Correspondence: Rosalyn Singleton, MD; AIP-CDC, 4055 Tudor
Centre Dr, Anchorage, AK 99508. E-mail: firstname.lastname@example.org.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of
this article on the journal’s website (www.pidj.com).
The Pediatric Infectious Disease Journal • Volume 33, Number 3, March 2014 Varicella Hospitalizations
© 2013 Lippincott Williams & Wilkins www.pidj.com | 277
Immunization Survey reports that AI/AN children, 19–35 months
of age, had a low rate of 1 dose of varicella vaccine (28.0+8.0) com-
pared with the general US child population (43.2+1.0)],16 and the
most recent post vaccine period as 2007–2010. Hospital discharge
records were examined by age group, sex and region. Average
annual varicella-related hospitalization rates (per 10,000 persons)
were calculated using the annual IHS regional user population
estimates as denominators for the corresponding 3 AI/AN regional
populations; the denominators for 2001–2010 were the fiscal year
(FY) 2001–2010 IHS user populations and those for 1995–2000
were annual estimates that are based on the FY 2001 user popula-
tion adjusted by the percentage change in the corresponding annual
number of eligible AI/ANs (IHS service population).14 The user
population includes all registered AI/AN persons who received
IHS-funded health care at least once within the preceding 3 years.
The average annual hospitalization rates for the 1995–1998 and
2007–2010 periods were compared overall and by age group using
Poisson regression analysis to determine rate ratios (RRs) and 95%
CI.17 Poisson regression analysis was also used to test for trend over
the 4 average annual hospitalization rates within the study period.
Statistical significance was considered as the P < 0.05 level. The
analysis of IHS data in the present study represents AI/AN persons
in the 3 regions who received direct or contract health care through
IHS health care system within the 3 regions.
For comparison, we also analyzed varicella-related hospi-
tal discharge data in the general US population during 2007–2010
from the Nationwide Inpatient Sample (NIS), a nationally repre-
sentative database of hospitalizations which is produced by the
Healthcare Cost and Utilization Project in collaboration with par-
ticipating states.18,19 The NIS is the largest all-payer inpatient data-
set in the United States and includes a 20% representative sample
of US community hospitals from participating states. The sample
approximates a 20% sample of all US community hospitals and
all discharges from sample hospitals are included in the database.
Hospitals are short-term, nonfederal general and specialty hospitals
sampled from up to 45 participating states. Estimates of the num-
ber of hospitalizations were calculated using the Healthcare Cost
and Utilization Project weighting methodology for the NIS.18–20
SUDAAN software was used to account for the sampling design of
the US national hospital discharge data to generate standard errors
of the hospitalization estimates.21 The average annual varicella-
related hospitalization rates with 95% CIs were calculated as the
weighted number of varicella-related hospitalizations per 10,000
persons for corresponding groups with denominators determined
from the National Center for Health Statistics bridged race popu-
lation estimates.22 The NIS does not include IHS/tribal facilities’
hospital discharge data.18
Varicella-related hospitalizations were defined using Inter-
national Classification of Diseases 9th Revision, Clinical Modifi-
cation (ICD-9-CM) codes23 as previously published.1,2 This defini-
tion was a hospitalization with a varicella diagnosis (ICD-9-CM
code 052) as 1 of 15 diagnoses without a herpes zoster diagnosis
(ICD-9-CM code 053) listed and including at least 1 of 4 criteria
(see Table, Supplemental Digital Content 1, http://links.lww.com/
INF/B714). The criteria included1 varicella as the first-listed dis-
charge code (ICD-9-CM code 052-052.9),2 any-listed, postvaricella
encephalitis (ICD-9-CM code 052.0), any-listed varicella pneumo-
nitis (ICD-9-CM code 052.1)3 or varicella in a person with an any-
listed severe immunocompromising condition consisting of HIV,
immune deficiency, transplant complication, chemotherapy, cancer4
or a first-listed potential complication of varicella and a varicella
code in any other position (see Table, Supplemental Digital Con-
tent 1, http://links.lww.com/INF/B714). The unit of analysis in the
present study is a hospitalization.
For varicella vaccine coverage rates, we used IHS quarterly
immunization data from the IHS electronic health records system
for FY 2001–2010 to report varicella vaccine uptake in AI/AN chil-
dren from these regions who received care at IHS/tribal facilities.24
Varicella vaccine 1-dose coverage in 16- to 18-month-old AI/AN
children from these regions was available for FY 2001–2010 and in
19- to 35-month-old children for FY 2008–2010.
From 1995–1998 to 2007–2010, varicella-related hospitali-
zations in AI/AN people in the Alaska, Southwest and Northern
Plains regions decreased 95% from 200 hospitalizations (average
annual rate 0.66/10,000 persons) during 1995–1998 to 11 hospitali-
zations (0.03; RR: 0.04, 95% CI: 0.02–0.08) in 2007–2010 (Table,
Supplemental Digital Content 1, http://links.lww.com/INF/B714).
The 2007–2010 average annual hospitalization rate for AI/AN peo-
ple appears lower than that for the general US population (0.06,
95% CI: 0.05–0.06), although the rate in < 1-year-old AI/AN infants
remains slightly higher than that for the general US infant popula-
tion. Rate declines occurred in all pediatric AI/AN age groups (P <
0.01); the declines were nonsignificant in adult AI/AN age groups.
The number and average annual rate of varicella-related hospitaliza-
tions for 2007–2010 was low in all AI/AN age groups.
AI/AN infants (<1 year of age) experienced the highest var-
icella-related average annual age-specific hospitalization rate for
the prevaccine period (14.07; P < 0.01); the rate declined 94% to a
postvaccine period rate of 0.83 (Table 1). The low rates in older AI/
AN age groups were unstable due to small numbers. AI/AN adults
(≥20 years of age) experienced a low hospitalization rate in the
prevaccine (0.05) period; numbers were too low to provide rates in
this age group for 2007–2010 (Table 1). The varicella-related aver-
age annual hospitalization rate declined by period from 1995–1998
to 2007–2010 (P < 0.01; Figure, Supplemental Digital Content 2,
Varicella-related average annual hospitalization rates were
similar among AI/AN males (0.73) and females (0.59) in the pre-
vaccine period (RR: 1.25, 95% CI: 0.94–1.64). AI/AN numbers
were too low to measure sex-specific rates in the postvaccine period
2007–2010 (Table 1). The AI/AN people in the Alaska (0.83)
region experienced higher prevaccine varicella-related hospitaliza-
tion rates compared with the Northern Plains (0.53) region (RR:
1.56, 95% CI: 1.01–2.40) and was similar to the Southwest region
(RR: 1.22, 95% CI: 0.84–1.78). The 1999–2002 postvaccine rate
in the Alaska region was higher than those for the other 2 regions
(RR: 7.74, 95% CI: 3.52–17.04 and RR: 1.79, 95% CI: 1.14–2.82,
respectively); the numbers were too low in the last 2 period to com-
pare the regions.
Varicella coverage data from IHS or AI/AN children receiv-
ing care at IHS/tribal facilities are not available before FY 2001.
From FY 2001 to FY 2010 receipt of at least 1 dose of varicella vac-
cine in 16- to 18-month-old AI/AN children from Alaska, South-
west and Northern Plains regions increased from 42.9% to 75.5%.24
During FY 2008–2010, documentation of receipt of at least 1 dose
of varicella vaccine in 19- to 35-month-old AI/AN children from
these regions ranged from 88.1% to 91.0%.24
For the first time, the dramatic impact of the varicella
vaccination program in reducing severe varicella morbidity is
described among AI/AN people, a population at risk of higher
burden from infectious diseases.10–12 These findings confirm and
extend previous reports of declines in varicella-related hospitali-
zations in the general US population and in sentinel surveillance
Singleton et al The Pediatric Infectious Disease Journal • Volume 33, Number 3, March 2014
278 | www.pidj.com
© 2013 Lippincott Williams & Wilkins
sites,1–6 by demonstrating a decline in the rate of varicella-associ-
ated hospitalizations to a lower level than that described to date.1
This rate decrease is consistent with the high vaccine coverage
achieved in young children in this population and the very high
effectiveness of the varicella vaccine in preventing severe vari-
cella outcomes and mirrors >95% declines in varicella-associ-
ated deaths among persons <50 years of age in the United States
by 2007.7,25 Declines in varicella-related hospitalization rates
occurred in all AI/AN pediatric age groups, including infants,
who are too young to be vaccinated, and appear to have declined
for adults who likely have low rates of vaccination. This demon-
strates significant indirect vaccination or herd immunity effects.
Although there was a higher burden of varicella hospitalizations
in AI/AN people in the prevaccine compared with the general
US population, the varicella-related average annual hospitaliza-
tion rate during the postvaccine period of 2007–2010 in AI/AN
people appeared lower than that of the general US population
demonstrating an elimination in this health inequity due to the
Although limited data from the prevaccine era showed
levels of acquisition of varicella antibodies in Navajo children
similar to US children,26 data are not available on patterns of
varicella acquisition in early childhood, including infancy, nor
have data on severe varicella disease burden or mortality among
AI/AN people been previously reported.26,27 The present study
describes an overall varicella-related hospitalization rate during
the 1995–1998 prevaccine period for AI/AN people that appears
to have been higher than the prevaccination hospitalization rate
estimate for the US general population from 1988 to 1995 (0.4,
95% CI: 0.3–0.5).1 In particular, the prevaccine varicella hospi-
talization rate among AI/AN infants was >3 times higher than the
prevaccine rates (1988–1995) reported for the general infant US
population (3.1).1,2 This disparity in rates among AI/AN infants
reflects a similar pattern of disparity in AI/AN infants versus the
general US infant population as described for most infectious
diseases hospitalizations.10,12,28–30 For example, in 2006–2008, the
lower respiratory tract infection hospitalization rate was 2-fold
higher in AI/AN infants than that in the general US infant popula-
tion.12 Although data on varicella-related, age-specific incidence
in this population are lacking, the higher hospitalization rate in
infants may reflect a higher disease incidence from earlier expo-
sures and/or greater disease severity. Likely factors for the higher
rates of infectious illnesses include household crowding and lack
of indoor plumbing that are common in many AI/AN commu-
nities but especially in the IHS Alaska and Southwest regions.31
This is especially germane to varicella-related hospitalizations for
skin infections complicating varicella infection.31 The low hos-
pitalization rate in AI/AN adults compared with the general US
adult population, even in the prevaccine era, is consistent with
low disease incidence and susceptibility among AI/AN adults
compared with the general US population.
The IHS/tribal data have some important limitations that
should be considered when interpreting our findings. First, these
data do not include hospitalizations among AI/AN people from
these regions that occur outside the IHS/tribal services in non-IHS
or noncontract facilities.13 Second, the population denominator is
an estimate of the number of AI/AN people within the IHS/tribal
healthcare system and may not include all eligible AI/AN people.
The AI/AN people, and the corresponding rates, in the present
study might not be representative of all AI/AN people in the United
States. Third, we used IHS vaccine coverage rates for AI/AN 16-
to 18-month-old and 19- to 35-month-old children as a surrogate
for childhood vaccination coverage among all children. Fourth, by
defining 1995–1998 as prevaccine, we may have underestimated
decline in disease since estimates from the National Immunization
Survey show that an estimated 28.0 ± 8.0% of 19- to 35-month-old
AI/AN children in the United States had received varicella vaccine
by the end of 1998.16 Lastly, we were unable to examine the health
status of persons who were hospitalized with varicella in the post-
vaccine era to assess presence of underlying medical conditions or
medications that may have precluded vaccination.
We thank all of the staff at the participating IHS/tribal facilities,
as well as Barbara Strzelczyk (IHS) for technical assistance. We also
thank the State data organizations that voluntarily contribute their
hospitalization data to the Healthcare Cost and Utilization Project
to create the Nationwide Inpatient Database.
1. Lopez AS, Zhang J, Brown C, Bialek S. Varicella-related hospitalizations
in the United States, 2000–2006: the 1-dose varicella vaccination era.
2. Galil K, Brown C, Lin F, Seward J. Hospitalizations for varicella in the
United States, 1988 to 1999. Pediatr Infect Dis J. 2002;21:931–935.
3. Chaves SS, Lopez AS, Watson TL, et al. Varicella in infants after imple-
mentation of the US varicella vaccination program. Pediatrics. 2011;128:
4. Davis MM, Patel MS, Gebremariam A. Decline in varicella-related hos-
pitalizations and expenditures for children and adults after introduction of
varicella vaccine in the United States. Pediatrics. 2004;114:786–792.
5. Reynolds MA, Watson BM, Plott-Adams KK, et al. Epidemiology of vari-
cella hospitalizations in the United States, 1995–2005. J Infect Dis. 2008;
197 (suppl 2):S120–S126.
6. Shah SS, Wood SM, Luan X, et al. Decline in varicella-related ambulatory
visits and hospitalizations in the United States since routine immunization
against varicella. Pediatr Infect Dis J. 2010;29:199–204.
7. Marin M, Zhang JX, Seward JF. Near elimination of varicella deaths
in the US after implementation of the vaccination program. Pediatrics.
8. Nguyen HQ, Jumaan AO, Seward JF. Decline in mortality due to varicella
after implementation of varicella vaccination in the United States. N Engl J
9. Centers for Disease Control and Prevention. Prevention of varicella: recom-
mendations of the advisory committee on immunization practices. MMWR.
10. Murphy TV, Syed SB, Holman RC, et al. Pertussis-associated hospi-
talizations in American Indian and Alaska Native infants. J Pediatr.
11. Weatherholtz R, Millar EV , Moulton LH, et al. Invasive pneumococcal disease
a decade after pneumococcal conjugate vaccine use in an American Indian
population at high risk for disease. Clin Infect Dis. 2010;50:1238–1246.
12. Singleton RJ, Holman RC, Folkema AM, et al. Trends in lower respiratory
tract infection hospitalizations among American Indian/Alaska Native chil-
dren and the general US child population. J Pediatr. 2012;161:296–302.e2.
13. Indian Health Service. Direct/CHS Inpatient data, Fiscal Years 1995–2011,
National Patient Information Reporting System. Albuquerque, NM: Indian
Health Service; 2012.
14. Indian Health Service. Trends in Indian Health, 2002–2003. Rockville, MD:
Indian Health Service; 2009.
15. Indian Health Service. Indian health service area offices webpage. March
2013. Available at: http://www.ihs.gov/locations/. Accessed December 16,
16. Centers for Disease Control and Prevention. National immunization survey
data tables, 1998. Available at: http://www.cdc.gov/vaccines/stats-surv/nis/
data/tables_1998.htm. Accessed April 2012.
17. Kleinbaum DG, Kupper LL, Muller KE, et al. Applied Regression Analysis
and Multivariable Methods. 3rd ed. Pacific Grove (CA): Duxbury Press;
18. HCUP NIS Database Documentation. Healthcare cost and utilization pro-
ject (HCUP). Available at: www.hcup-us.ahrq.gov/db/nation/nis/nisdbdocu-
mentation.jsp. Accessed February 2013.
19. HCUP Databases. Healthcare cost and utilization project (HCUP). Available
at: www.hcup-us.ahrq.gov/databases.jsp. Accessed February, 2013.
The Pediatric Infectious Disease Journal • Volume 33, Number 3, March 2014 Varicella Hospitalizations
© 2013 Lippincott Williams & Wilkins www.pidj.com | 279
20. Houchens R, Elixhauser A. A Final report on calculating Nationwide
Inpatient Sample (NIS) variances, 2001. In: #2003-2 HMSR, ed. U.S.
Agency for Healthcare Research and Quality, June 6, 2005.
21. Research Triangle Institute. SUDAAN Users Manual, Release 10. Research
Triangle Park, NC: Research Triangle Institute; 2008.
22. National Center for Health Statistics Website. Estimates of the July 1, 2000-
July 1, 2010, United States resident population from the Vintage 2010 post-
censal series by year, county, single-year of age (0,1,2,…,85 years and over),
bridged race, Hispanic origin, and sex, prepared under a collaborative agree-
ment with the U.S. Census Bureau. Available at: http://www.cdc.gov/nchs/
about/major/dvs/popbridge/popbridge.htm. Accessed June 6, 2012.
23. Public Health Service and Health Care Financing Administration. International
Classification of Diseases, 9th revision, Clinical Modification. 6th ed.
Washington DC: US Department of Health and Human Services; 2008.
24. Indian Health Service, Division of Epidemiology and Disease Prevention.
Immunization coverage reports. Available at: http://www.ihs.gov/Epi/index.
cfm?module=epi_vaccine_reports. Accessed March 1, 2013.
25. Seward JF, Marin M, Vázquez M. Varicella vaccine effectiveness in the US
vaccination program: a review. J Infect Dis. 2008;197 (suppl 2):S82–S89.
26. Becker TM, Magder L, Harrison HR, et al. The epidemiology of infec-
tion with the human herpesviruses in Navajo children. Am J Epidemiol.
27. Kilgore PE, Kruszon-Moran D, Seward JF, et al. Varicella in Americans
from NHANES III: implications for control through routine immunization.
J Med Virol. 2003;70 (suppl 1):S111–S118.
28. Singleton RJ, Holman RC, Yorita KL, et al. Diarrhea-associated hospitali-
zations and outpatient visits among American Indian and Alaska Native
children younger than five years of age, 2000–2004. Pediatr Infect Dis J.
29. Holman RC, Curns AT, Cheek JE, et al. Infectious disease hospitaliza-
tions among American Indian and Alaska native infants. Pediatrics.
30. Holman RC, Curns AT, Cheek JE, et al. Respiratory syncytial virus hospital-
izations among American Indian and Alaska Native infants and the general
United States infant population. Pediatrics. 2004;114:e437–e444.
31. Hennessy TW, Ritter T, Holman RC, et al. The relationship between in-home
water service and the risk of respiratory tract, skin, and gastrointestinal tract
infections among rural Alaska Natives. Am J Public Health 2008;98:1–7.
Systematic Review of the Effect of Pneumococcal Conjugate Vaccine Dosing Schedule on Immunogenicity: ERRATUM
In the article appearing on page S119 of volume 33, issue 1, supplement 2, the fourth author’s name is incorrect. The author should
appear as Subhash Chandir, PhD.
Deloria Knoll M, Park DE, Johnson TS, et al. Systematic review of the effect of pneumococcal conjugate vaccine dosing schedule on immunogenicity. Pediatr
Infect Dis J. 2013;33(suppl 2):S119–129.