Varicella mortality trends before vaccine licensure in the united states, 1970–1994Document Transcript
Varicella Mortality: Trends before Vaccine Licensure in the United States,
Pamela A. Meyer,1,a
Jane F. Seward,2
Aisha O. Jumaan,2
and Melinda Wharton2
Council of State and Territorial Epidemiologists and 2
Immunization Program, Centers for Disease Control and Prevention,
We examined varicella deaths in the United States during the 25 years before vaccine li-
censure and identiﬁed 2262 people who died with varicella as the underlying cause of death.
From 1970 to 1994, varicella mortality declined, followed by an increase. Mortality rates were
highest among children; however, adult varicella deaths more than doubled in number, pro-
portion, and rate per million population. Despite declining fatality rates, in 1990–1994, adults
had a risk 25 times greater and infants had a risk 4 times greater of dying from varicella than
did children 1–4 years old, and most people who died of varicella were previously healthy.
Varicella deaths are now preventable by vaccine. Investigation and reporting of all varicella
deaths in the United States is needed to accurately document deaths due to varicella, to
improve prevention efforts, and to evaluate the vaccine’s impact on mortality.
Varicella is a highly infectious disease that is preventable by
vaccine. Before vaccine licensure in 1995, ∼4 million cases per
year resulted in р9300 hospitalizations  and 100 deaths each
year . Children bore the brunt of the health burden, accounting
for 190% of cases, 66% of hospitalizations, and 45% of deaths
(Centers for Disease Control and Prevention [CDC],unpublished
data); however, the risk of severe complications and death was
highest among infants, adults , and immunocompromised in-
dividuals [3, 4]. Moreover, complications and deaths were de-
scribed commonly among previously healthy individuals [5–9].
Use of the varicella vaccine, which is recommended for rou-
tine use among susceptible people 112 months old [10, 11], is
anticipated to alter the epidemiology of varicella by shifting
the largest proportion of cases from children to adults. High
vaccine coverage in childhood, especially if combined with a
catch-up immunization program at adolescence, is expected to
lead to a dramatic overall reduction in varicella cases and com-
plications among both children and adults .
There has been no long-term, comprehensive analysis of vari-
cella mortality for all age groups in the United States. We, there-
fore, analyzed national mortality data to characterize varicella
deaths among United States residents during 1970–1994, the 25-
year period before varicella vaccine licensure. These data will
serve as baseline data for an evaluation of the impact of the
vaccination program on varicella mortality in the United States.
Received 14 February 2000; revised 21 April 2000; electronicallypublished
12 July 2000.
Present afﬁliation: National Center for Environmental Health, Centers
for Disease Control and Prevention, Atlanta, Georgia.
Reprints or correspondence: Dr. Jane F. Seward, National Immunization
Program, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE,
Mailstop E-61, Atlanta, GA 30333 (email@example.com).
The Journal of Infectious Diseases 2000;182:383–90
᭧ 2000 by the Infectious Diseases Society of America. All rights reserved.
Sources of mortality data. We focused on the 25 years before
vaccine licensure because there is a 2-year delay in the availability
of national mortality public-use data (e.g., 1997 is now available)
and because it is too early to evaluate the impact of the varicella
vaccination program, which became operational in most state
health departments by the end of 1996. We analyzed death records
for 1970–1994 in the national Multiple Cause Mortality Database,
which is maintained by CDC’s National Center for Health Statis-
tics (NCHS). The Multiple Cause Mortality Database includes all
deaths in the United States, except for 3 years (1972, 1981, and
1982). In 1972, only 50% of deaths were coded for underlying cause
of death, and in 1981 and 1982, only 50% of deaths were coded
for multiple conditions in 19 of 50 states. To estimate the actual
national deaths, NCHS duplicated records for 1981–1982 in the
public-use ﬁles, and we duplicated 1972 records for this study.
The cause or causes of death obtained from death records were
coded according to the Eighth Revision International Classiﬁcation
of Diseases, Adapted for Use in the United States (ICD-8A) 
for 1968–1978 and according to the 9th revision of the International
Classiﬁcation of Diseases (ICD-9)  for 1979–1994. The under-
lying cause of death is determined by a computer algorithm that
evaluates all the codes for cause of death . The algorithm assigns
an underlying cause of death on the basis of conditions and their
positions as listed on the death certiﬁcates. We analyzed deaths for
which varicella (ICD-8A code 0.52 and ICD-9 code 0.52) was de-
termined to be the underlying cause of death for consistency with
ofﬁcial death statistics reported from NCHS. The algorithm for
assigning varicella as the underlying cause of death and the in-
structions for using the varicella codes were the same throughout
the study period.
Preexisting conditions and complications. We deﬁned preexist-
ing conditions as conditions listed on the death record that were
likely to have existed before the varicella infection and classiﬁed
them according to their potential to increase the risk for severe
varicella infection. High-risk conditions were deﬁned as those for
which the Advisory Committee on Immunization Practices does
384 Meyer et al. JID 2000;182 (August)
Table 1. Eighth Revision International Classiﬁcation of Diseases, Adapted for Use in the United States
(ICD-8A)  and Ninth Revision International Classiﬁcation of Diseases (ICD-9)  codes.
complication ICD-8A ICD-9
High-risk preexisting conditions
Malignancies 140.0–163.9; 170.0–174.0; 180.0–209.0 140.0–165.9; 170.0–175.0; 179.0–208.9
Immune deﬁciency 275.0–275.1 279.0–279.9
— 042.0–044.9, 795.8
Central nervous system
347.9, 780.4, 065.0, 323.0, 781.7,
320.8, 320.9, 045.9, 347.9
334.3, 334.9, 781.3, 049.9, 323.8,
323.9, 348.3, 047.8, 047.9,
286.4–286.5, 287.0–287.2, 287.9 286.6, 286.9, 287.0–287.5, 287.9
034.1, 035.0, 039.0–039.9, 732.0,
680.0–684.0, 686.0, 686.9,
038.0–038.9, 322.0, 324.0
034.1, 035, 040.0–040.9, 041.0–041.9,
729.4, 420.0–420.9, 421.0–421.9,
429.0, 320.1–320.3, 320.8–320.9,
680.0–684.0, 686.0, 686.8–686.9,
038.0–038.9, 790.7, 324.0, 324.1,
481.0–482.3, 482.9, 480.0, 486.0,
481.0, 480.8, 480.9, 486.0, 483.0,
Cerebral ataxia, encephalitis, myelitis, encephalopathy, encephalomyelitis, meningitis, other diseases of brain
(ICD-8A includes Reye’s syndrome), cerebral degeneration, and other (ICD-9 includes Reye’s syndrome).
Purpura, thrombocytopenia, and other hemorrhagic conditions.
Other bacterial infections, infective myositis and other inﬂammatory diseases of tendon and fascia, endocarditis,
pericarditis, bacterial meningitis, skin infections, cellulitis, impetigo, septicemia, and intracranial/intraspinal abscess.
Bacterial, viral, organism unspeciﬁed, other, and bronchopneumonia.
Figure 1. Percentage of varicella deaths, by month of death and age
group, United States, 1970–1994.
not recommend vaccine administration because of the risk of severe
varicella disease in the vaccine recipient—for example, malignan-
cies and AIDS (comprising human immunodeﬁciency virus [HIV]/
AIDS). We searched death records for additional conditions that
may increase the risk for severe varicella infection either due to the
underlying condition or to treatment for the condition (e.g.,
asthma, systemic lupus erythematosus, cystic ﬁbrosis, rheumatoid
arthritis and allied conditions, diabetes, and scleroderma). Because
of the low proportion of these potentially moderate risk conditions
(2.7%) over the 25-year period, we analyzed them with death re-
cords of the previously healthy—that is, those that did not list any
of the high-risk preexisting conditions (table 1).
We deﬁned varicella-associated complications as conditions listed
on the death record that were likely to have occurred as a conse-
quence of varicella infection. We focused on 4 categories: pneumonia,
central nervous system (CNS) complications, hemorrhagic condi-
tions, and secondary infections. Pneumonia was deﬁned as either
viral or bacterial pneumonia. CNS complicationsincludedconditions
that affected the CNS as a direct consequence of varicella infection,
such as encephalitis, cerebellar ataxia, and Reye’s syndrome. Hem-
orrhagic conditions included purpura and thrombocytopenia. Sec-
ondary infections were deﬁned as bacterial infections, includingthose
that affect the CNS, such as brain abscess (table 1).
Data analysis. Analyses were performed with SAS statistical
software, version 6.12 (SAS Institute, Cary, NC). We deﬁned chil-
dren as people р19 years old and adults as people у20 years old.
Neonatal deaths included infants !28 days old. We assessed sea-
sonality by examining the number and percentage of varicella
deaths, by age group and by month of death. We examined sea-
sonality for all years and for the unduplicated years, to determine
if duplicating records distorted ﬁndings; however, the results were
similar, so we present seasonality for all years. To calculate varicella
death rates for the foreign-born population, we used the deaths
for 1980–1994 (the only complete 5-year intervals for which for-
eign-born status was recorded on the death records) and applied
the foreign-born population estimates obtained from the Census
Bureau’s current population reports for 1980 and 1990 . To
account for changes in the population age distribution over the 25-
year period, we calculated age-adjusted varicella mortality rates by
making use of the estimated United States year 2000 population
. For calculation of case-fatality rates (CFR), we estimated the
number of varicella cases by using the 1970–1994 National Health
Interview Surveys , which are maintained by NCHS. The Na-
tional Health Interview Surveys collect information on health-re-
lated issues by conducting personal interview surveys annually and
uses a nationwide sample of the civilian, noninstitutionalizedpopu-
lation in the United States. We calculated age-speciﬁc varicella
JID 2000;182 (August) Varicella Deaths in the United States, 1970–1994 385
Table 2. Number and percentage of people who died with varicella as the underlying cause
of death, by age group, sex, race, and foreign-born status for all years and for each 5-year
interval, United States, 1970–1994.
(n p 2262)
(n p 555)
(n p 471)
(n p 335)
(n p 376)
(n p 525)
!1 year 187 (8.2) 60 (10.8) 28 (6.0) 20 (6.0) 35 (9.3) 44 (8.4)
1–4 years 335 (14.8) 118 (21.3) 76 (16.1) 37 (11.0) 38 (10.1) 66 (12.6)
5–9 years 560 (24.8) 216 (38.9) 138 (29.3) 70 (20.9) 58 (15.4) 78 (14.8)
10–14 years 175 (7.7) 46 (8.3) 44 (9.3) 36 (10.7) 20 (5.3) 29 (5.5)
15–19 years 78 (3.5) 4 (0.7) 16 (3.4) 10 (3.0) 25 (6.7) 23 (4.4)
у20 years 927 (41.0) 111 (20.0) 169 (35.9) 162 (48.4) 200 (53.2) 285 (54.3)
Female 1105 (48.9) 291 (52.4) 231 (49.0) 165 (49.2) 170 (45.2) 248 (47.2)
Male 1157 (51.1) 264 (47.6) 240 (51.0) 170 (50.8) 206 (54.8) 277 (52.8)
African American 157 (6.9) 57 (10.3) 33 (7.0) 17 (5.1) 14 (3.7) 36 (6.9)
White 1895 (83.8) 488 (87.9) 425 (90.2) 285 (85.0) 304 (80.9) 393 (74.8)
Other 210 (9.3) 10 (1.8) 13 (2.8) 33 (9.9) 58 (15.4) 96 (18.3)
!20 years NA NA NA 5 (1.5) 10 (2.7) 11 (2.1)
у20 years NA NA NA 35 (10.4) 43 (11.4) 62 (11.8)
!20 years NA NA NA 167 (49.9) 166 (44.1) 229 (43.6)
у20 years NA NA NA 126 (37.6) 155 (41.2) 222 (42.3)
!20 years NA NA NA 1 (0.3) 0 (0.0) 0 (0.0)
у20 years NA NA NA 1 (0.3) 2 (0.6) 1 (0.2)
NOTE. Data are no. (%). NA, not applicable.
incidence rates for each of the 5-year periods and multiplied those
rates by the averaged United States population for the appropriate
age group and 5-year period.
From 1970 to 1994, 2262 death records listed varicella as the
underlying cause of death, an average of 90 deaths per year;
these ranged from 47 deaths in 1986 to 138 in 1973. Table 2
shows the demographic characteristics of decedents whose un-
derlying cause of death was varicella. For the 25-year period,
most deaths occurred among children (59.0%) and whites
(83.8%). Adults 150 years old accounted for 19.1% of all vari-
cella deaths, and infants !28 days old accounted for 1.2% of
all varicella deaths. There was a shift in the age distribution of
varicella deaths from children (80.0%) in 1970–1974 to adults
(54.3%) in 1990–1994. Whites accounted for most varicella
deaths during the study period; however, the proportion of
deaths among decedents of races other than white or African
American increased from 1.8% to 18.3% during the 25-year
period. Foreign-born status was available only for the 5-year
intervals from 1980–1984 through 1990–1994. Of the 166 for-
eign-born decedents in these years, 84.3% were у20 years old.
Seasonality. Varicella deaths showed a strong seasonal pat-
tern consistent with patterns for varicella cases. Overall, 44.2%
of deaths occurred between March and May and 8.4% occurred
between August and October. Figure 1 shows a seasonal pattern
in all age groups, but the pattern was less pronounced among
adults у50 years old, compared with adults 20–49 years old
and children !20 years old. There was a strong seasonal pattern
for deaths regardless of the presence or absence on the death
record of a high-risk preexisting medical condition.
Varicella mortality rates. Varicella mortality rates have been
consistently higher among children !15 years old than among
adults; the highest rates occurred among infants !12 months old.
The overall varicella mortality rate showed a pattern of decline
followed by an increase (ﬁgure 2). The pattern of change in
mortality rates differed by age group (table 3). Mortality rates
among children !10 years old declined through the 1970s and
early 1980s, with the greatest decline among children 5–9 years
old, but they then increased in the late 1980s and early 1990s.
In contrast to the overall decline in mortality rates among
children from 1970–1974 to 1990–1994, mortality rates have in-
creased among adults, neonates, and foreign-bornadultresidents.
Adult mortality rates increased 83% from 0.17 per million pop-
ulation during 1970–1974 to 0.31 per million population during
1990–1994. Among neonates, the varicella mortality rate in-
creased from 0.59 per million live births in 1970–1974 to 2.47 in
1990–1994. There also has been an increase in age-speciﬁc var-
icella mortality rates among foreign-born residents. During
1980–1984, when information on place of birth became available,
mortality rates were higher among foreign-born than among
United States–born residents who were у45 years old (3.48 vs.
1.06) and among those 20–44 years old (2.36 vs. 0.74), but not
among those !20 years old (2.36 vs. 2.38). Mortality rates in-
creased among both foreign-born and United States–born resi-
386 Meyer et al. JID 2000;182 (August)
Figure 2. Varicella mortality rates (age-adjusted to year 2000 pop-
ulation), United States, 1970–1994.
Table 3. Five-year average varicella mortality rates, by age group,
sex, and race, United States, 1970–1994.
!1 year 3.61 1.72 1.11 1.84 2.24
1–4 years 1.73 1.21 0.54 0.52 0.86
5–9 years 2.29 1.59 0.86 0.67 0.85
10–14 years 0.44 0.45 0.40 0.24 0.32
15–19 years 0.40 0.15 0.10 0.27 0.26
у20 years 0.17 0.23 0.20 0.23 0.31
Female 0.47 0.40 0.28 0.27 0.37
Male 0.46 0.43 0.31 0.35 0.45
African American 0.43 0.24 0.15 0.09 0.22
White 0.47 0.43 0.29 0.30 0.36
Other 0.53 0.64 1.33 1.50 1.68
Total 0.46 0.41 0.29 0.31 0.40
NOTE. Mortality rate is per 1,000,000 population.
Sex and race are age-adjusted to 2000 U.S. population.
dents during 1990–1994 and were consistently higher for foreign-
born residents who were у45 years old (5.11 vs. 1.16), 20–44
years old (2.58 vs. 1.56), and !20 years old (4.16 vs. 3.31).
Mortality rates have been similar for males and females
throughout the study period. Mortality rates among male pa-
tients and female patients declined through the 1970s and early
1980s, then increased for males in the late 1980s and for females
in the 1990s. Mortality rates were higher among whites than
among African Americans, and mortality rates declined in the
early 1970s and 1980s; however, rates began to increase among
African Americans in 1990–1994. Mortality rates for people in
all other racial categories combined have been higher than rates
for either whites or African Americans and have been steadily
CFR. Overall, the CFR were highest among adults, fol-
lowed by infants, with the lowest rates among children 1–4
years old, followed closely by children 5–9 years old. With the
exception of children 15–19 years old, CFR declined between
51.3%–72.2% in all age groups, with the greatest decline oc-
curring among adults. The ﬂuctuation in CFR among the
15–19-year-old children reﬂects the small numbers of deaths in
this age group. In 1990–1994, adults had a risk 25 times greater
and infants had a risk 4 times greater of dying from varicella
than did children 1–4 years old (table 4).
Preexisting conditions. Overall, 622 (27.5%) varicella death
records listed a preexisting high-risk condition; malignancies ac-
counted for 88.4% of all high-risk conditions; however, the pro-
portion of preexisting conditions varied during the study period.
Malignancies were listed on 22.5% of varicella death records in
1970–1974, 35.9% in 1975–1979, and 11.4% in 1990–1994. HIV/
AIDS codes ﬁrst appeared on varicella death records during
1985–1989. By 1990–1994, HIV/AIDS was listed on 2.1% of
varicella death records for children р19 years old, 13.5% for
those 20–49 years old, and 2.8% for people 150 years old. Most
varicella deaths occurred in previously healthy individuals, rang-
ing from 66.5% of child varicella deaths and 56.8% of adult
varicella deaths in 1980–1984 to 88.8% and 74.7% of child and
adult varicella deaths, respectively, in 1990–1994.
Complications. Overall, the most common complication
among people who died from varicella was pneumonia (27.6%),
followed by CNS complications (21.1%), secondary infections
(8.6%), and hemorrhagic conditions (4.8%). Fatal pneumonia
complications affected all age groups (range, 21.3% for 10–19-
year-olds to 32.5% for people у20 years old). Over the 25-year
period, pneumonia complications declined among people who
died from varicella, especially among decedents with preexisting
high-risk conditions, but also among decedents who were pre-
viously healthy adults (60.4%). Yet among previously healthy
children who died of varicella, the proportion with pneumonia
complications was relatively stable at ∼20% (table 5).
CNS complications occurred in 44.1% of varicella deaths in
1970–1974, but only in 5.7% in 1990–1994. CNS complications
were more common among children who died of varicella who
were !15 years of age and among decedents of all ages who
were previously healthy. Nonetheless, fatal varicella compli-
cations varied by age and risk status over time. Among children
who died of varicella who were previously healthy, the pro-
portion with CNS complications declined from 64.0% in
1970–1974 to 8.9% in 1990–1994. Although fatal CNS com-
plications were less common among previously healthy adult
decedents than among child decedents, the proportions also
declined, from 11.9% in 1970–1974 to 1.4% in 1990–1994.
Reye’s syndrome, which is included in our deﬁnition of CNS
complications, occurred almost exclusively among children !15
years old who died of varicella and declined sharply in the early
1980s. During 1970–1979, there were 170 (16.6%) varicella
deaths records that listed possible Reye’s syndrome, compared
with 28 (2.3%) during 1980–1994.
In contrast to the decline in CNS complications and pneu-
monia reported in varicella deaths over the 25 years under
study, hemorrhagic conditions and secondary infections in-
creased. Hemorrhagic conditions reported in varicella death
records increased from 2.5% in 1970–1974 to 8.0% in
JID 2000;182 (August) Varicella Deaths in the United States, 1970–1994 387
Table 4. Varicella case-fatality rate, by age group and year of death (5-year interval) and 95%
conﬁdence intervals (CIs), United States, 1970–1994.
Age, years 1970–1974 1975–1979 1980–1984 1985–1989 1990–1994
!1 7.6 (3.0–11.9) 7.2 (1.2–13.1) 5.1 (0.1–10.1) 6.8 (1.8–11.8) 3.7 (1.3–6.2)
1–4 2.3 (1.3–3.2) 1.7 (0.8–2.5) 0.7 (0.2–1.3) 0.6 (0.2–1.0) 0.8 (0.4–1.3)
5–9 2.8 (1.9–3.6) 2.0 (1.3–2.8) 1.0 (0.5–1.5) 0.7 (0.3–1.1) 1.0 (0.5–1.5)
10–14 4.2 (1.5–6.9) 2.0 (0.7–3.4) 1.6 (0.4–2.8) 0.8 (0–1.6) 1.6 (0.3–2.8)
15–19 1.0 (1.2–3.1) 4.9 (0.5–10.2) 1.4 (0.5–3.3) 4.1 (0.5–7.7) 5.9 (0.5–11.2)
76.6 (44.7–108.5) 77.4 (51.3–103.5) 17.6 (11.6–23.7) 19.5 (13.4–25.5) 21.3 (15.8–26.8)
Total 3.6 (2.9–4.2) 3.2 (2.6–3.9) 2.0 (1.5–2.5) 2.0 (1.5- 2.4) 2.6 (2.1–3.1)
NOTE. Data are deaths per 100,000 varicella cases (95% CIs). The numbers of varicella cases are estimated
from the 1970–1994 National Health Interview Surveys (NHIS). NHIS are conducted annually and use a nationwide
sample of the civilian, noninstitutionalized population in the United States.
Case-fatality rates for adults had very wide CIs during 1970–1974 and 1975–1979 because the estimates for
the number of adult varicella cases were based on responses in the NHIS and because there were few adult varicella
1990–1994, whereas secondary infections increased from 3.1%
to 13.1%, most prominently among previously healthy children.
This is the ﬁrst long-term analysis of deaths due to varicella
in the United States to describe mortality rates, CFR, com-
plications, and preexisting conditions among both child and
adult decedents. This study demonstrates important changes in
varicella mortality in the United States before the availability
of varicella vaccine. Most striking was the shift in the prepon-
derance of varicella deaths from children in the 1970s to adults
in the 1990s. During the 25-year time period under study, as
deaths declined among children, who made up the majority of
cases and deaths in the 1970s, the number of adult deaths
increased 3-fold, and, consequently, the relative proportion of
adult deaths increased. The increase in adult deaths is consistent
with data from the United Kingdom that indicate increases in
both the adult varicella mortality rate and the proportion of
varicella cases among adults [19, 20].
Increased mortality among adults may partly reﬂect in-
creased migration to the United States of people from tropical
countries, such as Mexico, the Philippines, China, Vietnam, and
India, where adults are more likely to be susceptible to varicella
. Varicella death rates were higher among adults born in
other countries, compared with adults born in the United
States. During the time when place-of-birth information was
available on the death records (1985–1994), ∼20% of all adult
varicella deaths occurred among foreign-born adults.
The increase in neonatal deaths, although relatively few in
number, contrasts with a decline in neonatal mortality in the
United Kingdom over a similar time period (1967–1990) .
The increase in neonatal deaths parallels the increase in adult
deaths, which occurred while adult CFR declined, which sug-
gests that adult varicella cases have increased in the United
States over the 25-year period. This may have resulted in more
mothers acquiring infection during pregnancy or around the
time of delivery. The increase in neonatal deaths in the United
States may be due to varicella-zoster immune globulin not being
offered appropriately to neonates whose mothers are infected
with varicella around the time of delivery. Alternatively, it could
reﬂect an increase in deaths in the neonatal period from con-
genital varicella syndrome (not identiﬁable on death records
with a speciﬁc ICD code) secondary to maternal infection dur-
ing the ﬁrst 2 trimesters of pregnancy.
The decline in mortality rates among children in the 1970s
and 1980s occurred concurrently with improved medical treat-
ment and survival of people with malignancies , effective
antiviral therapies for varicella zoster virus infections, and im-
proved treatment of life-threatening varicella complications. In
addition, reported cases of Reye’s syndrome declined dramat-
ically after publication of the association between aspirin and
Reye’s syndrome and common viral illnesses, often inﬂuenza
or varicella [24, 25].
The dramatic decline in varicella CNS complications among
child decedents paralleled decreases in reports to the CDC of
cases of postinfectious encephalitis during the late 1970s andearly
1980s  and of varicella-associated Reye’s syndrome cases 
during the 1980s. Studies conducted in the United States in the
1970s  reported higher rates of encephalitis as a complication
of varicella than those conducted in the early 1990s .Similarly,
a study in the United Kingdom reported a marked decline in
deaths due to encephalitis among children between 1967 and1985
. It is plausible that Reye’s syndrome was misdiagnosed as
encephalitis. A postmortem study of 32 children who died of
varicella during 1952–1977 found that 12 decedents had acute
encephalopathy compatible with Reye’s syndrome, but only 2
had deﬁnite encephalitis, which suggests that true encephalitis is
a rare event in fatal varicella . After CNS complications de-
clined, pneumonia became the most common lethal varicella
complication among healthy children and adults, followed by
secondary infections. The increase in secondary infectionsamong
child decedents may reﬂect a true increase in severe secondary
infections, especially invasive group A streptococcal infections,
which have been associated with varicella , or it may reﬂect
improved laboratory diagnosis.
In contrast to this decline, we are unable to explain the in-
crease in mortality that occurred among adults and children
388 Meyer et al. JID 2000;182 (August)
Table 5. Varicella complications among varicella decedents, stratiﬁed by age group, risk status, and 5-year interval, United States, 1970–1994.
!20 years old у20 years old
High-risk Healthy High-risk Healthy
Complications All deaths, n Complications All deaths, n Complications All deaths, n Complications All deaths, n
Central nervous system
1970–1974 5 (5.8) 86 229 (64.0) 358 3 (6.8) 44 8 (11.9) 67
1975–1979 6 (7.6) 79 133 (59.6) 223 5 (5.4) 93 10 (13.2) 76
1980–1984 2 (3.4) 58 24 (20.9) 115 0 (0.0) 70 2 (2.2) 92
1985–1989 2 (5.4) 37 12 (8.6) 139 2 (3.6) 56 4 (2.8) 144
1990–1994 4 (14.8) 27 19 (8.9) 213 4 (5.6) 72 3 (1.4) 213
1970–1974 42 (48.8) 86 82 (22.9) 358 23 (52.3) 44 43 (64.2) 67
1975–1979 40 (50.6) 79 48 (21.5) 223 35 (37.6) 93 36 (47.4) 76
1980–1984 15 (25.9) 58 23 (20.0) 115 18 (25.7) 70 36 (39.1) 92
1985–1989 2 (5.4) 37 27 (19.4) 139 5 (8.9) 56 45 (31.3) 144
1990–1994 3 (11.1) 27 42 (19.7) 213 6 (8.3) 72 54 (25.4) 213
1970–1974 7 (8.6) 86 7 (1.9) 358 3 (6.8) 44 0 (0.0) 67
1975–1979 8 (10.4) 79 21 (9.3) 223 5 (5.4) 93 7 (9.1) 76
1980–1984 3 (5.2) 58 12 (10.4) 115 1 (1.4) 70 5 (5.4) 92
1985–1989 4 (10.8) 37 20 (14.4) 139 8 (14.3) 56 15 (10.4) 144
1990–1994 5 (18.5) 27 35 (16.4) 213 7 (9.7) 72 22 (10.3) 213
1970–1974 3 (3.7) 86 10 (2.8) 358 1 (2.3) 44 0 (0.0) 67
1975–1979 3 (3.9) 79 4 (1.8) 223 2 (2.2) 93 0 (0.0) 76
1980–1984 1 (1.7) 58 12 (10.4) 115 1 (1.4) 70 9 (9.8) 92
1985–1989 3 (8.1) 37 10 (7.2) 139 3 (5.4) 56 4 (2.8) 144
1990–1994 1 (3.7) 27 19 (8.9) 213 4 (5.6) 72 18 (8.5) 213
NOTE. Data are no. (%), except where noted.
from the mid-1980s. Although the number of death records
that mentioned HIV/AIDS increased during this time, most
deaths occurred among otherwise healthy children and adults.
This suggests that among healthy people, there may be less
awareness of the potential severity of varicella, which could
result in delays in seeking health care, in complications not
being recognized, or in aggressive therapy for complications
not being offered as early to this group. It is also possible that
the decrease in deaths among high-risk people reﬂects health
care providers’ vigilance in administering antiviral treatment to
people with malignancies and other preexisting high-risk con-
ditions. Furthermore, high-risk conditions may have existed but
were not reported. For example, information collected fordeath
records is limited to medical conditions, with no information
provided on immune suppressive medical therapies, such as
systemic steroid use. Therefore, this study may underestimate
the number of decedents with preexisting high-risk conditions.
There are several limitations associated with using death re-
cords. These include coding errors, antemortem diagnostic er-
rors, inadvertent omissions, underreporting of preexisting con-
ditions, such as HIV infection , unavailability of medical
records to the certifying physician, death record completion
before medical workup, difﬁculty in determining the underlying
cause of death when several disease processes are involved, and
misunderstanding of the certiﬁcation process .
Three other limitations should be considered when inter-
preting the data we report. First, misclassiﬁcation may have
occurred in assigning the underlying cause of death. Misclas-
siﬁcation could result in underestimating varicella deaths if
complications of varicella, such as pneumonia or group A strep-
tococcal infections, were assigned as the underlying cause of
death and varicella was not listed on the death records or was
listed as a contributing cause of death. On the other hand,
misclassiﬁcation could overestimate varicella deaths if dissem-
inated herpes zoster, especially among people who were older
[28, 29] and/or immunocompromised was diagnosed and re-
corded as varicella. We found some evidence of misclassiﬁcation
in the less-pronounced seasonality among deaths in older
adults, which suggests that varicella diagnosis codes in this age
group may have a lower speciﬁcity . Furthermore, it can
be difﬁcult to clinically distinguish varicella from disseminated
herpes zoster. Although there are no published studies on the
validity of the varicella code as the underlying cause of death
on death certiﬁcates, quality assurance of death certiﬁcate data
is maintained by trained nosologists who code conditions at
the state level and, in turn, by nosologists at NCHS who pe-
riodically review data from a sample of the submitted death
certiﬁcates. Furthermore, we compared decedents with varicella
listed as the underlying cause of death with those with varicella
listed as a contributing cause of death and found similar trends
in mortality over time, which suggests that the changes ob-
served are real and not attributable to a change in coding.
Currently, the CDC is collaborating with one large state to
assess the accuracy of the varicella code on death certiﬁcates
by reviewing medical records.
Second, several ICD codes for medical conditions of interest
JID 2000;182 (August) Varicella Deaths in the United States, 1970–1994 389
in this study lack speciﬁcity. For example, Reye’s syndrome is
coded under the ICD-8A in a broad category, “other disease
of the brain,” and there is no speciﬁc code for varicella en-
cephalitis. This limited our ability to monitor varicella deaths
with these 2 CNS complications. Third, information collected
for death records is limited to medical conditions, with no in-
formation on immunosuppressive medical therapies, such as
systemic steroid use. Therefore, this study may underestimate
the number of decedents with preexisting high-risk conditions.
It is too early to evaluate the impact of the varicella vaccine
on mortality. Nevertheless, with the availability of a safe and
effective vaccine, preventing varicella deaths through vaccina-
tion should be a public health priority. Physicians play a key
role by ensuring that their patients are properly vaccinated. A
high proportion of vaccinated people in the population is
needed to achieve herd immunity for the protection of people
who can not be vaccinated and who remain at high risk of
serious disease or death, such as infants and immunocom-
promised people. Coverage levels must increase substantially
above the 1998 national vaccine coverage of 43% among chil-
dren 19–35 months old, to reduce disease burden, including
mortality, among all age groups . Physicians should be
aware that most varicella deaths occur among healthy people,
that adults as well as children die from this disease, and that
varicella deaths continue to occur, despite the availability of an
effective vaccine [5, 6]. Physicians are encouraged to report all
varicella-related deaths to state health departments . In-
vestigating and reporting all varicella-related deaths will pro-
vide more accurate and complete data on people who die from
varicella, such as immunocompromising conditions, therapies,
vaccination status, and childhood residence, which can be used
to improve prevention efforts.
We thank Ken Kochanek, of the National Center for Health Statistics,
Division of Vital Statistics, for technical assistance in interpreting Inter-
national Classiﬁcation of Diseases codes and mortality data, and Barry
Sirotkin, of the National Immunization Program, Division of Data Man-
agement, for compiling the 25-year varicella mortality ﬁle.
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