Context Recent increases in infectious disease mortality and
concern about emerging infections warrant an examination of longer-term
trends.
Objective To describe trends in infectious disease mortality in
the United States during the 20th century.
Design and Setting Descriptive study of infectious disease
mortality in the United States. Deaths due to infectious diseases from
1900 to 1996 were tallied by using mortality tables. Trends in
age-specific infectious disease mortality were examined by using
age-specific death rates for 9 common infectious causes of death.
Subjects Persons who died in the United States between 1900 and
1996.
Main Outcome Measures Crude and age-adjusted mortality rates.
Results Infectious disease mortality declined during the first 8
decades of the 20th century from 797 deaths per 100,000 in 1900
to 36 deaths per 100,000 in 1980. From 1981 to 1995, the
mortality rate increased to a peak of 63 deaths per 100,000 in
1995 and declined to 59 deaths per 100,000 in 1996. The decline
was interrupted by a sharp spike in mortality caused by the 1918
influenza epidemic. From 1938 to 1952, the decline was particularly
rapid, with mortality decreasing 8.2% per year. Pneumonia and
influenza were responsible for the largest number of infectious disease
deaths throughout the century. Tuberculosis caused almost as many
deaths as pneumonia and influenza early in the century, but
tuberculosis mortality dropped off sharply after 1945. Infectious
disease mortality increased in the 1980s and early 1990s in persons
aged 25 years and older and was mainly due to the emergence of the
acquired immunodeficiency syndrome (AIDS) in 25- to 64-year-olds and,
to a lesser degree, to increases in pneumonia and influenza deaths
among persons aged 65 years and older. There was considerable
year-to-year variability in infectious disease mortality, especially
for the youngest and oldest age groups.
Conclusions Although most of the 20th century has been marked by
declining infectious disease mortality, substantial year-to-year
variation as well as recent increases emphasize the dynamic nature
of infectious diseases and the need for preparedness to address
them.
Over the last 100 years, North America and Europe have
experienced a substantial decline in mortality and an increase in life
expectancy. The "theory of epidemiologic transition" attributes
these trends to the transition from an "age of pestilence and
famine," in which the mortality pattern was dominated by high rates
of infectious disease deaths, especially in the young, to the current
"age of degenerative and man-made diseases" in which mortality from
chronic diseases predominates.1,2 According to estimates
from the Global Burden of Disease Study, infectious diseases now
account for only 4.2% of all disability-adjusted life years lost
(DALYs, a measure of the burden of diseases and injuries) in countries
like the United States with established market economies, whereas
chronic and neoplastic diseases account for 81.0%.3
Until recently, it was assumed that the epidemiologic transition
had brought about a permanent reduction in infectious disease mortality
in the United States. However, the emergence or reemergence in the
1980s of such diseases as the acquired immunodeficiency syndrome (AIDS)
and tuberculosis demonstrated that gains against infectious diseases
cannot be taken for granted.4,5 An outbreak of avian
influenza in Hong Kong in late 1997 by a strain (H5N1) not previously
known to infect humans6 is a reminder that pandemic
influenza continues to pose a threat.
In the United States, mortality due to infectious diseases increased
58% from 1980 to 1992,7 a trend that was unforeseen. To
determine when this trend began and to characterize longer-term trends
in the United States, we examined US mortality records since 1900, when
the federal government first began to track mortality data annually.
Sources of Mortality Data
Data were obtained from yearly tabulations of causes of death on file
at the Division of Vital Statistics of the Centers for Disease Control
and Prevention's National Center for Health Statistics and from public
use mortality data tapes from 1962 through 1996.
The US federal government began publishing mortality statistics
on an annual basis in 1900 after establishment of the
death-registration system.8 Initially,
data were gathered only from the "death-registration area," which
included 10 states, the District of Columbia (collectively known as the
"death-registration states"), and 153 cities outside these states.
The system was gradually expanded to include all states by 1933. All
registered deaths were entered into the system for every year except
1972, when a sample of half of all deaths was entered. Deaths occurring
in military personnel outside the United States were not
included.8
The cause or causes of death obtained from death certificates
were coded according to the particular revision of the
International Classification of Diseases (ICD) that
was in use at the time (successive revisions were implemented starting
in 1900 [ICD-1], 1910 [ICD-2], 1921
[ICD-3], 1930 [ICD-4], 1939 [ICD-5],
1949 [ICD-6], 1958 [ICD-7], 1968
[ICD-8], and 1979 [ICD-9]). The underlying
cause of death was selected from the array of medical conditions listed
on the death certificate according to standardized
algorithms.8 For this study, only the
underlying cause of
death was considered when multiple causes of death were listed.
Population data used in the calculation of mortality rates were also
obtained from the National Center for Health Statistics. The data for
years prior to 1933 included only the population of the
death-registration states or death-registration area, corresponding to
the scope of the mortality data being used.
Overall Infectious Disease Mortality
From 1900 through 1948, tables for the death-registration area showing
mortality by each cause were analyzed. From 1949 through 1996, tables
with mortality broken down by 252 to 282 causes were examined. Deaths
due to diseases or categories of diseases that are always or almost
always infectious were summed for each year to give the total number of
infectious disease deaths. These diseases (using the original
terminology) were typhoid fever, typhus fever, relapsing fever,
malaria, smallpox, measles, scarlet fever, pertussis, diphtheria,
croup, influenza, miliary fever, asiatic cholera, cholera nostras,
dysentery, plague, yellow fever, leprosy, erysipelas, purulent
infection, septicemia, glanders, anthrax, rabies, tetanus, mycoses,
tuberculosis, rickets, syphilis, gonococcus infection, other
"epidemic, endemic, or infectious diseases," acute articular
rheumatism (1900 through 1920), acute rheumatic fever (1921 and
later), encephalitis, meningitis, acute poliomyelitis, otitis media,
mastoiditis, acute endocarditis, chronic or unspecified endocarditis
(1930 to 1940, 1949 and later), "chronic affections of the [heart]
valves and endocardium" (1941 to 1948), acute bronchitis,
bronchopneumonia, pneumonia, pleurisy, lung abscess, gangrene of the
lung, diarrhea, enteritis, ankylostomiasis, intestinal parasites,
appendicitis, infections of the kidney, typhlitis, hydatid tumor of the
liver, abortion with septic conditions, ectopic gestation with septic
conditions, puerperal septicemia, infections of the newborn, gangrene
of the skin, furuncle, acute abscess, osteomyelitis, cellular immune
deficiency (1980 through 1986), and AIDS (1987 and later).
Nine categories of infectious disease were analyzed as separate
categories: pneumonia and influenza (analyzed as a single category),
tuberculosis, diphtheria, pertussis, measles, typhoid fever, dysentery,
syphilis ("syphilis and its sequelae"), and AIDS. These categories
were also analyzed as a 9-cause aggregate. The first 8 were chosen
because they were the most common infectious causes of death in the
first half of the century.9,10 Tabulations, by age, of
mortality rates in the death-registration states were available for
each of these diseases for the entire study period One additional cause
of death, acute poliomyelitis, was also examined. Since data were not
available for all years and age-specific rate tables have not been
compiled, poliomyelitis mortality was not included in the 9-cause
aggregate.
Data on AIDS deaths were obtained from public use data files from 1980
to 1996 by counting all deaths in which the underlying cause was coded
as 042.0 to 044.9 (AIDS-related codes, first used in 1987) or 279.1
("cellular immune deficiency," the code under which AIDS was placed
prior to 1987).7,11
Age Categories and Age Adjustments
To examine age-specific trends, we analyzed the 9-cause
aggregate, which included the majority of infectious disease deaths.
The 11 age categories from the original tabulations were merged to form
5 mutually exclusive age groups (0-4 years, 5-24 years, 25-44 years,
45-64 years, and ≥65 years). Where indicated, mortality rates were
age-adjusted to the projected year 2000 population by the direct
method12 using the original 11 age categories.
To adjust for revisions in the ICD, comparability ratios were
applied to the data.9,13 These comparability ratios were
determined by coding deaths at the years of ICD changes using
both the old and the new classification and then comparing the results.
Comparability ratios were not available to adjust for the changes
between ICD-1 through ICD-4. All comparability ratios
since the change to ICD-4 were available for pneumonia and
influenza, tuberculosis, and syphilis. No ratios were needed for AIDS,
which was not diagnosed before the implementation of ICD-9.
For the other 5 disease categories, 17 of the 25 comparability ratios
were available for the changes that took place after ICD-4.
Linear regression was used to estimate the magnitude of trends in
mortality rates. In each case, the model included the logarithm of the
mortality rate as the dependent variable and the year as the
independent variable. Mortality rates from 1918 through 1922 were
removed from the data so that trends could be calculated without being
influenced by the 1918 influenza pandemic.
Infectious disease mortality in the United States during the
20th century has been characterized by 4 trends as well as a
pronounced spike attributable to the 1918
influenza pandemic (Figure 1). From 1900 to
1937, the crude infectious disease mortality rate decreased by
approximately 2.8% per year from 797 deaths per 100,000 persons
in 1900 to 283 in 1937. This was followed by a 15-year period during
which the rate fell by 8.2% per year to 75 deaths per 100,000
in 1952. The decline then slowed again to 2.3% per year until 1980 (36
deaths per 100,000) after which mortality increased by 4.8% per
year to 63 deaths per 100,000 in 1995. In 1996, infectious
disease deaths decreased for the first time since 1982, falling to a
rate of 59 deaths per 100,000.
The decline in infectious disease mortality paralleled the drop in
all-cause mortality during the first half of the 20th century
(Figure 2). The crude mortality rate
from noninfectious causes remained relatively constant during this
period, although there was some year-to-year fluctuation. Increases
generally occurred in the same years that increases were registered in
the infectious disease mortality rate.
Trends in the 9-cause aggregate of infectious disease mortality
were similar to trends in overall infectious disease mortality for the
4 time periods (rates of change: −2.7%, −7.8%, −2.3%, and +6.1%
per year for earliest to latest time periods). The shape of this curve
changed little when the data were age-adjusted to the projected year
2000 population (rates of change: −2.1%, −8.0%, −2.4%,
and +4.6% per year), although the decrease in the first segment and increase in
the last segment were less prominent. Adjustment of the data to account
for changes in disease classification also resulted in little change in
the general shape of the curve (rates of change: −2.8%, −7.0%,
−1.8%, and +6.1% per year).
The 9-cause aggregate used to examine age-specific trends included 62%
to 78% of all infectious disease deaths in all years except 1918, when
it included 87%. There was no significant trend in this ratio over the
course of the study (P>.05).
Trends in the 9-cause aggregate varied by age group (Figure 3). The decline in the mortality rate in
the first 8 decades of the century was seen in all age groups. The
increase after 1981 was seen only in persons aged 25 years and older.
In the 25- to 44-year-olds and 45- to 64-year-olds, the increase after
1981 was primarily due to deaths from AIDS, while in the oldest age
group (≥65 years), the increase was primarily due to
increased deaths from pneumonia and influenza.
During the first decade of the century, the 9-cause aggregate caused a
substantial proportion of all deaths in 5- to 24-year-olds (average:
48% of all deaths) and 25- to 44-year-olds (43%). Tuberculosis alone
accounted for more than 25% of deaths in both age groups. By the
1970s, infectious diseases caused only 3% of deaths in these age
groups.
The 1918 spike in mortality was very pronounced in the 5- to
24-year-olds and the 25- to 44-year-olds (respective peaks: 3.6 and 4.0
times the rates predicted by regression). The mortality rate in that
year was of even greater magnitude in the youngest age group, although
the spike was not as large relative to the rates immediately before and
after. The spike was less prominent in the 45- to 64-year-olds and was
hardly discernible in the oldest age group. Much smaller increases in
infectious disease mortality occurred in the youngest age groups during
the influenza pandemics of 1957 (the "Asian flu") and 1968 (the
"Hong Kong flu").
The year-to-year fluctuation in mortality also varied by age group.
This fluctuation was most pronounced in the youngest and oldest age
groups, reflecting the large contribution of influenza and pneumonia to
mortality in these age groups.
Trends by Disease Category
The proportion of all infectious disease deaths caused by
influenza, pneumonia, and tuberculosis averaged 60.1%
(Figure 4, A). Influenza and pneumonia constituted
the largest single disease category, averaging 44.4% of all infectious
disease deaths (range: 23.4% in 1906 to 67.2% in 1980). Mortality
from tuberculosis was similar to that of pneumonia and influenza during
the first half of the century but fell more rapidly than the latter
after 1950. Mortality from pneumonia and influenza was highly variable
from year to year, while mortality from tuberculosis showed little such
variability.
Deaths due to typhoid fever and, to a lesser degree, dysentery, dropped
markedly during the first half of the century; by 1950, mortality from
these 2 diseases was less than 1 death per 100,000 persons per
year (Figure 4, B). Deaths due to diphtheria, pertussis, and measles
showed similar trends: there were large decreases during the first half
of the century to low levels by 1950 (Figure 4, C). In contrast, polio
mortality fell only marginally during the first 4 decades and then
increased until the first polio vaccine was licensed in 1955. Polio
mortality showed much year-to-year variability as well as a spike in
1916, corresponding to a major epidemic that started in New York City
and swept through the northeastern United States during the summer of
that year.14
Syphilis mortality increased early in the century and remained
relatively level until 1940 (Figure 4, D). Between 1940 and 1950,
syphilis mortality dropped sharply and was less than 0.2 per
100,000 per year by 1975. AIDS mortality increased throughout
the 1980s and early 1990s. By the mid 1990s, the mortality rate was
comparable to that of syphilis earlier in the century. From 1995 to
1996, the AIDS mortality decreased for the first time, falling from
16.4 to 11.8 per 100,000.
During the first 8 decades of the 20th century, the infectious disease
mortality rate in the United States declined substantially, consistent
with the concept of epidemiologic transition. Improvements in living
conditions, sanitation, and medical care probably accounted for this
trend. But over a 15-year period starting in 1981, this trend reversed,
with infectious disease deaths consistently increasing from year to
year for the first time since the federal government began tracking
mortality statistics. Now, as the end of the century nears, infectious
disease deaths may again be declining; a 7% drop
was registered in 1996, largely because of a substantial decline in
AIDS mortality.15,16
A closer examination of the decline from 1900 to 1980 revealed that it
was characterized by 3 distinct periods. During the first (1900 to
1937) and third (1953 to 1980) periods, infectious disease mortality
fell by 2.3% to 2.8% per year. During the 15 years between these
periods, the annual decline in the infectious disease mortality rate
accelerated to 8.2%. The disease categories that contributed most to
this decline were pneumonia and influenza, which fell sharply from 1938
to 1950 and subsequently leveled off for several years, and
tuberculosis, which fell abruptly from 1945 to 1954 and continued to
fall until the mid 1980s. These declines coincided with the first
clinical use of sulfonamides (1935), antibiotics (penicillin in 1941
and streptomycin in 1943), and antimycobacterials (streptomycin, first
used against tuberculosis in 1944, para-aminosalicylic acid in 1944,
and isoniazid in 1952).17
However, the reasons for the
steep decline from 1938 to 1952 are probably many and cannot be
determined by examination of the mortality data alone.
The use of mortality data to evaluate disease burden has limitations.
For one, the mortality rate is an incomplete indicator of disease
burden in that it does not account for varying numbers of potential
years of life lost at different ages or for productive years lost
because of disability. Indicators such as the DALY, used as the
principal metric in the Global Burden of Disease project, would provide
a different perspective on the overall burden of disease.3
Such indicators have limitations as well, most notably that they depend
on the particular system used to
weight deaths and disability.18,19
Furthermore, mortality statistics are only as accurate as the data
provided by physicians who fill out death certificates. Validation
studies have shown that the major ICD disease category (ie,
categories such as infectious diseases, respiratory diseases, or
cardiovascular diseases) listed as the underlying cause of death on
death certificates differs from that determined by autopsy in 12% to
29% of cases.20-23 This may lead
infectious diseases to be
imprecisely represented in mortality data.24,25 In
addition, changes over time in autopsy rates and in diagnostic
capabilities may affect trends in mortality statistics. Despite these
deficiencies, no other surveillance data can match the completeness and
longevity of mortality data.
The decrease in mortality before 1980 and the increase after 1981 are
not likely to be due to changes in the age structure of the US
population alone. These trends remain when the data are age-adjusted
and adjusted for changes in ICD coding. The latter adjustment
should be considered an approximation, since each of the comparability
factors used in this adjustment had been derived from mortality data
from a single year and may not be applicable to other years.
The volatile nature of infectious diseases is apparent in
Figure 1. The sawtooth appearance of the first half of the curve
reflects the periodic spikes in incidence that characterize the
epidemiology of diseases such as measles (every 2-5
years),26 pertussis (every 2-5 years),27
diphtheria (approximately every 10 years),28 and
especially influenza (every 2-3 years).29 Infectious
diseases of a more chronic nature, such as tuberculosis or AIDS, show
much less year-to-year variability.
The jump in mortality during the 1918 influenza pandemic, in which 20
to 25 million persons worldwide died from "Spanish flu," is the
most visible manifestation of the potential volatility of infectious
diseases. The spike in mortality was most prominent in 5- to
44-year-olds, reflecting the disproportionate mortality suffered by
young adults during that pandemic.30 Although influenza
pandemics since 1918 have not caused mortality on the same scale, it is
conceivable that a future pandemic with a particularly virulent strain
could cause another large spike in the infectious disease mortality
curve.
Even as the 20th century closes with much reduced death rates
from infectious diseases, numerous episodes as well as recent trends
remind us how dynamic the factors are that influence the emergence and
reemergence of infectious diseases.4 Infectious disease
mortality did not continue to decline as one might have predicted had
Figure 1 been constructed in 1980. And since there is no guarantee that
future trends will be stable, it remains important to be vigilant over
the threats posed by microbes.31
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