Download The virtual disappearance of rheumatic fever in the

PERSPECTIVE
The virtual disappearance of rheumatic fever in the
United States: lessons in the rise and fall of disease
T. Duckett Jones Memorial Lecture
LEON GORDIS, M. D., DR. P. H.
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I AM DEEPLY HONORED to have been invited to
give the 1984 T. Duckett Jones Memorial Lecture.
This year marks 40 years since Dr. Jones first published his paper entitled "The Diagnosis of Rheumatic
Fever."' Jones had the foresight to recognize the importance of standardized diagnostic criteria from three
points of view. He wrote: "(1) Otherwise, [without
standardized criteria] the incidence of rheumatic fever
may be interpreted as varying greatly whether the data
are collected by surveys, the development of a rheumatic fever register, making the disease reportable, or
the study of hospital records. (2) The interpretation of
study programs of prevention and care is obviously
dependent on such diagnostic criteria." Jones' third
point dealt with the importance of standardized diagnostic criteria if valid information regarding ultimate
prognosis were to be obtained and provided to patients
and their families. It is noteworthy that the primary
benefits he described were not so much the improved
clinical management of individual patients with rheumatic fever, but rather facilitation of the collection of
meaningful incidence data and evaluation of the effectiveness of prevention programs. In this article I would
like to discuss the dramatically changing incidence of
rheumatic fever and its relation to our preventive efforts. The studies I will present were possible only
because of the broad acceptance and utilization of the
diagnostic criteria promulgated by Dr. Jones 40 years
ago.
Throughout history people have been intrigued by
the apparent appearance and disappearance of human
disease, believed by many to be actions of the gods in
direct response to humain behavior. Over the years
there have been attempts to develop a scientific rationFrom the Department of Epidemiology, Johns Hopkins School of
Hygiene and Public Health, Baltimore.
Supported in part by NHLBI grant T32HL07024.
Address for correspondence: Leon Gordis, M.D., Dr. P.H., Department of Epidemiology, Johns Hopkins School of Hygiene and Public
Health, 615 N. Wolfe St., Baltimore, MD 21205.
This Perspective summarizes Dr. Gordis' presentation as the T.
Duckett Jones Memorial Lecturer at the Annual Meeting of the American Heart Association, Miami Beach, November 1984.
Vol. 72, No. 6, December 1985
ale for explaining these phenomena. I would like to
review the picture of rheumatic fever as it has emerged
in studies we have carried out in Baltimore over a
period of more than two decades. I shall then try to
place the changes that have occurred in the context of
other diseases that have either increased or decreased
in incidence or mortality in the United States during
the 20th century.
The Baltimore studies. The earliest of these studies
were carried out in collaboration with Dr. Milton
Markowitz. In the ensuing years he has continued to be
a stimulus and constructive critic and is, in essence, a
spiritual collaborator in all these investigations. Our
first study in Baltimore examined the incidence patterns of acute rheumatic fever from 1960 to 1964.2 The
findings were marked by dramatic racial differences.
Rates of both initial and recurrent attacks were more
than twice as frequent in blacks as in whites. These
findings were consistent with the observation that the
disease tended to cluster in the predominantly black
areas of the inner city of Baltimore. Relatively few of
the cases occurred in suburban areas.
In a second study we found that from 1960-64 to
1968-70, the rates in blacks in Baltimore dropped dramatically while the rates in whites remained relatively
unchanged. To explain this change we asked the question: Could the decline in incidence in black children
be due to the inner city comprehensive care programs
for children and youth that had been established in the
mid-1960s? A study was therefore carried out to compare the incidence of rheumatic fever in census tracts
eligible for comprehensive care compared to census
tracts not eligible for comprehensive care.' As seen in
figure 1, in the census tracts that were eligible for
comprehensive care, incidence of rheumatic fever
dropped 60% from 1960-64 to 1968-70. In contrast,
there was virtually no change in noneligible census
tracts.
Because many social and economic changes had
taken place during this time, it would be difficult to
ascribe the decline in rheumatic fever specifically to
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0
0
0
0
0
20r
>. BLACKS
'.;
I0-
CLi
WHITES
LLJ
£1J
wX
Hr
1
1960-64
COMPREHENSIVE
CARE
NfET CHANGE - 60.4 %
ALL NON-ELIGIBLE
TRACTS
+2.0%
ALL OF
BALTIMORE
-35.4%
FIGURE 1. Comprehensive care and changes in rheumatic fever incidence, 1960-64 to 1968-70 (Baltimore, black population, ages 5 to 14
years).
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comprehensive care solely on the basis of these findings. A further analysis was therefore carried out with
the following rationale: If the comprehensive care programs were indeed responsible for the observed decline in rheumatic fever by providing quality ambulatory care to children, they could have had such an
impact only in children who had clinically overt pharyngitis. If so, we would expect the decline observed in
rheumatic fever to have been limited to those cases that
had been preceded by clinical pharyngitis and to see
relatively little change in the incidence of cases preceded by subclinical pharyngitis, since such children
would have had no reason to seek medical care and
consequently the comprehensive care programs would
not be expected to have any impact in this group. As
seen in figure 2, when analyzed in this fashion the
entire decline in rheumatic fever was found in cases
that had been preceded by clinically overt acute phar-
25lr
201-
a
1968 -70
1977-81
FIGURE 3. Average annual incidence of first attacks of rheumatic
fever ages 5 to 19, by race. Baltimore, 1960-81.
yngitis. Thus the data up to 1970 were highly consistent with the hypothesis that in Baltimore, the decline
in rheumatic fever, which was limited to blacks, was
primarily a result of the comprehensive care programs
in the inner city.
More recently, we carried out a third study in Baltimore utilizing the same methods as the two previous
investigations. As seen in figure 3, from 1968-70 to
1977-81, incidence rates of rheumatic fever dropped
dramatically in both whites and blacks to extremely
low rates. Perhaps the most dramatic view of these
changes is seen in figure 4, which shows spot maps for
rheumatic fever cases for the first and last 5 year periods of this study, 1960-64 on the left and 1977-81 on
the right. Only five cases were seen in Baltimore from
1977 to 1981, and all were clinically mild.
National data for the United States. These findings are
consistent with data reported from other communities,
such as those of Land and Bisno from Memphis, Tennessee.4 Available evidence suggests that this is also
the pattern in other cities in the United States in most
populations. National data for hospital discharges with
a diagnosis of rheumatic fever from the National Hospital Discharge Survey conducted by the National Center for Health Statistics, and kindly provided by Dr.
Edward Bacon of the Center, confirm this decline (table 1). The decline is also seen when the rates are
Q 15
10
r
...f -
INFECTION
6.3
n-.
7-...0..
PRIOR
k 10)-
1960-64
NO PRIOR
CLINICAL
INFECTION
...
..
6.5
.6
1968-70
FIGURE 2. Changes in the annual incidence of first attacks of rheumatic fever in relation to preceding clinical respiratory infection.
1156
1960 -64
1977*81
7
FIGURE 4. Spot maps for rheumatic fever cases in Baltimore 1960-64
and 1977-81.
CIRCULATION
PERSPECTIVE
TABLE 1
Annual rates (per 100,000) of discharges of patients with rheumatic
fever from short-stay non-federal hospitals in the United States,
1965-83
Year
Discharge
rate
Year
Discharge
rate
1965
1966
1967
1968
1969
1970
1971
1972
14.0
13.3
10.2
8.4
NAA
7.8
8.1
5.6
1973
1974
1975
1976
1977
1978
1979-80
1981-83
5.1
4.8
4.1
3.3
3.5
3.0
2. OB
1.0B
Source: National Hospital Discharge Survey, NCHS.
AData not available.
BAverage annual rate per time period.
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examined by age and race (table 2). Thus we have a
marked decline in rheumatic fever, indeed a virtual
disappearance of the disease in both blacks and whites
in Baltimore, and this appears consistent with most
available data from elsewhere in the United States.
"New" and "disappearing" diseases. What can account
for the extraordinary phenomenon we are observing in
acute rheumatic fever in the United States? To address
this issue I would like to discuss briefly other diseases
that have either appeared or at least increased in incidence or disappeared or declined in incidence in the
course of the 20th century. Among the "new" diseases,
or those that have at least increased markedly in incidence during the last few decades, are: lung cancer,
clear cell carcinoma of the vagina, phocomelia, toxic
shock syndrome, legionnaires disease, Kawasaki disease, Reye syndrome, Lyme arthritis, and AIDS. Each
has attracted considerable interest, including perhaps
most notably the rapid increase in AIDS.
What can account for the relatively rapid appearance
TABLE 2
Annual rates of hospital discharges of patients with rheumatic
fever by age and race, United States, 1965-67, 1972-76, and
1979-83A
Rates per 100,000
Age
0-19 yr
20 yr and older
Race
White
Nonwhite
1965-67
1972-76
1979-83
19.2
8.0
7.0
3.2
2.8
0.8
11.8
17.3
4.4
5.6
1.4
1.4B
AShort-stay non-federal hospitals (source: National Hospital Discharge Survey, NCHS).
BBased on a small sample of records.
Vol. 72, No. 6, December 1985
of a disease? Certainly better diagnosis and recognition
or differences in artifacts of coding can also play a
role. Increased physician awareness of infectious
agents and changes in the prevalence of the agents or in
the biological characteristics of the agents that relate to
virulence may also be critical. For diseases having
other causes, new agents introduced into the environment or new exposures to them may account for the
increase. Finally, removal of certain protective mechanisms may play a role. For example, it has been suggested that Hodgkin's disease has a higher incidence in
upper socioeconomic individuals because such individuals are protected from certain early childhood infections such as Epstein-Barr virus, a model similar to
that seen in polio.5
Below are listed some diseases that seem to have
disappeared or at least declined in incidence during the
20th century:
As a result of planned eradication campaigns:
Infectious diseases
Smallpox
Polio
Nutritional rickets
As a result of changes in medical practice:
Retrolental fibroplasia
Not completely understood:
Stomach cancer
Uterine cancer
Peptic ulcer
Celiac disease
Stroke
Myocardial infarction
Endocardial fibroelastosis
Some of these diseases seem to have declined primarily as a result of planned and well-organized eradication campaigns. These include infectious diseases such
as smallpox and poliomyelitis and diseases such as
nutritional rickets, which have declined in incidence as
a result of specific dietary supplementation. Second,
we have diseases that have almost disappeared as a
result of changes in medical practice. Perhaps the most
dramatic example is retrolental fibroplasia.
Other diseases have disappeared without any specific eradication campaign. For example, stomach cancer
has declined markedly in the United States, as has
uterine cancer, with no explanation immediately at
hand to account for these changes. Other diseases such
as peptic ulcer and celiac disease have also declined
and the causes for the declines remain unknown. Isolated endocardial fibroelastosis, without aortic disease, appears to be much less frequent than in previous
years. Finally, and perhaps most noteworthy are the
1157
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declines in mortality from stroke and coronary heart
disease.
What can account for dramatic decreases in incidence and mortality of disease? Changing diagnostic
approaches and changes in coding can play a role and
produce artifactual changes. For diseases caused by
infectious agents, it is at least theoretically possible
that the virulence of the agent may diminish or the
prevalence of human exposure to the agent may decline. If caused by exposures to other etiologic agents
in the environment, such may change over time as
existing hazards are recognized and controlled. Finally, changes in lifestyle or changes in the quality and
accessibility of medical care may play a role in declines observed in the incidence of disease.
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Possible explanations for the virtual disappearance of
rheumatic fever. With this background, how can we
explain the changes observed in the incidence of rheumatic fever? Reasonably valid population-based incidence data for rheumatic fever did not become available until the 20th century. Hence, although rheumatic
fever has been present for centuries and according to
some, may have been present in antiquity, it is difficult
to state whether at some point in time there was a
sudden appearance of the disease or a sudden rise in the
incidence of the disease. What is clear, however, is
that the 20th century has witnessed a sharp decline in
rheumatic fever, at least in the United States and in
other economically developed countries.
Could the decline in rheumatic fever be due to
changes in the streptococcus itself? Let us examine the
possibilities. The first would be that the incidence of
streptococcal infections has declined. Although some
experts believe that there has, in fact, been a decline in
the incidence of streptococcal infections, it is difficult
to document such a change. In fact, Hall and Breese
have reported from Rochester, New York, that the
number of throat cultures positive for group A streptococci did not decline during a time period when a
decline in rheumatic fever was observed (unpublished
observations). Unfortunately, there is no ongoing systematic data collection system in the United States that
could provide the information needed to address this
issue.
If the incidence of streptococcal infections has in
fact declined, the decline could be part of a cyclical
pattern of increases and decreases in incidence of
streptococcal infections and that we may just be on the
down side of the curve at this point in time. If indeed
there is such a cyclic phenomenon, we might anticipate
another rise in streptococcal incidence in the future and
with it
1158
a possible
rise in rheumatic fever incidence.
Could there have been a change in the prevalence of
rheumatogenic types in our communities or in the incidence of infections produced by rheumatogenic types?
Although there is strong evidence that there are nephritogenic types, the case for rheumatogenic types is not
clear. Support for this contention comes from several
types of evidence: (1) The temporal and geographic
variations observed in rheumatic fever incidence are
consistent with the existence of rheumatogenic and
nonrheumatogenic types. (2) Early data from Kuttner
and Krumweidef suggested differences in rheumatic
fever attack rates depending on the serologic type of
streptococcus in the outbreak. (3) Data from Potter et
al.7 suggest that in Trinidad the serologic types of
streptococci causing rheumatic fever differ from those
causing nephritis even in the same families. (4) Seasonal differences reported in occurrence of rheumatic
fever and of glomerulonephritis are also consistent
with different rheumatogenic potential of different serotypes.8 (5) Rheumatic fever and nephritis rarely occur
simultaneously.
Could there have been a change in the virulence of
the streptococcus over time? This is certainly a possibility, although as McCarty has suggested, given the
fact that no single serologic type has been demonstrated to be rheumatogenic, any changes in virulence
would have had to occur in several serologic types of
streptococci simultaneously.9 Nevertheless, we do see
some evidence consistent with changes in the virulence
of the streptococcus. Scarlet fever has become a much
milder disease over the last few decades and its incidence has perhaps declined. Data from Baltimore suggest that the incidence of poststreptococcal acute glomerulonephritis may also have declined, although not
as markedly as that of rheumatic fever (figure 5). Further evidence consistent with a possible change in virulence of the organism is the changing pattern of antibiotic sensitivity of the streptococcus. High rates of
resistance of streptococci to tetracycline, and to a lesser extent to erythromycin and lincomycin, have been
reported. '0
There is some ambiguity associated with the term
"virulence." Virulence may refer to the capacity of the
streptococcus to adhere to human epithelium, to its
ability to evoke an antibody response, to its ability to
produce clincial pharyngitis or other infection, or to its
rheumatogenic or nephritogenic potential. Streptococcal virulence has been associated with the M protein of
the cell surface, which has antiphagocytic properties
and may also enhance the adherence of the streptococcus to epithelial cells by forming a complex with lipoteichoic acid.11 To date, there is no evidence that the
CIRCULATION
PERSPECTIVE
o
3-
a
2
z
I
2 -
z
C]
inhibit normal antibacterial defenses, and all measures
of macrophage function seem to be affected. 13 Thus the
possibility that viruses may act as a cofactor in promoting the establishment of streptococcal infections or in
some other fashion is not unreasonable. Although
studies in the past of possible associations of viral and
streptococcal infections were not rewarding, the markedly improved technology for viral studies available
only in recent years has not yet been adequately applied to exploring this possibility.
1972
It is also
1974
1976
1
78
FIGURE 5. Incidenice of hospitalized glomerulonephritis, Baltimore
ages 0-19 years, 1972-81
residents,
years,
1972-81.
of stireptococcal strains isolated that are Mtypeable has dec reased and, in fact, data from Rochester suggest that t he percentage of streptococcal isolates
that are M-typ(eable may have increased in recent
years. Data are needed on changes in the adherence
ability of strept ococcal strains isolated over time.
If a change in the virulence of the streptococcus has
indeed taken pla ce, what could have produced it? It has
been suggested that the relatively high proportion of
people in the piopulation who have serum penicillin
levels at any tinne may serve to interrupt the chain of
transmission, wrhich is often also associated with enhanced virulenc :e. If this were the case, one would
expect a decreasse in the percentage of isolated strains
that were M-typ ,eable. It is also possible that nowadays
the streptococci more frequently encounters people
with specific anttibodies that prevent this transmission.
Unfortunately, population-based data on the prevalence rates of a nti-M antibodies are not available.
Another posssibility for explaining the decline in
rheumatic fever is the disappearance of a cofactor that
may operate tog' ether with the streptococcus to produce
rheumatic fever Viruses have been known to affect
host resistance 2and responses to bacterial infections.'2
It is well recoginized that during influenza epidemics
there is an incre,ased risk for both systemic and pulmonary infections caused by many organisms, including
Hemophilus infl luenzae, Staphylococcus aureus, Neisseria Meningitiidis, Escherichia coli, and Streptococcus pneumonia(C. 3 Newborns with upper respiratory
viral infections' were reported long ago by Eichenwald
to be particularl,y susceptible to infections by staphylococci, streptoci occi, and H. influenzae."4 Bacterial
adherence had t been found to be enhanced by experimentally and I naturally acquired viral infections.'5
Antecedent vira il infection potentiates the growth of
several organisn ns in the lung, including group B streptococci.'6 Viral infections have also been shown to
percentage
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,is
Vol. 72, No. 6, December 1985
possible
agent could be
Musherl7 found
that some other environmental
serving as a cofactor. Fainstein and
that smokers had increased
adherence
of pneumococci compared with nonsmokers. Although they did not observe such differences for streptococci, their findings exemplify the possibility that
environmental factors may, in principle, affect bacterial adherence and that such a mechanism could be
operating with the streptococcus, although the possible
agent or agents that may be involved is not known.
To what extent can we attribute the decline in rheumatic fever to medical care and primary prevention
efforts? It seems an inescapable conclusion that at least
part of the observed decline in rheumatic fever must be
due to the prompt and appropriate antistreptococcal
treatment given by physicians throughout the country.
However, although the data in Baltimore for 1968-70
suggest such an explanation, it is difficult to reconcile
the more recent decline in rheumatic fever that has
occurred in both blacks and whites in Baltimore, with
changes in medical care and in the way health services
are delivered. In assessing any decline in disease incidence, however, there are potential hazards in assuming that the changes observed are in fact due to medical
advances and to the care provided. Rene Dubos wrote,
"When the tide is receding from the beach, it is easy to
have the illusion that one can empty the ocean by
removing water with a pail."'8 Some years ago, Dr.
Edward Kass pointed out that major scientific advances that have enhanced our medical care for diseases such as tuberculosis have not been clearly related
to the major declines in incidence and mortality of such
diseases'9 (figure 6). When we examine a similar presentation of the data for rheumatic fever as shown in
figure 7, we see that the decline in rheumatic fever
mortality clearly began before antistreptococcal agents
became available.
Could the decline in rheumatic fever be due to some
change or changes in the host? Given the relatively
short period of time during which the incidence of the
disease has declined, the changes cannot be accounted
for by genetic alterations in human populations. It is
1159
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._
0
cg
E
0
0
:5
0
4D
ax
c
1860 1870 1880 1890 1900 1910 1920 1930 1940 1950
1860 1870 1880 1890 1900 1910 1920 1930 1940 1950
Meon annual deoth rote from whooping cough in
children under 15 yeors of age, Englond ond Wales.
Koss 1971.
Mean annual deoth rote from diptheria in children
under 15 years of age, Englond and Woles. Koss 1971.
ZOUU0r
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c~
2000
b._
ISOO
-5
1000
2at
c)
streptococcus
identified
penicillin
500
sulfonamides
.~~~~~~~~
1860 1870 1880 1890 1900 1910 1920 1930 1940
1950
Mean annuol death rate from scorlet fever in children
under 15 years of age, England and Woles. Kass 1971.
Mean annual deoth rate from respirotory tuberculosis,
Englond and Wales. Koss 1971
FIGURE 6. Decline in death rates of diphtheria, whooping cough, Scarlet fever, and respiratory tuberculosis in England and
Wales. (Reprinted, with permission, from Kass. 19)
conceivable, however, that improved life-style factors
such as nutrition may have affected the host and made
him more resistant to streptococcal infections.
It is important to note that host factors have long
been recognized as playing a role in the risk of rheumatic fever. The higher risk of rheumatic fever in
children has generally been attributed to their greater
exposure to streptococcal infections. However, it has
been reported that streptococci adhere more vigorously
to cells from young compared with middle-aged subjects. 17 This suggests the possibility that endocrine factors, for example, may affect infectivity and rheumatogenicity. Examples from other diseases support the
notion that such host factors above and beyond any
genetically determined susceptibility may play a role.
For example, it is well recognized that pregnancy
places a woman at increased risk of acquiring poliomyelitis. Particularly in the prevaccine era, it was also
recognized that tonsillectomy increased the risk for
bulbar poliomyelitis.
It is interesting to reflect on the reasons we have so
much difficulty today in explaining the marked decline
in the incidence of rheumatic fever. One aspect of this
problem specifically merits discussion because it may
have implications for our approaches to the etiologies
of other diseases in the future. After Lancefield pub1160
lished her landmark work on the streptococcus, investigators interested in rheumatic fever quite appropriately focused their attention on confirming the
relationship between the streptococcus and rheumatic
fever and on elucidating the pathogenetic pathways
involved. As the streptococcus was pursued, the possible etiologic role of factors other than the streptococcus in rheumatic fever received relatively little attention. That such factors genetic, environmental, or a
combination thereof
are in fact probably playing
C
0
O.
10
8
0
O
6
Classification
of strep
0
~~~~~sulfonamides
4
penijili
0
c)
CD
1910
1920
1930
1940
1950
1960
1970
1977
Years
FIGURE 7. Crude death rates from rheumatic fever, United States,
1910-1977.
CIRCULATION
PERSPECTIVE
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such a role is suggested by the data from the studies
that yielded estimated rheumatic fever attack rates of
3% in the military and of 0.3% in civilian populations
of children. Thus 97 of every 100 recruits who acquired a streptococcal infection did not develop rheumatic fever and 997 of every 1000 children who acquired streptococcal infections did not develop
rheumatic fever. Why not? What factors could account
for the small percentage of individuals with streptococcal sore throats who subsequently developed rheumatic fever, even in days when rheumatic fever was more
common in the United States?
In this context, it is worthwhile to look at the approaches taken by epidemiologists to study the etiology of chronic diseases today, particularly when it is
desired to explore the possible role of a number of
etiologic agents. The approach often used initially is
the case-control study (figure 8). In this design, patients with the disease ("cases") are compared with
control subjects without the disease and the proportions of cases and controls with specific characteristics
or exposures are compared. In the case of rheumatic
fever, in which the streptococcus had been clearly implicated, case-control studies addressing genetic and
environmental factors other than the streptococcus
would have been very valuable. Thus a study of viral
factors in rheumatic fever in association with streptococcal infections could be carried out by comparing
cases of rheumatic fever with appropriately selected
controls and determining what proportion of cases and
of controls had specific prior viral infections of interest. Because the case-control design permits the investigation of a number of possible etiologic factors at the
same time, it would be possible to develop a predictive
model of which patients with streptococcal infections
are at high risk for rheumatic fever. Until now, prediction of development of rheumatic fever has primarily
been addressed by focusing on the characteristics of
the streptococcus. Although this is a reasonable approach, it should not exclude consideration of host and
other environmental characteristics. In his 1982 T.
Duckett Jones Lecture, Dr. Elia Ayoub addressed host
genetic factors in the genesis of rheumatic fever.20 I
ED
EXPOSED
DISEASE1
|DISEASE
|
"CASES"
EXPOSED
NO
DISEASE
"CONTROLS"
FIGURE 8. Schematic design of a case-control study.
Vol. 72, No. 6, December 1985
would suggest that other host and environmental characteristics should also be considered.
The relative lack of rigorously designed and conducted case-control studies in the search for a full
understanding of the etiology of rheumatic fever is
understandable, since much of Lancefield's work was
published at a time when the case-control design had
not yet received full recognition and acceptability and
was ony sporadically used. Not until the 1950s, when
the case-control study design played a major role in
establishing the relationship between cigarette smoking and lung cancer, was the case-control study fully
legitimized. By this time the streptococcus was viewed
as the full solution to the etiology of rheumatic fever,
and as a result, a diligent search for other variables that
might be involved was never carried out. Thus rheumatic fever began its dramatic decline in the United
States before adequate attempts had been made to investigate the role of other etiologic agents above and
beyond the streptococcus. Consequently, in the absence of a full understanding of the etiology of rheumatic fever today, we are unable to definitively explain
its decline.
Rheumatic fever in the third world. Although the risk of
rheumatic fever has been sharply declining in the United States, the picture is far different in developing
countries. Worldwide, rheumatic heart disease remains the most common form of acquired heart disease
in children and young adults and an important cause of
all heart disease seen in adults. The status of rheumatic
fever and rheumatic heart disease in developing countries has been succinctly summarized by Markowitz2l:
(1) Rheumatic fever is the most frequent cause of heart
disease in the 5 to 30 year age group. (2) Acute rheumatic fever and rheumatic heart disease are two of the
most common causes of death in young people. (3)
Rheumatic heart disease causes 25% to 40% of all
cardiovascular disease. Estimated prevalence of rheumatic heart disease in India schoolchildren is six to 11
per 1000.22 Thirty-three to fifty percent of all hospital
admissions for heart disease are for rheumatic heart
disease.
Even in the United States, however, there are areas
and population groups that have not clearly shared in
the decline in incidence of rheumatic fever. For example, in the Navajo from 1962 to 1977, the annual attack
rate was 12.4 per 100,000 for all ages, with the highest
rate of 23.4 per 100,000 in the 10 to 14 year age
23
group. Rates of 96.5 per 100,000 have been reported
in Samoans living in Hawaii, with 50% of the patients
having carditis.24 Recently, the Colorado Department
of Health reported 14 confirmed cases of rheumatic
l1161
GORDIS
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fever in the first 6 months of 1984 compared with only
two to three cases reported annually in recent years.25
Two points emerge: First, any hypothesis developed to
explain the decline observed in rheumatic fever in most
of the United States must also explain its persistence in
certain American population subgroups and in the developing world. Second, this persistence both in the
United States and abroad should preclude any complacency on our part in regard to rheumatic fever.
Conclusion. In conclusion, although the group A
streptococcus is the critical etiologic agent of rheumatic fever, the disease may well be multifactorial in
origin. While improved medical care and the use of
penicillin and other antibiotics have contributed significantly to the decline of rheumatic fever in the United States, the decline antedated the availability of antibiotics, and in addition the changes in rheumatic fever
in the United States cannot be fully accounted for solely by medical care and antibiotic use. The difficulty is
that we lack adequate information regarding other possible cofactors. Studies of such factors are not feasible
in the United States today in view of the very low
incidence of the disease, but such etiologic investigations could be initiated and conducted in developing
countries.
From the clinical standpoint, the low risk of rheumatic fever today suggests that perhaps we should
reassess present policies regarding our hunt for the
streptococcus and our determination to eradicate it.
However, any relaxation of our currently recommended approaches to streptococcal infections should be
undertaken with great caution, since we do not understand the reasons for the decline and consequently cannot fully anticipate the possible results of any relaxation in policy. In any case, such a relaxation would be
highly inappropriate for developing countries in which
the risks of rheumatic fever and rheumatic heart disease remain so high.
Finally, there is an urgent need for additional research both on the biology of the streptococcus and the
pathogenetic mechanisms involved in the development
of rheumatic fever as well as on other factors that may
interact with the streptococcus and influence the risk of
disease. Such research may not only be valuable in
improving the health of populations that are at high
risk for rheumatic fever in developing countries, but
may also shed light on the pathogenesis of other nonsuppurative sequelae of infectious diseases.
1162
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CIRCULATION
The virtual disappearance of rheumatic fever in the United States: lessons in the rise and
fall of disease. T. Duckett Jones memorial lecture.
L Gordis
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Circulation. 1985;72:1155-1162
doi: 10.1161/01.CIR.72.6.1155
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