Extrapulmonary Tuberculosis in the United States1- 3
HANS L. RIEDER, DIXIE E. SNIDER, JR., and GEORGE M. CAUTHEN
Introduction
From 1963 to 1986, the number of reported cases of pulmonary tuberculosis in the United States declined from 49,203 to 18,977, an average annual decline of 1070. In contrast, over the same period 01 time, the number of reported extrapulmonary tuberculosis cases declined only 0.9070 annually (figure 1). The failure of extrapulmonary tuberculosis to decline at the same rate as pulmonary tuberculosis has been noted before (1). Possible explanations have included: (1) increased recognition/reporting, (2) overdiagnosis, (3) actual failure to decline, and (4) a combination of these factors (2). It was the purpose of this analysis to describe the demographic characteristics of patients with extrapulmonary tuberculosis in the United States and to compare them with the characteristics of patients with pulmonary tuberculosis. The data from this study suggest one hypothesis to explain the relatively small decline in extrapulmonary tuberculosis over time and several hypotheses to explain the differences in site of disease in various demographically defined groups. Methods In 1986,22,764patients with tuberculosis with known major site of disease were reported to the Centers for Disease Control, of which 3,991 (17.5070) had an extrapulmonary site reported as the major site. After exclusion of 262 patients with incomplete information, 22,506 (98.9070) with known age, race/ethnicity, sex, and country of birth were available for analysis. Patients were divided by major site of disease into pulmonary and eight extrapulmonary categories: lymphatic, pleural, genitourinary, bone and joint, miliary, meningeal, and all other forms combined. Patients were also stratified by age, race/ethnicity, sex, and country of origin (table 1). For each of these demographic characteristics, the stratum with the most cases of pulmonary tuberculosis was arbitrarily chosen as the reference stratum for comparing disease site distributions in terms of relative odds. For example, among female patients, 6,119sites were pulmonary, and 174 were bone and joint as the major site of disease; among male patients, 12,445 siteswerepulmonary and 211 werebone and joint. Thus, the observed odds of bone
SUMMARY From 1963 to 1986, the number of reported cases of pulmonary tuberculosis in the United States declined an average of 5.0% annually, and the number of cases of extrapulmonary tuberculosis declined an average of 0.9% annually over the same period. In 1986, 17.5%of all cases of tuberculosis wereextrapulmonary. Of pUlmonarycases, 63.0% occurred among racial ethnic minorities and the foreign-born, whereas of extrapulmonary cases, the respective proportion was 71.2%. After adjustment for other variables, the proportion of extrapulmonary tuberculosis among all patients with tuberculosis by age was found to be largest In children and generally to decrease with increasing age, larger among black, Asian, and American Indian than among non-Hispanic white patients, larger among female than among male patients, and larger among the foreign-born than among patients born in the United States. The smaller decline in extrapulmonary tuberculosis over the years may be partially due to changes in the demographic characteristics of patients with tuberculosis. Considerable differences in susceptibility to different sites of extrapulmonary tuberculosis by age, race/ethnlcity, sex, and country of origin were found. The reasons for these differences remain AM REV RESPIR DIS 1990; 141:347-351 largely unexplained.
and joint to pulmonary cases was 174/6,119 among female and 211/12,455 among male patients. Using male patients as the reference category, the observed relative odds werethus (174/6,119)/(211/12,445) = 1.68 among female patients relative to male patients, and (211/12,445)/(211/12,445) = 1 among male patients relative to male patients by definition. This can be interpreted as showing that female patients with tuberculosis are 1.68 times more likelyto havebone and joint tuberculosis than are male patients. To isolate the effect of the variable of interest, the observed relativeodds wereadjusted (adjusted relative odds = ARO) to control for the effects of other variables. For example, foreign-born patients with tuberculosis do not have the same age, race/ethnicity, and sex characteristics as do U.S.-born patients; therefore, adjustment for differences in age, race/ethnicity, and sex is necessary to artificially make U.S.-born and foreign-born patients comparable with regard to age, race/ ethnicity, and sex in order to isolate the effect of being foreign-born. Adjusted relative odds were estimated by the maximal likelihood method in a log-linear categorical model of the proportions with disease at each site (3,4). Significance tests and 95070 confidence intervals were also derived from the model. Pulmonary versus all extrapulmonary disease sites combined was similarly modeled using a computer program written by James A. Tonasica, Ph.D. (Johns Hopkins School of Hygiene and Public Health, Baltimore, MD). From this model, adjusted proportions with extrapulmonary disease in various age, race!ethnicity, sex,and country of birth groups could be estimated.
Results
Of the 3,942 extrapulmonary tuberculosis cases (17.5070 of the total 22,506 cases analyzed in the model), 1,219 (30.9070) were lymphatic, 905 (23.0070) werepleural, 469 (11.9070) were genitourinary, 385 (9.8070) were bone and joint, 289 (7.3070) were miliary, 183(4.6070) were meningeal, 132 (3.3070) were peritoneal, and 360 (9.8070) were all other forms combined. Sixty-three percent of pulmonary and 71.2070 of extrapulmonary cases occurred among racial/ethnic minorities and the foreign-born, whereas 37.0070 of pulmonary and 29.8070 of extrapulmonary cases occurred among non-Hispanic whites born in the United States. The proportion of bacteriologically confirmed extrapulmonary cases was 77070.
All Extrapulmonary Forms Combined The age group with the largest propor-
(Received in original form March 6, 1989 and in revised form July 5, 1989) I From the Division of Tuberculosis Control, Centers for Disease Control, Atlanta, Georgia. 2 Presented in part at the Annual Meeting of the American Thoracic Society, Las Vegas, Nevada, May 8-11, 1988. 3 Requests for reprints should be addressed to Technical Information Services, Center for Prevention Services, Mailstop E-06, Centers for Disease Control, 1600 Clifton Road, N.E., Atlanta, GA 30333.
347
348
RIEDER, SNIDER, AND CAUTHEN
Cases
United States, to have extrapulmonary tu berculosis.
(log scale)
::J·· · · ·
~~~m.~n~ry•..•..•..•..•..•
10000
Extrapuimonarv ~
"'
~....
~
.
.
'"
-.
3000
1000 iii
63
66
Ii'
67
i
t
69
ii,
71
73
iii
76
iii
77
79
I
81
iii
83
I
i
I
86
Year
Fig. 1. Reported number of cases of pulmonary and extrapulmonary tuberculosis in the Unites States from 1963 to 1986 (asterisks). The best fitting curves (dotted lines) were obtained by linear regression of the year of report on the logarithm of the number of cases for each year, shown separately for the years before and after the change in reporting criteria in 1975, from which time relapses were to be counted again if the time interval between relapse and previous episode exceeded 12 months.
tion of extrapulmonary tuberculosis cases was children younger than 15 yr of age (table I). By race/ethnicity, American Indians/ Alaskan Natives were most likely to have extrapulmonary tuberculosis; blacks and Asians/Pacific Islanders were more likely than non-Hispanic whites to have extrapulmonary tuberculosis. Female patients were more likely than male patients, and foreign-born patients were more likely than patients born in the
Extrapulmonary Tuberculosis by Site Lymphatic (figure 2a). Patients younger than 15yr of age were the age group most likely (ARO, 7.5) to have lymphatic tuberculosis. Patients younger than 65 yr of age in all age groups were relatively more likely to have lymphatic tuberculosis than patients in the 65 yr and older reference group, but there was no regular pattern by age. Black (ARO, 1.3) and Asian/Pacific Islander patients (ARO, 1.6) were more likely to have lymphatic tuberculosis than were non-Hispanic white patients. Female patients (ARO, 2.2) were more likely to have lymphatic tuberculosis than were male patients. Foreignborn patients were more likely (ARO, 1.7) to have lymphatic tuberculosis than were patients born in the United States. Pleural (figure 2b). Patients younger than 15 yr of age were least likely (ARO, 0.4), and patients-IS to 24 and 34 to 44 yr of age were most likely to have pleural tuberculosis. American Indian/Alaskan Native patients were most likely among all racial/ethnic groups (ARO, 1.8)to have pleural tuberculosis. No significant differences were found between male and female patients, and between patients born in the United States and the foreign-born. Genitourinary (figure 2c). Cases of
genitourinary tuberculosis were least likely to occur in children (ARO, 0.1), and increasingly more likely to occur with increasing age. Cases among blacks (ARO, 0.3) and Asians/Pacific Islanders (ARO, 0.6) were less likely to be genitourinary than cases among non-Hispanic whites, but cases among American Indians/ Alaskan Natives were more likely to be genitourinary (ARO, 2.0). Female (ARO, 1.8)and foreign-born patients (ARO, 1.9) were more likely to have genitourinary tuberculosis than were male and U.S.born patients, respectively. Bone and joint (figure 2d). The proportion of cases with bone and joint tuberculosis increased with increasing age. Female patients were more likely to have bone and joint tuberculosis (ARO, 1.7) than were male patients. No significant differences were found by race/ethnicity or country of origin. Miliary (figure 2e). Patients younger than 15 or older than 65 yr of age were most likely to have miliary tuberculosis. Blacks (ARO, 2.1) and American Indian/Alaskan Natives (ARO, 3.1)were more likely to have miliary tuberculosis than were non-Hispanic whites. No significant differences were found between male and female patients and between patients born in the United States and the foreign-born. Meningeal (figure 2f). Patients younger than 15 yr of age were most likely
TABLE 1 EXTRAPULMONARY TUBERCULOSIS AMONG PATIENTS WITH TUBERCULOSIS BY DEMOGRAPHIC CHARACTERISTICS, UNITED STATES, 1986. REPORTED CASES, UNADJUSTED AND ADJUSTED PROPORTIONS WITH 95% CONFIDENCE INTERVALS
Total· Total in model l Age group
0-14 15-24 25-34 35-44 45-64 65+ Race/ethnicity Non-Hispanic white Hispanic white Black American Indian Asian Sex Male Female Country of origin United States Foreign
Adjusted Proportion (95% C/)
Extrapulmonary Tuberculosis
Pulmonary Tuberculosis
Total
Unadjusted Proportion
3,991 3,942
18,773 18,564
22,764 22,506
17.5 17.5
305 303 831 658 916 929
903 1,408 3,074 2,675 5,139 5,365
1,208 1,711 3,905 3,333 6,055 6,294
25.2 17.7 21.3 19.7 15.1 14.8
24.1 16.1 20.5 20.5 15.7 15.2
(21.6, 26.5) (14.4, 17.9) (19.2, 21.3) (18.6, 21.3) (14.8, 16.7) (14.3,16.1)
1,250 565 1,484 82 561
7,250 2,551 6,522 253 1,988
8,500 3,116 8,006 335 2,549
14.7 18.1 18.5 24.5 22.0
16.1 16.3 18.9 25.2 18.5
(15.3, (15.0, (18.0, (20.5, (17.0,
16.8) 17.6) 19.7) 29.8) 20.0)
0.17 0.0001 0.0001 0.0263
2,220 1,722
12,445 6,119
14,665 7,841
15.1 22.0
15.2 (14.7, 15.8) 21.8 (20.9, 22.7)
0.0001
2,875 1,067
14,484 4,080
17,359 5,147
16.6 20.7
16.9 (16.3, 17.4) 19.7 (18.6, 20.8)
0.0014
• Of the total 22,768 patients, four had no information on site of disease. The 262 patients who had missing information on age, race, ethnicity, sex, or country of origin were excluded.
t
p Value
0.0001 0.34 0.0001 0.0001 0.42
349
EXTRAPULMONARY TUBERCULOSIS IN THE UNITED STATES
Characteristic 85 • 00-14 15-24
134 202 116
25-34 35-44 45-84
335
While. rt-H. Hispanic Black Am. Indian Asian
267 208 450 13 281
Male Female U.S.-born For.-born
560 659 744
------.-------~
I
==i=>.
=iF
I I
228 204
=jeo
~
..
.. [
475
0.2
45-84 While. n-H. Hlapanlc
•
HANS L. RIEDER, DIXIE E. SNIDER, JR., and GEORGE M. CAUTHEN
Introduction
From 1963 to 1986, the number of reported cases of pulmonary tuberculosis in the United States declined from 49,203 to 18,977, an average annual decline of 1070. In contrast, over the same period 01 time, the number of reported extrapulmonary tuberculosis cases declined only 0.9070 annually (figure 1). The failure of extrapulmonary tuberculosis to decline at the same rate as pulmonary tuberculosis has been noted before (1). Possible explanations have included: (1) increased recognition/reporting, (2) overdiagnosis, (3) actual failure to decline, and (4) a combination of these factors (2). It was the purpose of this analysis to describe the demographic characteristics of patients with extrapulmonary tuberculosis in the United States and to compare them with the characteristics of patients with pulmonary tuberculosis. The data from this study suggest one hypothesis to explain the relatively small decline in extrapulmonary tuberculosis over time and several hypotheses to explain the differences in site of disease in various demographically defined groups. Methods In 1986,22,764patients with tuberculosis with known major site of disease were reported to the Centers for Disease Control, of which 3,991 (17.5070) had an extrapulmonary site reported as the major site. After exclusion of 262 patients with incomplete information, 22,506 (98.9070) with known age, race/ethnicity, sex, and country of birth were available for analysis. Patients were divided by major site of disease into pulmonary and eight extrapulmonary categories: lymphatic, pleural, genitourinary, bone and joint, miliary, meningeal, and all other forms combined. Patients were also stratified by age, race/ethnicity, sex, and country of origin (table 1). For each of these demographic characteristics, the stratum with the most cases of pulmonary tuberculosis was arbitrarily chosen as the reference stratum for comparing disease site distributions in terms of relative odds. For example, among female patients, 6,119sites were pulmonary, and 174 were bone and joint as the major site of disease; among male patients, 12,445 siteswerepulmonary and 211 werebone and joint. Thus, the observed odds of bone
SUMMARY From 1963 to 1986, the number of reported cases of pulmonary tuberculosis in the United States declined an average of 5.0% annually, and the number of cases of extrapulmonary tuberculosis declined an average of 0.9% annually over the same period. In 1986, 17.5%of all cases of tuberculosis wereextrapulmonary. Of pUlmonarycases, 63.0% occurred among racial ethnic minorities and the foreign-born, whereas of extrapulmonary cases, the respective proportion was 71.2%. After adjustment for other variables, the proportion of extrapulmonary tuberculosis among all patients with tuberculosis by age was found to be largest In children and generally to decrease with increasing age, larger among black, Asian, and American Indian than among non-Hispanic white patients, larger among female than among male patients, and larger among the foreign-born than among patients born in the United States. The smaller decline in extrapulmonary tuberculosis over the years may be partially due to changes in the demographic characteristics of patients with tuberculosis. Considerable differences in susceptibility to different sites of extrapulmonary tuberculosis by age, race/ethnlcity, sex, and country of origin were found. The reasons for these differences remain AM REV RESPIR DIS 1990; 141:347-351 largely unexplained.
and joint to pulmonary cases was 174/6,119 among female and 211/12,455 among male patients. Using male patients as the reference category, the observed relative odds werethus (174/6,119)/(211/12,445) = 1.68 among female patients relative to male patients, and (211/12,445)/(211/12,445) = 1 among male patients relative to male patients by definition. This can be interpreted as showing that female patients with tuberculosis are 1.68 times more likelyto havebone and joint tuberculosis than are male patients. To isolate the effect of the variable of interest, the observed relativeodds wereadjusted (adjusted relative odds = ARO) to control for the effects of other variables. For example, foreign-born patients with tuberculosis do not have the same age, race/ethnicity, and sex characteristics as do U.S.-born patients; therefore, adjustment for differences in age, race/ethnicity, and sex is necessary to artificially make U.S.-born and foreign-born patients comparable with regard to age, race/ ethnicity, and sex in order to isolate the effect of being foreign-born. Adjusted relative odds were estimated by the maximal likelihood method in a log-linear categorical model of the proportions with disease at each site (3,4). Significance tests and 95070 confidence intervals were also derived from the model. Pulmonary versus all extrapulmonary disease sites combined was similarly modeled using a computer program written by James A. Tonasica, Ph.D. (Johns Hopkins School of Hygiene and Public Health, Baltimore, MD). From this model, adjusted proportions with extrapulmonary disease in various age, race!ethnicity, sex,and country of birth groups could be estimated.
Results
Of the 3,942 extrapulmonary tuberculosis cases (17.5070 of the total 22,506 cases analyzed in the model), 1,219 (30.9070) were lymphatic, 905 (23.0070) werepleural, 469 (11.9070) were genitourinary, 385 (9.8070) were bone and joint, 289 (7.3070) were miliary, 183(4.6070) were meningeal, 132 (3.3070) were peritoneal, and 360 (9.8070) were all other forms combined. Sixty-three percent of pulmonary and 71.2070 of extrapulmonary cases occurred among racial/ethnic minorities and the foreign-born, whereas 37.0070 of pulmonary and 29.8070 of extrapulmonary cases occurred among non-Hispanic whites born in the United States. The proportion of bacteriologically confirmed extrapulmonary cases was 77070.
All Extrapulmonary Forms Combined The age group with the largest propor-
(Received in original form March 6, 1989 and in revised form July 5, 1989) I From the Division of Tuberculosis Control, Centers for Disease Control, Atlanta, Georgia. 2 Presented in part at the Annual Meeting of the American Thoracic Society, Las Vegas, Nevada, May 8-11, 1988. 3 Requests for reprints should be addressed to Technical Information Services, Center for Prevention Services, Mailstop E-06, Centers for Disease Control, 1600 Clifton Road, N.E., Atlanta, GA 30333.
347
348
RIEDER, SNIDER, AND CAUTHEN
Cases
United States, to have extrapulmonary tu berculosis.
(log scale)
::J·· · · ·
~~~m.~n~ry•..•..•..•..•..•
10000
Extrapuimonarv ~
"'
~....
~
.
.
'"
-.
3000
1000 iii
63
66
Ii'
67
i
t
69
ii,
71
73
iii
76
iii
77
79
I
81
iii
83
I
i
I
86
Year
Fig. 1. Reported number of cases of pulmonary and extrapulmonary tuberculosis in the Unites States from 1963 to 1986 (asterisks). The best fitting curves (dotted lines) were obtained by linear regression of the year of report on the logarithm of the number of cases for each year, shown separately for the years before and after the change in reporting criteria in 1975, from which time relapses were to be counted again if the time interval between relapse and previous episode exceeded 12 months.
tion of extrapulmonary tuberculosis cases was children younger than 15 yr of age (table I). By race/ethnicity, American Indians/ Alaskan Natives were most likely to have extrapulmonary tuberculosis; blacks and Asians/Pacific Islanders were more likely than non-Hispanic whites to have extrapulmonary tuberculosis. Female patients were more likely than male patients, and foreign-born patients were more likely than patients born in the
Extrapulmonary Tuberculosis by Site Lymphatic (figure 2a). Patients younger than 15yr of age were the age group most likely (ARO, 7.5) to have lymphatic tuberculosis. Patients younger than 65 yr of age in all age groups were relatively more likely to have lymphatic tuberculosis than patients in the 65 yr and older reference group, but there was no regular pattern by age. Black (ARO, 1.3) and Asian/Pacific Islander patients (ARO, 1.6) were more likely to have lymphatic tuberculosis than were non-Hispanic white patients. Female patients (ARO, 2.2) were more likely to have lymphatic tuberculosis than were male patients. Foreignborn patients were more likely (ARO, 1.7) to have lymphatic tuberculosis than were patients born in the United States. Pleural (figure 2b). Patients younger than 15 yr of age were least likely (ARO, 0.4), and patients-IS to 24 and 34 to 44 yr of age were most likely to have pleural tuberculosis. American Indian/Alaskan Native patients were most likely among all racial/ethnic groups (ARO, 1.8)to have pleural tuberculosis. No significant differences were found between male and female patients, and between patients born in the United States and the foreign-born. Genitourinary (figure 2c). Cases of
genitourinary tuberculosis were least likely to occur in children (ARO, 0.1), and increasingly more likely to occur with increasing age. Cases among blacks (ARO, 0.3) and Asians/Pacific Islanders (ARO, 0.6) were less likely to be genitourinary than cases among non-Hispanic whites, but cases among American Indians/ Alaskan Natives were more likely to be genitourinary (ARO, 2.0). Female (ARO, 1.8)and foreign-born patients (ARO, 1.9) were more likely to have genitourinary tuberculosis than were male and U.S.born patients, respectively. Bone and joint (figure 2d). The proportion of cases with bone and joint tuberculosis increased with increasing age. Female patients were more likely to have bone and joint tuberculosis (ARO, 1.7) than were male patients. No significant differences were found by race/ethnicity or country of origin. Miliary (figure 2e). Patients younger than 15 or older than 65 yr of age were most likely to have miliary tuberculosis. Blacks (ARO, 2.1) and American Indian/Alaskan Natives (ARO, 3.1)were more likely to have miliary tuberculosis than were non-Hispanic whites. No significant differences were found between male and female patients and between patients born in the United States and the foreign-born. Meningeal (figure 2f). Patients younger than 15 yr of age were most likely
TABLE 1 EXTRAPULMONARY TUBERCULOSIS AMONG PATIENTS WITH TUBERCULOSIS BY DEMOGRAPHIC CHARACTERISTICS, UNITED STATES, 1986. REPORTED CASES, UNADJUSTED AND ADJUSTED PROPORTIONS WITH 95% CONFIDENCE INTERVALS
Total· Total in model l Age group
0-14 15-24 25-34 35-44 45-64 65+ Race/ethnicity Non-Hispanic white Hispanic white Black American Indian Asian Sex Male Female Country of origin United States Foreign
Adjusted Proportion (95% C/)
Extrapulmonary Tuberculosis
Pulmonary Tuberculosis
Total
Unadjusted Proportion
3,991 3,942
18,773 18,564
22,764 22,506
17.5 17.5
305 303 831 658 916 929
903 1,408 3,074 2,675 5,139 5,365
1,208 1,711 3,905 3,333 6,055 6,294
25.2 17.7 21.3 19.7 15.1 14.8
24.1 16.1 20.5 20.5 15.7 15.2
(21.6, 26.5) (14.4, 17.9) (19.2, 21.3) (18.6, 21.3) (14.8, 16.7) (14.3,16.1)
1,250 565 1,484 82 561
7,250 2,551 6,522 253 1,988
8,500 3,116 8,006 335 2,549
14.7 18.1 18.5 24.5 22.0
16.1 16.3 18.9 25.2 18.5
(15.3, (15.0, (18.0, (20.5, (17.0,
16.8) 17.6) 19.7) 29.8) 20.0)
0.17 0.0001 0.0001 0.0263
2,220 1,722
12,445 6,119
14,665 7,841
15.1 22.0
15.2 (14.7, 15.8) 21.8 (20.9, 22.7)
0.0001
2,875 1,067
14,484 4,080
17,359 5,147
16.6 20.7
16.9 (16.3, 17.4) 19.7 (18.6, 20.8)
0.0014
• Of the total 22,768 patients, four had no information on site of disease. The 262 patients who had missing information on age, race, ethnicity, sex, or country of origin were excluded.
t
p Value
0.0001 0.34 0.0001 0.0001 0.42
349
EXTRAPULMONARY TUBERCULOSIS IN THE UNITED STATES
Characteristic 85 • 00-14 15-24
134 202 116
25-34 35-44 45-84
335
While. rt-H. Hispanic Black Am. Indian Asian
267 208 450 13 281
Male Female U.S.-born For.-born
560 659 744
------.-------~
I
==i=>.
=iF
I I
228 204
=jeo
~
..
.. [
475
0.2
45-84 While. n-H. Hlapanlc
•
