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Annu. Rev. Med. 1991.42:267-76 Copyright © 1991 by Annual Reviews Inc. All rights reserved
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TUBERCULOSIS IN ELDERLY
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
PERSONS William W. Stead, M.D.
Tuberculosis Program, Arkansas Department of Health, and Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 Asim K. Dutt, M.D.
Medical Service, Alvin C. York Veterans Administration Hospital, Murfreesboro, Tennessee 37130; and Department of Medicine, Meharry School of Medicine, Nashville, Tennessee KEY
WORDS:
nursing homes, tuberculin skin test, nosocomial infection
ABSTRACT
As tuberculosis has been controlled in the western world, it has retreated into enclaves. The largest of these is among persons who are now over age 65, many of whom carry tubercle bacilli in dormant lesions implanted in earlier years and still capable of causing tuberculosis as life forces wane. The diagnosis is all too often not thought of in this age group; as a result, a patient with what was thought to be an episode of bronchitis or bronchopneumonia may die after having exposed a number of young health workers to tuberculosis in a country where it should have been eliminated several years ago. The purpose of this paper is to heighten the index of suspicion of tuberculosis among physicians caring for the elderly. INTRODUCTION
Tuberculosis (TB) presents special problems for the elderly. First, the great longevity of tubercle bacilli permits them to remain viable within a healthy host for many years, presumably safely sequestered within macrophages 267 0066-4219/91/0401--0267$02.00
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
268
STEAD
&
DUTT
and old caseous foci (I). A reaction of 10 mm or more to five units of purified protein derivative of tuberculin (PPD-t) generally indicates that viable bacilli are still present and capable of causing active tuberculosis if circumstances permit, e.g. in failing health, type I diabetes mellitus, pro longed corticosteroid therapy, or other impairment of the immune system. As a result, in the USA the tuberculosis case rate among persons over the age of 65 is higher than in any segment of the population, save for persons with HIV infection (2). Secondly, older persons who eventually live long enough to rid themselves of all residual bacilli may lose their sensitivity to tuberculin and thus lose their considerable protection against becoming infected again (3). Such a person may develop progressive primary TB if exposed to an open case of the disease, as in a nursing home. Thus, among the elderly in nursing homes the TB case rate is 5-10 times higher than in comparable persons living at home (4). In the first third of this century, tuberculin skin test surveys showed that 80% of persons had already been infected by the age of 30 (5). It is the persistence of infection in 15-30% of the survivors of those cohorts that accounts for 90% of the cases of TB that occur in elderly persons. Once it was thought that tubercle bacilli always persisted for the life of the host. However, recent evidence suggests that many elderly persons who were infected in younger years have outlived their tubercle bacilli (3) and are no longer at risk of developing TB unless they are reexposed. When living under normal home conditions where exposure is quite unlikely, such healthy elderly persons rarely develop tuberculosis. But, when such tuberculin-negative persons are exposed to an open case of TB, as in a nursing home, they are again at risk of a new infection. When this happens, a new infection may be established with an 8-12% chance of its developing into clinical TB (6). The TB then is likely to be quite atypical in that it may masquerade as pneumonia, bronchitis, or even congestive heart failure with a pleural effusion (7, 8), rather than as apical infiltration with cavitation. The tuberculosis case rate observed among the elderly in any state is influenced by two factors. It varies directly with the prevalence of the infection in the same cohort in earlier years, and with the diligence with which the infection is looked for among the elderly today. Figure 1 illus trates the first point: the TB case rate in the 25-44 year age group in the northeastern states during the early 1950s was 60.0 per 100,000. Thirty six years later (in 1989), when the cohort was largely over age 65, their average case rate was 14.7 per 100,000 (9). In ten southeastern states, where the case rate in the 25-44 year age group was 65.4 in the early 1950s, it had only fallen to 34.6 in 1989. The great difference in the rate of decline in the case rates in these two sections of the country suggests that other
269
TUBERCULOSIS Change In T8 Case Rates Over 36 Years SE versus NE States 70 60 ..
10
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
a:: .. '" I!II 0 In I-
50 40 30 20 10 1950
1960
1970
1990
1980
Year Figure 1
Comparison of course of annual tuberculosis case rates (cases per 100,000 persons)
from 1953 to 1989. The data for 1953 are for persons in the 25-44 year age group and those for 1989 are for roughly the same cohort 36 years later, when most of them were over the age of 65. The decline in the case rate in the northeastern states is significantly steeper than that in the southeastern states. At this time we have no explanation for this difference.
factors were operative in the ensuing years. About
90%
of the disease in
the elderly results from late progression of infection acquired in earlier
years. The other factor that influences the apparent case rate in any state is the diligence with which tuberculosis is sought in elderly patients. With the decline in incidence of TB, many physicians do not consider the diagnosis as readily as they once did. In Arkansas there has been con siderable emphasis upon the disease in the elderly. Table
case rate for adults from 20 to 65 years Table 1
1
shows that the
was identical in
1987-1989
Annual tuberculosis case rates in adults in Arkansas
versus six surrounding states" measured in cases per 100,000 for
1987-1989b Surroun ding Age
Arkansas
states
20-64
9.9 50.8
10.0 28.5
65+
p 0.1 160.0
N.S.
0.0001
"Louisiana, Mississippi, Missouri, Oklahoma, Tennessee, Texas. from the Centers for Disease Control (9).
b Data
in
270
STEAD & DUTT
Arkansas and in the six surrounding states (Missouri, Oklahoma, Texas, Louisiana, Mississippi, and Tennessee). However, the TB case rate among the elderly in Arkansas is nearly twice that in the surrounding states. It seems likely that the emphasis on TB in the elderly is having an effect upon physicians in Arkansas.
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
THE TUBERCULIN SKIN TEST IN THE ELDERLY
It is widely believed that the tuberculin skin test is of little value in elderly persons. Many physicians assume that most of the elderly would test negative because of anergy, while others recall that most of the elderly were once infected with Mycobacterium tuberculosis in their youth and would be expected still to react to the test. Our studies of about 53,000 residents of the 227 nursing homes in Arkansas (3) have shown that neither school of thought is correct (Table 2). When an elderly person is being examined initially or at the time of admission to a nursing home, it is a good practice to perform a tuberculin skin test to have on record and to get a chest radiograph on those who react positively. Although the TB case rate is much higher among nursing home residents than among elderly persons in general, 80% of all TB cases in the elderly arise among those living at home, largely from recrudescence of old infec tion. About 20% of the cases arise among the 5% who live in nursing homes, as a mixture of old and recently acquired infection. Despite the fact that a positive tuberculin skin test signifies the presence of viable tubercle bacilli, studies have shown that reactors survive sig nificantly longer than nonreactors. The reason is that a positive tuberculin reaction identifies persons who are immunocompetent and thus able to combat a variety of infections and tumors better than those who are immuno-incompetent. However, it is important to realize that only 5-10% of those who fail to react to tuberculin are immuno-incompetent. Figure
Table 2
Risk of tuberculosis by tuberculin status Number
Never positive Previously positive Positive entry Converters
Risk of tuberculosis
%
%
Men
Women
11,584
25,421
18
0.16
590
614
28
4.7
2,073
2,511
58
2.8
53
2.1
360
546
45
12.5
42
7.7
Men
Women 7 13
0.03 2.1
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
TUBERCULOSIS
271
2 shows that tuberculin-negative nursing home residents show a high death rate (of 5-lO%) in the first few months. However, those who survive for 6-12 months are obviously immunocompetent because they then survive as long as those whose immunocompetence is shown by the reaction to tuberculin (3). Since being tuberculin positive affords a distinct protection from "catch ing" the organisms again, it has its advantages. However, it also indicates that the individual still harbors viable tubercle bacilli from the past, which may "come to life" at any time and produce clinical tuberculosis. Thus, it is important to obtain an initial chest radiograph on all reactors to be certain the infection is not already reactivating. In addition, the positive skin test reading should be placed in a prominent place in the medical chart (or posted on the chart cover), as a means of reducing the delay between development of bronchitis or pneumonia and the time sputum is submitted for smear and culture for acid-fast bacilli. The tuberculin test should be read with the ball-point pen technique of Sokal (10) and the result recorded in millimeters of induration (or 0 mm if there is absolutely no reaction). When the result is "negative" « 10 mm Of induration), the test should be repeated with the same dose of antigen
100
eo () z
�
;;;, 1/1
�
15 IL
80
70
80
�
40 0
2
4
6
8
YEARS Figure 2
Survival of nonreactors to tuberculin in comparison with immunocompetent
nursing home residents. Although nonreactors suffer rapid initial loss, those who survive 6-
12 months prove to be immunocompetent by surviving in parallel from that time on.
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
272
STEAD & DUTT
to see if reactivity can be recalled. Such a booster positive test carries the same significance as a test that is positive on the first application. Only by this method can one distinguish a true conversion from a recall or booster reaction, in the event retesting is done after an exposure at a later time. Although few nonreactors to tuberculin develop TB, it should be remem bered that 10--20% of persons who are clinically ill with active TB fail to react to tuberculin. Whenever an elderly tuberculin reactor develops a cough, unexplained loss of weight, or night sweats, TB should be an early consideration. Submission of two sputum specimens for smear and culture for TB early in the course of illness may save a great deal of trouble for all concerned. LATER RETESTING OF NONREACTORS IN NURSING HOMES
When there is suspicion that tuberculosis has spread in a nursing home, all previously nonreactive persons who may have been exposed should be retested, using 5 tuberculin units of PPD and again reading results with the ball-point pen technique. Then, if proper testing of each resident was recorded at the time of entry, it is easy to identify residents with a new infection. Those with new infections generally show a large reaction to 5 units of PPD-an increase of 15 mm or more of induration over the size of the negative tests done at entry (3, 11). Without prior test results, one must consider all such large reactions as conversions because reactions due to old infections are generally smaller. Once all converters have been identified, all tuberculin reactors (whether old or conversions) should have chest radiographs to detect evidence of tuberculosis. In addition, all persons with chronic cough should be x-rayed in order to detect the occasional person who has active TB with a negative tuberculin test. TREATMENT CONSIDERATIONS
Therapy for Active Tuberculosis
Tuberculin reactors with chest radiographs that show lesions suspicious for TB should be treated as having probable active TB. Several sputa should be submitted for smear and culture. If these are positive, the diagnosis is confirmed. However, if they are negative, clinical judgement must be exercised, because new infections commonly shed too few organ isms to be detected by current methods. Therefore, if the patient tolerates the medication satisfactorily and the radiograph shows improvement, we suggest completing the course of therapy.
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TUBERCULOSIS
273
Where activc TB is suspcctcd, thcrapy with a single drug is not satis factory because of the likelihood of developing bacterial resistance to that drug. For this reason, the combination of rifampin (RIF) and isoniazid (INH) is generally recommended, because both drugs are bactericidal and the chance of developing drug resistance is extremely small. The regimen we find most satisfactory is two combination capsules of RIF and INH (Rifamate@) with pyridoxine 50 mg given daily for one month, followed by two Rifamate capsules and two 300-mg tablets of INH twice a week (12). The medication may be given daily for the full period with equal but not superior results. For the last several years we have found that we can reduce the length of therapy when there is adequate evidence that the population of organ isms is small. If there are three negative sputum smears and only the cultures are positive, we stop therapy at six months (13). If three smears and cultures are negative, active TB still may be present but the population of organisms very small, in which situation we have found that therapy for four months is adequate (14).
Monitoring for Drug Toxicity The nurse in charge of each patient who is receiving antituberculous drugs should be acquainted with their side effects, in order that toxicity may be detected beforc irrcparable harm is done. We do not recommend monthly liver function tests because they are so commonly elevated and lead to more confusion than enlightenment. If the patient shows nausea and/or vomiting, the medication should be withheld and blood submitted for liver function tests. If not elevated, the drug(s) are probably not the cause and medication can be restarted when the patient has recovered. If the transaminase is elevated, the patient may be rechallenged with each drug separately after clinical and biochemical recovery, starting with a half dose of each drug for three days and, if tolerated, progressing to the full dose. Over half of the patients with symptoms and elevated transaminase are able to tolerate the medication if it is restarted in this way. If the combination of INH and RIF is not tolerated, another drug should be substituted and therapy completed.
Preventive Therapy Since most tuberculosis in the elderly develops in persons who harbor old infections, it would be desirable to have a method to ensure that recrudescence would not occur. However, studies show that preventive therapy for old reactors is a greater risk than is the 2-3% chance of developing active tuberculosis (6). On the other hand, newly identified conversion of the tuberculin skin
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
274
STEAD & DUTT
test (an increase of 15 mm or more over the previously negative skin test) is associated with a much greater incidence of tuberculosis and constitutes a strong indication for preventive therapy with isoniazid (INH) in a dose of 300 mg/day for 6-9 months. We found that 12 months of such therapy confers a 98.6% protection against TB when compared with converters who are not treated (6). When properly supervised, such therapy is quite safe. However, we observed an incidence of nonfatal toxic hepatitis of 4.5% in about 2000 elderly persons so treated (6). Therefore, monitoring for toxic side effects of the drug is imperative. The most common side effects are loss of appetite and nausea, progressing to vomiting. At that point the drug should be withheld and blood drawn for liver function tests. If the transaminase is elevated to 500 units/liter or more, the drug should not be tried further. On the other hand, if it is modestly elevated, it is appropriate to rechallenge the patient with 150 mg INH (one half tablet) for three days (if tolerated) and then continue with full dose under careful observation. Over 50% of patients tolerate continuation of therapy if managed in this way. It is generally advisable to give pyridoxine in a dose of 25-50 mg daily in elderly persons to prevent neurologic and hematologic side effects of INH.
Late Effects of Preventive Therapy Although hepatitis is the most obvious toxic effect of INH therapy, we examined our data by the life table method to see if the survival of persons who were treated with a year of INH might be shortened for some unknown reason. Figure 3 shows that persons who were treated survived at least as well and perhaps longer than those who would have qualified for therapy but who were not treated (6), The purpose of this graph is only to demonstrate that we did not shorten the life of those we treated, not to argue that INH is a good all-around tonic, SUMMARY
Tuberculosis is still common among elderly persons and is all too often overlooked. Those at risk can usually be detected by the tuberculin skin test. A chest radiograph should be made on all reactors in search of active tuberculosis. If none is found, the patient should be watched for subsequent development of the disease. Therapy with isoniazid and rifampin is quite safe and effective for active TB in elderly persons. Preventive therapy with isoniazid generally is indicated only for elderly persons whose tuberculin skin test conversion signals a newly acquired infection. This is most likely to occur in a nursing home, where exposure to active tuberculosis is not uncommon. Such therapy can be given safely
TUBERCULOSIS
275
0.8
0.8
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
I I61
0.7
Treoted
o.e
0.5
n-1.27e
Not treated n-8S13
0.4 0
2
4
IS
IS
'1'_,..
Figure 3
Survival of nursing home residents who were treated prophylactically with iso
niazid is not impaired. We do not intend to say that their survival is better, only that it was not shortened by the therapy.
if the patient is watched for development of hepatic toxicity and the drug stopped promptly if nausea and vomiting occur.
Literature Cited 1. Stead, W. W. 1967. Pathogenesis of a first episode of chronic pulmonary tuberculosis in man: recrudescence of residuals of the primary infection or exogenous reinfection. Am. Rev. Resp. Dis. 95: 729-45 2. Stead, W. W., Lofgren, J. P. 1983. Medi cal perspective: Does the risk of tubercu losis increase in old age? J. Inject. Dis. 147:951-55 3. Stead, W. W., To, T. 1987. The sig nificance of the tuberculin skin test in elderly persons. Ann. Intern. Med. 107: 837-42 4. Stead W. W. 1987. Why does tuber culosis remain so common among the elderly? Hasp. Pract. (Sept.), pp. 9-10 5. Rich, A. R. 1951. The Pathogenesis oj Tuberculosis, p. 110. Springfield, Ill: Thomas. 2nd ed. 6. Stead, W. W., To, T., Harrison, R. W., .
Abraham, J. H. 1987. 1987. Benefit-risk considerations in preventive treatment for tuberculosis in elderly persons. Ann. Intern. Med. 107: 843-45 7. Stead, W. W., Kerby, G. R., Schlueter, D. P., Jordahl, C. W. 1968. The clinical spectrum of primary tuberculosis in adults: confusion with reinfection in the pathogenesis of chronic tuberculosis. Ann. Intern. Med. 68: 731-45 8. Khan, M. A., Novat, D. M., Bachus, B., Whitcomb, M. E., Brody, J. S., Snider, G. L. 1977. Clinical and roentgeno graphic spectrum of pulmonary tubercu losis in the adult. Am. J. Med. 62: 3138 9. Centers for Disease Control. Tubercu losis in the United States, 1987-89, HHS Pub!. In press. (Courtesy of Dr. George Cauthen, Division of TB Elimination, Centers for Disease Control)
276
STEAD & DUTT
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
10. Sokal, 1. E. 1975. Measurement of delayed skin-test responses. N. Engl. J. Med. 293: 501-2 11. Centers for Disease Control. 1990. Pre vention and control of tuberculosis in facilities providing long-term care to the elderly. Morbid. Mortal. Wkly. Rep. Suppl., Vol. 39, No. RR-IO 12. Dutt, A. K., Stead, W. W. 1982. Medical perspective: Present chemotherapy for tuberculosis. J. Infec t . Dis. 146: 698-704
13. Dutt, A. K., Moers, D. 1., Stead, W. W. 1990. Smear-negative, culture-positive tuberculosis: Six-month chemotherapy with isoniazid and rifampin. Am. Rev.
Respir. Dis. 141: 1232-35
14. Dutt, A. K., Moers, D. 1., Stead, W. W. 1989. Smear- and culture-negative pulmonary tuberculosis: four-month short course chemotherapy. Am. Rev. Respir. Dis. 139: 867-70
Annu. Rev. Med. 1991.42:267-76 Copyright © 1991 by Annual Reviews Inc. All rights reserved
Further
Quick links to online content
TUBERCULOSIS IN ELDERLY
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
PERSONS William W. Stead, M.D.
Tuberculosis Program, Arkansas Department of Health, and Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 Asim K. Dutt, M.D.
Medical Service, Alvin C. York Veterans Administration Hospital, Murfreesboro, Tennessee 37130; and Department of Medicine, Meharry School of Medicine, Nashville, Tennessee KEY
WORDS:
nursing homes, tuberculin skin test, nosocomial infection
ABSTRACT
As tuberculosis has been controlled in the western world, it has retreated into enclaves. The largest of these is among persons who are now over age 65, many of whom carry tubercle bacilli in dormant lesions implanted in earlier years and still capable of causing tuberculosis as life forces wane. The diagnosis is all too often not thought of in this age group; as a result, a patient with what was thought to be an episode of bronchitis or bronchopneumonia may die after having exposed a number of young health workers to tuberculosis in a country where it should have been eliminated several years ago. The purpose of this paper is to heighten the index of suspicion of tuberculosis among physicians caring for the elderly. INTRODUCTION
Tuberculosis (TB) presents special problems for the elderly. First, the great longevity of tubercle bacilli permits them to remain viable within a healthy host for many years, presumably safely sequestered within macrophages 267 0066-4219/91/0401--0267$02.00
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
268
STEAD
&
DUTT
and old caseous foci (I). A reaction of 10 mm or more to five units of purified protein derivative of tuberculin (PPD-t) generally indicates that viable bacilli are still present and capable of causing active tuberculosis if circumstances permit, e.g. in failing health, type I diabetes mellitus, pro longed corticosteroid therapy, or other impairment of the immune system. As a result, in the USA the tuberculosis case rate among persons over the age of 65 is higher than in any segment of the population, save for persons with HIV infection (2). Secondly, older persons who eventually live long enough to rid themselves of all residual bacilli may lose their sensitivity to tuberculin and thus lose their considerable protection against becoming infected again (3). Such a person may develop progressive primary TB if exposed to an open case of the disease, as in a nursing home. Thus, among the elderly in nursing homes the TB case rate is 5-10 times higher than in comparable persons living at home (4). In the first third of this century, tuberculin skin test surveys showed that 80% of persons had already been infected by the age of 30 (5). It is the persistence of infection in 15-30% of the survivors of those cohorts that accounts for 90% of the cases of TB that occur in elderly persons. Once it was thought that tubercle bacilli always persisted for the life of the host. However, recent evidence suggests that many elderly persons who were infected in younger years have outlived their tubercle bacilli (3) and are no longer at risk of developing TB unless they are reexposed. When living under normal home conditions where exposure is quite unlikely, such healthy elderly persons rarely develop tuberculosis. But, when such tuberculin-negative persons are exposed to an open case of TB, as in a nursing home, they are again at risk of a new infection. When this happens, a new infection may be established with an 8-12% chance of its developing into clinical TB (6). The TB then is likely to be quite atypical in that it may masquerade as pneumonia, bronchitis, or even congestive heart failure with a pleural effusion (7, 8), rather than as apical infiltration with cavitation. The tuberculosis case rate observed among the elderly in any state is influenced by two factors. It varies directly with the prevalence of the infection in the same cohort in earlier years, and with the diligence with which the infection is looked for among the elderly today. Figure 1 illus trates the first point: the TB case rate in the 25-44 year age group in the northeastern states during the early 1950s was 60.0 per 100,000. Thirty six years later (in 1989), when the cohort was largely over age 65, their average case rate was 14.7 per 100,000 (9). In ten southeastern states, where the case rate in the 25-44 year age group was 65.4 in the early 1950s, it had only fallen to 34.6 in 1989. The great difference in the rate of decline in the case rates in these two sections of the country suggests that other
269
TUBERCULOSIS Change In T8 Case Rates Over 36 Years SE versus NE States 70 60 ..
10
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
a:: .. '" I!II 0 In I-
50 40 30 20 10 1950
1960
1970
1990
1980
Year Figure 1
Comparison of course of annual tuberculosis case rates (cases per 100,000 persons)
from 1953 to 1989. The data for 1953 are for persons in the 25-44 year age group and those for 1989 are for roughly the same cohort 36 years later, when most of them were over the age of 65. The decline in the case rate in the northeastern states is significantly steeper than that in the southeastern states. At this time we have no explanation for this difference.
factors were operative in the ensuing years. About
90%
of the disease in
the elderly results from late progression of infection acquired in earlier
years. The other factor that influences the apparent case rate in any state is the diligence with which tuberculosis is sought in elderly patients. With the decline in incidence of TB, many physicians do not consider the diagnosis as readily as they once did. In Arkansas there has been con siderable emphasis upon the disease in the elderly. Table
case rate for adults from 20 to 65 years Table 1
1
shows that the
was identical in
1987-1989
Annual tuberculosis case rates in adults in Arkansas
versus six surrounding states" measured in cases per 100,000 for
1987-1989b Surroun ding Age
Arkansas
states
20-64
9.9 50.8
10.0 28.5
65+
p 0.1 160.0
N.S.
0.0001
"Louisiana, Mississippi, Missouri, Oklahoma, Tennessee, Texas. from the Centers for Disease Control (9).
b Data
in
270
STEAD & DUTT
Arkansas and in the six surrounding states (Missouri, Oklahoma, Texas, Louisiana, Mississippi, and Tennessee). However, the TB case rate among the elderly in Arkansas is nearly twice that in the surrounding states. It seems likely that the emphasis on TB in the elderly is having an effect upon physicians in Arkansas.
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
THE TUBERCULIN SKIN TEST IN THE ELDERLY
It is widely believed that the tuberculin skin test is of little value in elderly persons. Many physicians assume that most of the elderly would test negative because of anergy, while others recall that most of the elderly were once infected with Mycobacterium tuberculosis in their youth and would be expected still to react to the test. Our studies of about 53,000 residents of the 227 nursing homes in Arkansas (3) have shown that neither school of thought is correct (Table 2). When an elderly person is being examined initially or at the time of admission to a nursing home, it is a good practice to perform a tuberculin skin test to have on record and to get a chest radiograph on those who react positively. Although the TB case rate is much higher among nursing home residents than among elderly persons in general, 80% of all TB cases in the elderly arise among those living at home, largely from recrudescence of old infec tion. About 20% of the cases arise among the 5% who live in nursing homes, as a mixture of old and recently acquired infection. Despite the fact that a positive tuberculin skin test signifies the presence of viable tubercle bacilli, studies have shown that reactors survive sig nificantly longer than nonreactors. The reason is that a positive tuberculin reaction identifies persons who are immunocompetent and thus able to combat a variety of infections and tumors better than those who are immuno-incompetent. However, it is important to realize that only 5-10% of those who fail to react to tuberculin are immuno-incompetent. Figure
Table 2
Risk of tuberculosis by tuberculin status Number
Never positive Previously positive Positive entry Converters
Risk of tuberculosis
%
%
Men
Women
11,584
25,421
18
0.16
590
614
28
4.7
2,073
2,511
58
2.8
53
2.1
360
546
45
12.5
42
7.7
Men
Women 7 13
0.03 2.1
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
TUBERCULOSIS
271
2 shows that tuberculin-negative nursing home residents show a high death rate (of 5-lO%) in the first few months. However, those who survive for 6-12 months are obviously immunocompetent because they then survive as long as those whose immunocompetence is shown by the reaction to tuberculin (3). Since being tuberculin positive affords a distinct protection from "catch ing" the organisms again, it has its advantages. However, it also indicates that the individual still harbors viable tubercle bacilli from the past, which may "come to life" at any time and produce clinical tuberculosis. Thus, it is important to obtain an initial chest radiograph on all reactors to be certain the infection is not already reactivating. In addition, the positive skin test reading should be placed in a prominent place in the medical chart (or posted on the chart cover), as a means of reducing the delay between development of bronchitis or pneumonia and the time sputum is submitted for smear and culture for acid-fast bacilli. The tuberculin test should be read with the ball-point pen technique of Sokal (10) and the result recorded in millimeters of induration (or 0 mm if there is absolutely no reaction). When the result is "negative" « 10 mm Of induration), the test should be repeated with the same dose of antigen
100
eo () z
�
;;;, 1/1
�
15 IL
80
70
80
�
40 0
2
4
6
8
YEARS Figure 2
Survival of nonreactors to tuberculin in comparison with immunocompetent
nursing home residents. Although nonreactors suffer rapid initial loss, those who survive 6-
12 months prove to be immunocompetent by surviving in parallel from that time on.
Annu. Rev. Med. 1991.42:267-276. Downloaded from www.annualreviews.org by North Carolina State University on 09/25/13. For personal use only.
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to see if reactivity can be recalled. Such a booster positive test carries the same significance as a test that is positive on the first application. Only by this method can one distinguish a true conversion from a recall or booster reaction, in the event retesting is done after an exposure at a later time. Although few nonreactors to tuberculin develop TB, it should be remem bered that 10--20% of persons who are clinically ill with active TB fail to react to tuberculin. Whenever an elderly tuberculin reactor develops a cough, unexplained loss of weight, or night sweats, TB should be an early consideration. Submission of two sputum specimens for smear and culture for TB early in the course of illness may save a great deal of trouble for all concerned. LATER RETESTING OF NONREACTORS IN NURSING HOMES
When there is suspicion that tuberculosis has spread in a nursing home, all previously nonreactive persons who may have been exposed should be retested, using 5 tuberculin units of PPD and again reading results with the ball-point pen technique. Then, if proper testing of each resident was recorded at the time of entry, it is easy to identify residents with a new infection. Those with new infections generally show a large reaction to 5 units of PPD-an increase of 15 mm or more of induration over the size of the negative tests done at entry (3, 11). Without prior test results, one must consider all such large reactions as conversions because reactions due to old infections are generally smaller. Once all converters have been identified, all tuberculin reactors (whether old or conversions) should have chest radiographs to detect evidence of tuberculosis. In addition, all persons with chronic cough should be x-rayed in order to detect the occasional person who has active TB with a negative tuberculin test. TREATMENT CONSIDERATIONS
Therapy for Active Tuberculosis
Tuberculin reactors with chest radiographs that show lesions suspicious for TB should be treated as having probable active TB. Several sputa should be submitted for smear and culture. If these are positive, the diagnosis is confirmed. However, if they are negative, clinical judgement must be exercised, because new infections commonly shed too few organ isms to be detected by current methods. Therefore, if the patient tolerates the medication satisfactorily and the radiograph shows improvement, we suggest completing the course of therapy.
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Where activc TB is suspcctcd, thcrapy with a single drug is not satis factory because of the likelihood of developing bacterial resistance to that drug. For this reason, the combination of rifampin (RIF) and isoniazid (INH) is generally recommended, because both drugs are bactericidal and the chance of developing drug resistance is extremely small. The regimen we find most satisfactory is two combination capsules of RIF and INH (Rifamate@) with pyridoxine 50 mg given daily for one month, followed by two Rifamate capsules and two 300-mg tablets of INH twice a week (12). The medication may be given daily for the full period with equal but not superior results. For the last several years we have found that we can reduce the length of therapy when there is adequate evidence that the population of organ isms is small. If there are three negative sputum smears and only the cultures are positive, we stop therapy at six months (13). If three smears and cultures are negative, active TB still may be present but the population of organisms very small, in which situation we have found that therapy for four months is adequate (14).
Monitoring for Drug Toxicity The nurse in charge of each patient who is receiving antituberculous drugs should be acquainted with their side effects, in order that toxicity may be detected beforc irrcparable harm is done. We do not recommend monthly liver function tests because they are so commonly elevated and lead to more confusion than enlightenment. If the patient shows nausea and/or vomiting, the medication should be withheld and blood submitted for liver function tests. If not elevated, the drug(s) are probably not the cause and medication can be restarted when the patient has recovered. If the transaminase is elevated, the patient may be rechallenged with each drug separately after clinical and biochemical recovery, starting with a half dose of each drug for three days and, if tolerated, progressing to the full dose. Over half of the patients with symptoms and elevated transaminase are able to tolerate the medication if it is restarted in this way. If the combination of INH and RIF is not tolerated, another drug should be substituted and therapy completed.
Preventive Therapy Since most tuberculosis in the elderly develops in persons who harbor old infections, it would be desirable to have a method to ensure that recrudescence would not occur. However, studies show that preventive therapy for old reactors is a greater risk than is the 2-3% chance of developing active tuberculosis (6). On the other hand, newly identified conversion of the tuberculin skin
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test (an increase of 15 mm or more over the previously negative skin test) is associated with a much greater incidence of tuberculosis and constitutes a strong indication for preventive therapy with isoniazid (INH) in a dose of 300 mg/day for 6-9 months. We found that 12 months of such therapy confers a 98.6% protection against TB when compared with converters who are not treated (6). When properly supervised, such therapy is quite safe. However, we observed an incidence of nonfatal toxic hepatitis of 4.5% in about 2000 elderly persons so treated (6). Therefore, monitoring for toxic side effects of the drug is imperative. The most common side effects are loss of appetite and nausea, progressing to vomiting. At that point the drug should be withheld and blood drawn for liver function tests. If the transaminase is elevated to 500 units/liter or more, the drug should not be tried further. On the other hand, if it is modestly elevated, it is appropriate to rechallenge the patient with 150 mg INH (one half tablet) for three days (if tolerated) and then continue with full dose under careful observation. Over 50% of patients tolerate continuation of therapy if managed in this way. It is generally advisable to give pyridoxine in a dose of 25-50 mg daily in elderly persons to prevent neurologic and hematologic side effects of INH.
Late Effects of Preventive Therapy Although hepatitis is the most obvious toxic effect of INH therapy, we examined our data by the life table method to see if the survival of persons who were treated with a year of INH might be shortened for some unknown reason. Figure 3 shows that persons who were treated survived at least as well and perhaps longer than those who would have qualified for therapy but who were not treated (6), The purpose of this graph is only to demonstrate that we did not shorten the life of those we treated, not to argue that INH is a good all-around tonic, SUMMARY
Tuberculosis is still common among elderly persons and is all too often overlooked. Those at risk can usually be detected by the tuberculin skin test. A chest radiograph should be made on all reactors in search of active tuberculosis. If none is found, the patient should be watched for subsequent development of the disease. Therapy with isoniazid and rifampin is quite safe and effective for active TB in elderly persons. Preventive therapy with isoniazid generally is indicated only for elderly persons whose tuberculin skin test conversion signals a newly acquired infection. This is most likely to occur in a nursing home, where exposure to active tuberculosis is not uncommon. Such therapy can be given safely
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Survival of nursing home residents who were treated prophylactically with iso
niazid is not impaired. We do not intend to say that their survival is better, only that it was not shortened by the therapy.
if the patient is watched for development of hepatic toxicity and the drug stopped promptly if nausea and vomiting occur.
Literature Cited 1. Stead, W. W. 1967. Pathogenesis of a first episode of chronic pulmonary tuberculosis in man: recrudescence of residuals of the primary infection or exogenous reinfection. Am. Rev. Resp. Dis. 95: 729-45 2. Stead, W. W., Lofgren, J. P. 1983. Medi cal perspective: Does the risk of tubercu losis increase in old age? J. Inject. Dis. 147:951-55 3. Stead, W. W., To, T. 1987. The sig nificance of the tuberculin skin test in elderly persons. Ann. Intern. Med. 107: 837-42 4. Stead W. W. 1987. Why does tuber culosis remain so common among the elderly? Hasp. Pract. (Sept.), pp. 9-10 5. Rich, A. R. 1951. The Pathogenesis oj Tuberculosis, p. 110. Springfield, Ill: Thomas. 2nd ed. 6. Stead, W. W., To, T., Harrison, R. W., .
Abraham, J. H. 1987. 1987. Benefit-risk considerations in preventive treatment for tuberculosis in elderly persons. Ann. Intern. Med. 107: 843-45 7. Stead, W. W., Kerby, G. R., Schlueter, D. P., Jordahl, C. W. 1968. The clinical spectrum of primary tuberculosis in adults: confusion with reinfection in the pathogenesis of chronic tuberculosis. Ann. Intern. Med. 68: 731-45 8. Khan, M. A., Novat, D. M., Bachus, B., Whitcomb, M. E., Brody, J. S., Snider, G. L. 1977. Clinical and roentgeno graphic spectrum of pulmonary tubercu losis in the adult. Am. J. Med. 62: 3138 9. Centers for Disease Control. Tubercu losis in the United States, 1987-89, HHS Pub!. In press. (Courtesy of Dr. George Cauthen, Division of TB Elimination, Centers for Disease Control)
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10. Sokal, 1. E. 1975. Measurement of delayed skin-test responses. N. Engl. J. Med. 293: 501-2 11. Centers for Disease Control. 1990. Pre vention and control of tuberculosis in facilities providing long-term care to the elderly. Morbid. Mortal. Wkly. Rep. Suppl., Vol. 39, No. RR-IO 12. Dutt, A. K., Stead, W. W. 1982. Medical perspective: Present chemotherapy for tuberculosis. J. Infec t . Dis. 146: 698-704
13. Dutt, A. K., Moers, D. 1., Stead, W. W. 1990. Smear-negative, culture-positive tuberculosis: Six-month chemotherapy with isoniazid and rifampin. Am. Rev.
Respir. Dis. 141: 1232-35
14. Dutt, A. K., Moers, D. 1., Stead, W. W. 1989. Smear- and culture-negative pulmonary tuberculosis: four-month short course chemotherapy. Am. Rev. Respir. Dis. 139: 867-70
