The Ottawa County Project: A Report of a Tuberculosis Screening Project in a Small Mining Community RICHARD M. BURKE, MD, L. PAUL SCHWARTZ, MPH, AND DIXIE E. SNIDER, JR., MD
Abstract: Following a retrospective review of tuberculosis cases reported from Ottawa County, Oklahoma, from 1969 through 1973, a selective tuberculosis screening project was implemented. Screening of a "target group" of the population, 519 former miners, -50 years of age, resulted in the discovery of abnormal chest X-rays in 182; (103 with silicosis, 36 with silicotuberculosis, 12 with inactive tuberculosis, and 31 with other abnormalities). Eighty-five of these persons had positive tuberculin skin tests. Preventive therapy was recommended for 50, and 36 completed the prescribed course of treatment. Eight new bacteriologically confirmed cases of tuberculosis were found and treated.
A large number of persons (1,904) residing in the same area who were not part of the target group were also screened for tuberculosis. This group contained a large number of positive tuberculin reactors but very few were candidates for isoniazid preventive therapy. Thirteen persons in this group had abnormal chest Xrays consistent with inactive tuberculosis but 12 had been identified and given preventive therapy before the project began. These data suggest that selective approaches to screening for tuberculosis in a community which are based on an in-depth retrospective review of the tuberculosis case register can be highly successful. (Am. J. Public Health 69:340-347, 1979.)
Tuberculosis persists as a significant public health problem as evidenced by the fact that over 30,000 new cases were reported in the United States during 1976.1 Because of the declining incidence of tuberculosis, however, efficient tuberculosis control programs today no longer utilize the mass campaigns of the past aimed at screening large portions of the population. Since tuberculosis cases are not evenly distributed throughout the population, methods for identifying subgroups of the population which are at high risk of developing tuberculosis must be found so that the individuals in these groups can be screened for the presence of tuberculosis and/or tuberculous infection and given appropriate therapy. Analysis of the information collected for several years by the Tuberculosis and Respiratory Disease Division, Oklahoma State Department of Health, concerning tuberculosis
cases occurring in Ottawa County, Oklahoma, suggested that this County contained a subpopulation at high risk of developing tuberculosis. The data further suggested that a significant contribution toward reducing mortality and morbidity from tuberculosis could be made by conducting a selective tuberculosis screening project in the County. The development, implementation, conduct, and results of this project are the subject of this report.
From the Tuberculosis and Respiratory Disease Division, Oklahoma State Department of Health, Oklahoma City. Dr. Snider is presently with the Tuberculosis Control Division, Bureau of State Services, CDC. Address reprint requests to Technical Information Services, Bureau of State Services, Center for Disease Control, Atlanta, GA 30333. This paper, submitted to the Journal March 7, 1978, was revised and accepted for publication July 6, 1978. 340
Materials and Methods Background The Tuberculosis and Respiratory Disease Division, Oklahoma State Department of Health, was aware of the high incidence of tuberculosis in Ottawa County for many years (Figure 1). The Division knew that many of the cases of tuberculosis diagnosed in Ottawa County had coexisting silicosis. This was not surprising since this area was part of the so-called Tri-State Mining District where extensive lead and zinc mining operations were conducted during the first half of the century. Although mining operations had been discontinued, the Division assumed that a number of the curAJPH April 1979, Vol. 69, No. 4
TBc SCREENING PROJECT IN MINING COMMUNITY 500
more striking when their average annual new active case rates were compared. Using the 1970 census population as the base population upon which to calculate rates, the "Picher Area" was found to have an average annual new case rate of 98.1 per 100,000 population; a rate nearly three times that of the County as a whole.
480
° 0.
380 360
0 a.
340
o -
320 300
I--
1280
260 240 220
200
180
OTTAWA
160 140 120
100 80 60 40
OKLAHOMA
20
1945
1950
1955
1955
1960
1970
1915
YEAR
FIGURE 1-New Active TB Case Rates-Ottawa County and State of Oklahoma 1944-1975
rent residents of Ottawa County were former miners, some of whom had silicosis. In order to gather more information about the tuberculosis problem in Ottawa County, the Tuberculosis Case Register at the State Department of Health was searched for all new active* tuberculosis cases reported in the County between January 1, 1969, and January 1, 1974. A total of 51 new active cases of tuberculosis were found. Thirty-six (70.6 per cent) of the 51 patients resided in the "Picher Area"-an area where extensive "hard-rock" mining occurred previously. Thirty-one of these 36 persons were 2 50 years of age; 29 were male and 7 were female. Twenty (39 per cent) of the 51 cases had silicotuberculosis and 17 of these 20 resided in the Picher Area. All 17 were males, 15 of whom were 2 50 years of age. The differences in the incidence of tuberculosis among the various communities in Ottawa County became even *At the time of this study recent changes in the diagnostic standards and classification of tuberculosis2 had not been implemented. Therefore, the terms "active" and "inactive" were used to classify these patients.
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Project Design, Implementation, and Conduct In view of these findings, we felt that a selective rather than a mass tuberculosis screening project, in the Picher Area, would be the most efficient approach to reducing tuberculosis morbidity in the County. The target group initially selected for screening were males 50 years of age and over who lived in the Picher Area and who had a history of having worked in the mining industry. However, from discussions with residents of the area, it became apparent that the project could not be limited to this target group. A few of the former miners were known to have moved into another part of the County, particularly the City of Miami. Therefore, former miners residing anywhere in the County were invited through newspaper articles, radio spots, posters, etc., to participate in the project. There was also a great deal of local concern that the project might stigmatize the target group unless a broader base of support were generated. Accordingly, emphasis was placed on the tuberculosis problem in the whole Picher community, and arrangements were made for two community workers to conduct a house-to-house canvass of the entire Picher Area. Their responsibilities included obtaining medical histories relevant to tuberculosis and silicosis, and administering tuberculin skin tests to persons in the target group and others interested in participating in the screening program. All skin tests were administered on the volar surface of the forearm with 5 TU of Tween-stabilized, PPD-T using the Mantoux technique. All skin tests were read by project staff members 48-96 hours after administration. Only the transverse diameter of induration was read and recorded. Induration of 10 mm or more was considered positive. All men received a posterior-anterior chest X-ray regardless of the tuberculin skin test results, while only those women whose skin tests were read as 10 mm or greater were X-rayed. Two sputum specimens for smear and culture were obtained from all patients who gave a history of a chronic productive cough (> 2 weeks duration) and from all persons with radiographic findings compatible with tuberculosis and/ or silicosis. If necessary, sputum production was induced with ultrasonic aerosol nebulizer using isotonic saline solution. Specimens were processed by the Bureau of Laboratories, Oklahoma State Department of Health, according to established procedures.3 X-rays were reviewed by the staff physician in charge of the project. The diagnosis of silicosis was based on the typical radiographic findings of pneumoconiosis4 in patients who gave a history of having worked in a dusty mining environment for a minimum of three years. The diagnosis of active tuberculosis was based on the finding of at least one positive culture for M. tuberculosis from patients with clinical and/or radiographic evidence of progressive disease. The diagnosis of inactive tuberculosis 341
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was based either on a documented history of culture-proven tuberculosis or on the finding of a positive tuberculin skin test in patients with negative cultures who had radiographic changes compatible with nonprogressive tuberculosis and/or silicotuberculosis. In the absence of a documented past history of culture-proven tuberculosis, only those silicotic patients with positive skin tests who had extensive upper lobe involvement were classified as having inactive silicotuberculosis. Thus, the frequency of inactive tuberculosis in this population may have been somewhat underestimated.
Results During the canvassing process, the community workers identified 519 persons in the target group, i.e., males 50 years of age or over with a mining history who lived in the Picher area. Figure 2 shows the results of attempts to screen this target group. A total of 367 persons in the target group (71 per cent) participated in the project (93 of the 152 persons who did not participate had already received adequate treatment or had been examined for tuberculosis during the previous two years). Thus, only 59 persons (11 per cent) in the target group of 519 who "should have been" screened refused to participate. Ninety per cent of those in the target group who participated in the project were initially screened by chest X-ray. Fifty-five per cent of these persons had abnormal X-rays, most of them compatible with silicosis and/or tuberculosis. Of the 182 persons with abnormal chest X-rays, 81 per cent received a tuberculin skin test. Thirty-one of the 34 persons not skin tested had a history of a positive test usually associated with a history of tuberculosis; two had recently had a negative tuberculin test; and one refused skin testing. Eighty-five (57 per cent) of the 148 persons with abnormal X-rays had positive skin tests and preventive therapy with isoniazid (300 mg daily for one year) was prescribed for 50 who had abnormal X-rays compatible with silicosis and/or inactive tuberculosis.** Thirty-six (72 per cent) of the 50 persons placed on INH completed the prescribed course of therapy while 14 (28 per cent) prematurely discontinued (see Figure 2). The incidence of adverse reactions resulting in discontinuance of therapy was high in this older age group (7 out of 50 or 14 per cent). However, only one patient was withdrawn from the study because of suspected INH-related hepatitis. Most patients discontinued therapy after experiencing less serious adverse reactions such as headache, fatigue, anorexia, nausea, vomiting, dizziness, rash, chills, and malaise.*** **In the judgment of the staff physician, preventive therapy was contraindicated in 27 persons because of their age (> 35 years old) and because none had X-ray abnormalities suggestive of silicosis and/or tuberculosis (see reference 5). Preventive therapy was contraindicated in eight because of the presence of active disease. ***A relationship between isoniazid administration and these symptoms was suspected in all cases but was not proven by re-challenging with isoniazid. 342
A significant outcome of this screening project was the finding of eight new bacteriologically proven cases of tuberculosis. All of these patients had coexisting silicosis, all were white males, their mean age was 65 and the mean length of their mining experience was 28 years. All had been previously informed of an abnormality on their chest X-ray. Most had visited private physicians in recent years but the diagnosis of tuberculosis had not been made previously. From interviewing these eight new active cases of tuberculosis, 40 contacts were identified. Three of these contacts were 15 years of age or less. Fourteen contacts had positive tuberculin skin tests. Ten of these (including the three children) were placed on preventive treatment. Preventive therapy was felt to be contraindicated in four persons because of their advanced age and the belief that they had remote rather than recent infection. No new cases of tuberculosis were identified as a result of contact investigation. During the canvassing of the target area, the community workers obtained information on 1,904 other persons (in addition to the 519 persons identified in the target group) residing in the Picher area. The results of screening activities among this group is shown in Figure 3. Of the 1,904 persons who gave information to the canvassers, 1,203 (63 per cent) were skin tested. Of those skin tested, 25 per cent had positive reactions. All persons with positive reactions were X-rayed and five cases of silicosis and six cases of inactive tuberculosis were identified. Four of the five silicosis cases were recommended for preventive treatment. Two of these persons died of unrelated illnesses before completing preventive therapy and two discontinued it due to adverse reactions. Of the six inactive tuberculosis cases, five had received preventive therapy before the project began and one completed therapy during the project. Among those who were not skin tested, seven cases of inactive tuberculosis were identified. However, all seven had received treatment prior to the beginning of the project. The number of new active cases of tuberculosis reported in Ottawa County each year from 1969 through 1977 is shown in Figure 4. During calendar year 1976 (the year the project was completed), only five new cases of tuberculosis were reported (including two cases of silicotuberculosis). This was the smallest annual number of cases ever reported in the County. During 1977, however, there were 11 new tuberculosis cases in the County, two with co-existing silicosis. Thus, since the termination of the project a total of 16 new tuberculosis cases have been reported from Ottawa County. Four of these cases are of particular interest because they occurred among persons in the target group who participated in the project. A brief resume of each of these patients is given in the Appendix.
Discussion The decision to conduct this tuberculosis screening project in a community of former miners was based on three assumptions: 1) that a large proportion of these miners would be found to have silicosis; 2) that the prevalence of AJPH April 1979, Vol. 69, No. 4
TBc SCREENING PROJECT IN MINING COMMUNITY
FIGURE 2 -Ottawa County Project-Results of Screening among the "Target Group"
tuberculosis is unusually high among miners or former miners with silicosis; and 3) that the incidence of tuberculosis in this population could be substantially reduced by giving isoniazid preventive therapy (300 mg daily for 12 months) to positive tuberculin reactors with abnormal chest X-rays compatible with silicosis and/or inactive silicotuberculosis. The results of our screening activities among the target group of 519 former miners confirm that our first assumption was correct. Of the 330 former miners in the target group who received a chest X-ray, 139 (42 per cent) showed evidence of silicosis or silicotuberculosis. The literature is replete with references in support of our second assumption, i.e., that there is an increased frequency of tuberculosis among persons with silicosis6-20. In AJPH April 1979, Vol. 69, No. 4
our target group, eight new cases of tuberculosis (all with coexisting silicosis) were discovered among 367 persons screened in a two-year interval. This represents a new case rate qf 1,090 per 100,000 persons screened per year. In contrast, the case rate for the entiie County was 34 per 100,000 per year between 1969 and 1974. Thus, the results of the project also confirmed the fact that tuberculosis and silicosis are frequently coexistent. The frequency with which tuberculosis occurs among silicosis patients may vary depending upon: 1) the prevalence of tuberculous infection in the population; 2) the prevalence of tuberculosis in the surrounding population; 3) the stage and type of silicosis; 4) the age and general health of the population (e.g., nutritional status, presence of other 343
BURKE, ET AL.
FIGURE 3-Ottawa County Project-Screening of Persons Outside the "Target Group"
medical conditions); 5) the preventive measures applied; and 6) the diagnostic methods used and the intensity with which they are applied. The prevalence of infection in the entire Ottawa County target group is unknown since skin tests were generally performed only if the participant's chest X-ray was abnormal. Fifty-seven per cent of those with abnormal X-rays who were skin tested had a tuberculin reaction of 10 mm or more indicating that a significant reservoir of tuberculous infection exists in the population. The prevalence of infection among persons in the surrounding population (those outside the target group) was much lower; 303 of 1,203 persons skin tested (25 per cent) had positive reactions. These data suggest that most of the tuberculosis occurring in this population resulted from reactivation of a remote, latent infection in a member of the target group rather than from exogenous
re-infection. The prevalence of tuberculosis among former miners in Ottawa County may be particularly high because many are suffering from the more advanced stages of "pure" silicosis. Bruce has shown that the prevalence of complicating tuberculosis is higher among persons with the more advanced stages of silicosis.20 He also concluded that tuberculosis is more common among persons with "pure" silicosis than among those with mixed-dust pneumoconiosis. This population of former miners would also be expected to be at higher risk of tuberculosis because of their advanced age and an associated increase in the number of concomitant medical conditions. Tuberculosis could have been prevented in this population in a variety of ways. Of obvious importance in this regard is the prevention of the silicotic process itself. This can 344
be accomplished by: wetting down mine shafts to prevent the generation of dusts, requiring workers exposed to silica dust to wear effective masks or hoods, instituting effective ventilation, and limiting the amount of time individual workers are exposed to dust. In the past, BCG vaccination of tuberculin-negative silicotics was also recommended, but current opinion21-23 favors the notion that BCG vaccination of silicotics is contraindicated. Among silicotics with positive tuberculin tests, BCG vaccination would be expected to have no benefit. Therefore, the use of isoniazid preventive therapy in this group has been recommended.5 18, 21-24 In contrast to the extensive preventive therapy trials conducted among other groups (contacts, persons with fibrotic lesions, etc.), there are no large controlled trials of the use of INH preventive therapy among silicotics. We were able to find only one brief report concerning the efficacy of INH preventive therapy among silicotics in the English literature. Monaco"8 reported a trial among 811 silicotics with positive tuberculin reactions treated with INH and a group of 411 silicotics with positive reactions (not matched geographically) left untreated as controls. The INH (10 mg/Kg/day) was given for three months every six months for two years or longer. Over a five-year follow-up period, tuberculosis morbidity was 0.73 per cent among the treated group and 10.21 per cent among the controls. Thus, the treated group had a 14-fold reduction in new cases of tuberculosis. However, because this was not a randomized trial, these results must be interpreted with caution. The non-English literature contains several reports of preventive therapy among silicotics. However, the populations studied tend to be rather small and important details concerning study design are often lacking in these reports. In a nonrandomized retrospective analysis, Burilkov23 compared the incidence of tuberculosis among 825 silicotics who were treated with INH for varying periods of 1-18 months to the incidence of tuberculosis among a group of 2,408 silicotics left untreated. The average annual incidence of tuberculosis over a three-year follow-up period among those treated was 0.32 per cent. Among those left untreated the average annual incidence was 2.66 per cent. Konaleva, et al.,24 report reducing tuberculosis 9.7 fold in a group of 397 silicotics treated with INH of two months duration twice yearly who were compared to a group of 317 untreated controls. Apparently on the basis of these reports the use of repetitive, intermittent short pulses of INH has become a rather standard form of preventive therapy for silicotic patients in several European countries.21'22 The use of a standard 12-month course of INH (300 mg daily) in the Ottawa County project was based on published ATS recommendations5 and the results of an unpublished U.S. Public Health Service randomized, controlled preventive therapy trial conducted in Wilkes-Barre, Pennsylvania. In that trial, 400 persons with anthracosilicosis and . 5 mm reactions to PPD-S were randomly assigned to a regimen of INH or placebo for one year. After a five-year follow-up there was a 50 per cent reduction in tuberculosis cases among the INH-treated group as compared to the untreated controls. The participants in Wilkes-Barre were suffering from mixed dust pneumoconiosis; thus, the results may not AJPH April 1979, Vol. 69, No. 4
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SCREENING
cn cn C.)
CZ
U-
z
5
YR.
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FIGURE 4-Total Number of New Active TB Cases Ottawa County 196-1977
be directly transferable to the treatment of persons with pure silicosis, such as those in Ottawa County. Other reports of INH preventive therapy among silicotics have been discouraging, e.g., the results of Berard, et al,25 and Jindrichova.26 However, many of the participants in Berard's study had signs and/or symptoms suggestive of active disease and, in retrospect, should not have been treated with a single drug. (Our case #1 [see Appendix] illustrates the failure of single drug therapy which can be expected when there is radiographic evidence of progressive disease although sputum cultures may remain negative.) Jindrichova26 studied the efficacy of INH 5 mg/Kg/day given for two years among a small group of patients in Eastern Bohemia and was unable to demonstrate a protective effect. In summary, the evidence that INH preventive therapy is effective in preventing tuberculosis among silicotics is not clear-cut, due in part to the absence of any large controlled trials. Some studies do suggest that INH can give some degree of protection to silicotics infected with M. tuberculosis but the degree of protection offered may be less than the protection INH preventive therapy affords in other situations such as in the treatment of household contacts.27 Although it is still too early to know what impact the use AJPH April 1979, Vol. 69, No. 4
of INH preventive therapy among silicotics in Ottawa County will have on future tuberculosis morbidity, the fact that three patients with silicosis who took isoniazid for 6, 10, and 12 months subsequently developed bacteriologically proven tuberculosis is disappointing. However, one of the patients may hav§ taken his medication very irregularly (case #1, Appendix) and one may have been infected initially with drug resistant organisms (case #2, Appendix). The disappointing results of preventive therapy among silicosis patients reported above has its corollary in reports concerning the treatment of tuberculous disease among these patients. Since the 1950s numerous reports28-37 have appeared which indicate that tuberculosis among pneumoconiosis victims responds much less satisfactorily to standard chemotherapy than tuberculosis among those without this complication. Fortunately, the introduction of rifampin seems to have improved the results of treatment of tuberculosis among pneumoconiosis victims.38 The use of rifampin in this project perhaps accounts for our success in achieving sputum negativity among the cases found during this project. (All but one of our 12 patients were treated with regimens containing rifampin.) We suggest that multiple drug therapy (including INH and rifampin) is justified for all silicosis patients who have clinical signs, particularly radiographic changes, compatible with progressive tuberculosis regardless of the results of bacteriologic examinations. Our experience with preventive therapy in the Ottawa County project was also disappointing in regard to the frequency of adverse reactions attributed to INH. Seven out of 50 persons in the target group with abnormal X-rays discontinued the drug because of adverse reactions. However, only one was suspected of having INH-induced hepatitis. In a previous U.S. Public Health Service study, a tendency of older patients to discontinue INH because of gastrointestinal and constitutional symptoms was noted, although the frequency with which this occurred was lower than in the current study.39 It may also be that the concomitant presence of silicosis made our patients more susceptible to or less tolerant of these side effects. The frequency of silicotuberculosis in the United States at the present time is unknown, but silica exposure and the risk of silicosis and silicotuberculosis continues for a large number of workers.40 The physician who diagnoses silicosis or silicotuberculosis in one of his patients should consider the public health implications of this finding. The identification of such a patient may indicate that there is a community health problem, e.g., a previously unknown reservoir of silicosis cases may exist and/or occupational exposure to silica dust may be continuing. Therefore, the opportunity for prevention of further death and disability due to silicosis and silicotuberculosis may be missed if one fails to consider these aspects of the problem. The results of the Ottawa County project demonstrate that useful selective tuberculosis screening programs can be designed using information available from the tuberculosis case register. The initial selective approach to the problem which we originally proposed, i.e., identification and screening of those in the target group, was highly successful. Extending screening beyond the target group may have im345
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proved participation among those in the target group but increased the cost and effort disproportionately to the yield.
Appendix Cases of tuberculosis which occurred among persons who participated in the project are summarized below: Case #1-A white male, age 81, with a 6-year history of underground mining. In 1960 he was found to have linear fibrosis of both upper lobes on a chest X-ray. A chest X-ray taken in 1971 again showed the apical fibrosis but, in addition, perihilar fibrosis and calcification was noted. Isoniazid (INH) 300 mg daily was begun but discontinued after 11/2 months because of gastrointestinal intolerance and a rash. In February 1975 he was started on daily triple drug therapy (INH 300 mg, ethambutol [EMBI 1200 mg, and rifampin [RIF] 600 mg) because of increasing fibrosis in the mid and lower lung fields bilaterally, nodular densities in the left lower lung field, and pleural scamng. RIF and EMS3 were discontinued after two months when all culture results were reported as negative. After six months he discontinued taking INH because of nausea. In April 1976 he developed a productive cough and anorexia. A sputum culture was positive for M. tuberculosis which was sensitive to all drugs. He was treated with INH 300 mg daily and RIF 600 mg daily. His sputum converted to negative within four months and he continues to do well. Case #2-A white male, age 61, with a 35-year history of underground mining. An intermediate strength PPD given on 10/28/74 was read as 12 mm. A chest X-ray taken three days later revealed nodular densities throughout both lung fields most extensive in the upper lobes. Sputum cultures for mycobacteria were negative. He was diagnosed as having silicosis. INH 300 mg daily was prescribed and was apparently taken faithfully for 12 months. Approximately one year later the patient complained of increasing dyspnea and productive cough following a "swine flu" vaccination. Sputum cultures were positive for M. tuberculosis resistant to 1.0 ,ug/ml of INH. He was treated with RIF 600 mg daily and EMB 1200 mg daily and has responded well. Case #3-A white male, age 66, with a 27-year history of underground mining. This patient had radiographic evidence of silicosis in 1958 but had never received preventive therapy. In March 1975 he was started on INH 300 mg daily. He apparently took INH regularly for 10 months before discontinuing it. Approximately 15 months after he stopped taking INH, he began to have increasing dyspnea and sputum production. The chest X-ray was unchanged but a sputum culture was positive for M. tuberculosis, sensitive to all drugs. He was begun on RIF 600 mg daily and EMB 1600 mg daily and has responded well. Case #4-A white male, age 79, with a 12-year history of mining. In March 1975 this patient had a 10 mm tuberculin reaction. A chest X-ray showed small irregular nodular densities throughout both lung fields which were conglomerate in the right perihilar region and right base. Preventive therapy was recommended but the patient refused. Fifteen months later he developed a productive cotigh, dyspnea, and tightness in the chest. These symptoms persisted for seven months before he was hospitalized for "pneumonia." In January 1977 sputum specimens were positive for M. tuberculosis. He began INH 300 mg daily and EMB 1000 mg daily which he took for three months before having prostate surgery. At that time his antituberculosis drugs were discontinued for some unknown reasons. Treatment was resumed within a month but his sputum cultures remain positive.
REFERENCES 1. 1976 Tuberculosis Statistics, Center for Disease Control, Atlanta, Ga. 1977 DHEW Publication No. (CDC 77-8249).
2. American Lung Association/American Thoracic Society. Diagnostic Standards and Classification of Tuberculosis and Other Mycobacterial Diseases, American Lung Association, New York, 1974. 346
3. Vestal AL: Procedures for the Isolation and Identification of Mycobacteria, DHEW Publication No. CDC 76-8230, 1975. 4. Bohlig H, Bristol LJ, Cartier PH, et al: UICC/Cincinnati Classification of the Radiographic Appearances of Pneumoconioses, Chest 58:57-67, 1970. 5. American Thoracic Society. Preventive Therapy of Tuberculous Infection. Am Rev Resp Dis 110:371-374, 1974. 6. Agricola G: De re Metallica (1556) Book I. translated from first edition of 1556 by H. C. Hoover and L. Hoover, San Francisco: Mining and Science Press, 1912, 12 vol. 7. Watkins-Pitchford W and Moir J: South African Institute for Medical Research, Report No. 8, 1916. 8. Lanza AJ, and Vane RJ: The prevalence of silicosis in the general population and its effects upon the incidence of tuberculosis. Am Rev Tuberc 29:8-16, 1934. 9. Riddell AR: The clinical aspects of simple silicosis and silicosis with tuberculosis. Am Rev Tuberc 29:36-42, 1934. 10. Gardner LU: Silicosis and its relationship to tuberculosis. Am Rev Tuberc 29:1-7, 1934. 11. Gooding CG: Pneumoconiosis in South Wales anthracite miners. Lancet 2:891-896, 1946. 12. Theodos PA, and Gordon B: Tuberculosis in Anthracosilicosis. Am Rev Tuberc 65:24-47, 1952. 13. Trasko VM: Some facts on the prevalence of silicosis in the United States. Arch Indust Health 14:379-386, 1956. 14. Cathcart RT, Theodos PA, and Fraimow W: Anthracosilicosis. Arch Intern Med 106:368-377, 1960. 15. Flinn RH, Bruton HP, Doyle HN, et al: Silicosis in the Metal Mining Industry. Public Health Service Publication No. 1076, U.S. Department of Interior, Bureau of Mines, U.S. Government Printing Office, Washington, DC, 1963. 16. Paul R: Silicosis in Northern Rhodesia copper mines. Arch Environ Health 2:96-109, 1961. 17. Chatgidakis CB: Silicosis in South African white gold miners. Medical Proceedings 9:383-392, 1963. 18. Monaco A: Antituberculous chemoprophylaxis in silicotics. Bull. Int. Union Against Tuberculosis 35:51-6, 1964. 19. Capezzuto A: Analisi Statistica Sull'Evoluzione Della Silicosi Polmonare. Considerazioni Sui 1,370 Casi Di Oltre Un Ventennio, Folia Medica (Napoli) 52:23-37, 1969. 20. Bruce T: Silicotuberculosis, Scand. J. Resp. Dis. Suppl. 65:139146, 1968. 21. Burckhardt P: Die Silikotuberkulose und ihre Prophylaxe, Schweiz. Med. Wochenschr 97:980-982, 1967. 22. Barras G: Silico-tuberculose en Suisse, Schweiz Med. Wochenschr. 100:1802-1808, 1910. 23. Burilkov T: Tuberkulosevorbeugung bei Silikose, Zeitschrift fur die Gesamte Hygiene Grenzgebetiete (Berlin) 15:744-50, 1969. 24. Konaleva SI, Levchishina GI, and Turdiev AT: Experience with Chemoprophylaxis of Tuberculosis in Silicotic Patients, Problemy Tuberkuleza (Moskva) 47:10-12, 1969. 25. Berard J, Ode L, Moulin J, and Guediche M: Chimio-prophylaxie de la Complication Tuberculeuse chez le Silicotique. Poumon et le Coeur. 28:97-100, 1972. 26. Jindrichova J: Der Einfluss der Praventiven Verabreichung von INH auf die Entstehung der Tbc-Komplikationen bei den Silikose-Kranken Pneumonologie (Berlin) 148:245-256, 1973. 27. Ferebee SH: Controlled chemoprophylaxis trials in tuberculosis: A general review. Adv Tuberc Res 17:28-106, 1969. 28. Prignot J: La Tuberculose des Houilleurs, Arscia Ed., Brussels, 1959. 29. Ramsay JH and Pines A: Results of treatment of pneumoconiosis complicated by tuberculosis. Brit Med J 2:345-348, 1959. 30. Morrow CS: The results of chemotherapy in silicotuberculosis. Am Rev Resp Dis 82:831-834, 1960. 31. Balmes A, Cazamian P, Pternitis C, et al: Le Traitement de la Complication Tuberculeuse de la Silicose du Houiller par les Associations D'antibiotiques, Poumon et le Coeur 5:431-437,
1960. 32. Gernez-Rieux C, Balgairies E, Voisin C, and Fournier P: Pneumoconio-tuberculosis. Results of medical and combined medical surgical therapy. Am Rev Resp Dis 82:835-842, 1960. AJPH April 1979, Vol. 69, No. 4
TBc SCREENING PROJECT IN MINING COMMUNITY 33. Prignot J and Godin H: Resultats Eloignes du Traitement de la Tuberculose de Houillers. Arch Mal Prof 23:125-131, 1%2. 34. Ramsey JHR and Pines A: The late results of chemotherapy in pneumoconiosis complicated by tuberculosis. Tubercle 44:476479, 1%3. 35. Gyselen A, Prignot J, Cosemans J, and Verbist L: Experience Sanatoriale des Tuberculostatiques de Relais. Lille Med. 8:1151- , 1%3. 36. Medical Research Council/Miners' Chest Diseases Treatment Centre: Chemotherapy of Pulmonary Tuberculosis with Pneumoconiosis. Tubercle. Lond. 44:47-70, 1%3. 37. Medical Research Council/Miners' Chest Diseases Treatment Centre: Chemotherapy of Pulmonary Tuberculosis with Pneumoconiosis, Tubercle 48:1-10, 1967. 38. Dubois P, Gyselen A, and Prignot J: Rifampin-combined chemotherapy in coal-worker's pneumoconio-tuberculosis. Am Rev Resp Dis 115:221-228, 1977.
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39. KopanoffDE, Snider DE, and Caras GJ: Isoniazid-related hepatitis-A U.S. Public Health Service cooperative surveillance study. Am Rev Resp Dis 117:991-1001, 1978. 40. Ziskind M, Jones RN, and Weill H: Silicosis. Am Rev Resp Dis 113:643-665, 1976.
ACKNOWLEDGMENTS This project was supported by Contract No. 21-74-541 from the Tuberculosis Control Division, Bureau of State Services, Center for Disease Control, Atlanta, GA. The authors appreciate the excellent and untiring efforts of the project staff: Jean Walser, RN, Margaret Layton, Charlene Dixon, and Billie Deibel. Special thanks are also due Gloria Ingram, RN, and other members of the Ottawa County Health Department. Finally our thanks to the many persons at the Oklahoma State Department of Health and the Center for Disease Control who assisted us.
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Abstract: Following a retrospective review of tuberculosis cases reported from Ottawa County, Oklahoma, from 1969 through 1973, a selective tuberculosis screening project was implemented. Screening of a "target group" of the population, 519 former miners, -50 years of age, resulted in the discovery of abnormal chest X-rays in 182; (103 with silicosis, 36 with silicotuberculosis, 12 with inactive tuberculosis, and 31 with other abnormalities). Eighty-five of these persons had positive tuberculin skin tests. Preventive therapy was recommended for 50, and 36 completed the prescribed course of treatment. Eight new bacteriologically confirmed cases of tuberculosis were found and treated.
A large number of persons (1,904) residing in the same area who were not part of the target group were also screened for tuberculosis. This group contained a large number of positive tuberculin reactors but very few were candidates for isoniazid preventive therapy. Thirteen persons in this group had abnormal chest Xrays consistent with inactive tuberculosis but 12 had been identified and given preventive therapy before the project began. These data suggest that selective approaches to screening for tuberculosis in a community which are based on an in-depth retrospective review of the tuberculosis case register can be highly successful. (Am. J. Public Health 69:340-347, 1979.)
Tuberculosis persists as a significant public health problem as evidenced by the fact that over 30,000 new cases were reported in the United States during 1976.1 Because of the declining incidence of tuberculosis, however, efficient tuberculosis control programs today no longer utilize the mass campaigns of the past aimed at screening large portions of the population. Since tuberculosis cases are not evenly distributed throughout the population, methods for identifying subgroups of the population which are at high risk of developing tuberculosis must be found so that the individuals in these groups can be screened for the presence of tuberculosis and/or tuberculous infection and given appropriate therapy. Analysis of the information collected for several years by the Tuberculosis and Respiratory Disease Division, Oklahoma State Department of Health, concerning tuberculosis
cases occurring in Ottawa County, Oklahoma, suggested that this County contained a subpopulation at high risk of developing tuberculosis. The data further suggested that a significant contribution toward reducing mortality and morbidity from tuberculosis could be made by conducting a selective tuberculosis screening project in the County. The development, implementation, conduct, and results of this project are the subject of this report.
From the Tuberculosis and Respiratory Disease Division, Oklahoma State Department of Health, Oklahoma City. Dr. Snider is presently with the Tuberculosis Control Division, Bureau of State Services, CDC. Address reprint requests to Technical Information Services, Bureau of State Services, Center for Disease Control, Atlanta, GA 30333. This paper, submitted to the Journal March 7, 1978, was revised and accepted for publication July 6, 1978. 340
Materials and Methods Background The Tuberculosis and Respiratory Disease Division, Oklahoma State Department of Health, was aware of the high incidence of tuberculosis in Ottawa County for many years (Figure 1). The Division knew that many of the cases of tuberculosis diagnosed in Ottawa County had coexisting silicosis. This was not surprising since this area was part of the so-called Tri-State Mining District where extensive lead and zinc mining operations were conducted during the first half of the century. Although mining operations had been discontinued, the Division assumed that a number of the curAJPH April 1979, Vol. 69, No. 4
TBc SCREENING PROJECT IN MINING COMMUNITY 500
more striking when their average annual new active case rates were compared. Using the 1970 census population as the base population upon which to calculate rates, the "Picher Area" was found to have an average annual new case rate of 98.1 per 100,000 population; a rate nearly three times that of the County as a whole.
480
° 0.
380 360
0 a.
340
o -
320 300
I--
1280
260 240 220
200
180
OTTAWA
160 140 120
100 80 60 40
OKLAHOMA
20
1945
1950
1955
1955
1960
1970
1915
YEAR
FIGURE 1-New Active TB Case Rates-Ottawa County and State of Oklahoma 1944-1975
rent residents of Ottawa County were former miners, some of whom had silicosis. In order to gather more information about the tuberculosis problem in Ottawa County, the Tuberculosis Case Register at the State Department of Health was searched for all new active* tuberculosis cases reported in the County between January 1, 1969, and January 1, 1974. A total of 51 new active cases of tuberculosis were found. Thirty-six (70.6 per cent) of the 51 patients resided in the "Picher Area"-an area where extensive "hard-rock" mining occurred previously. Thirty-one of these 36 persons were 2 50 years of age; 29 were male and 7 were female. Twenty (39 per cent) of the 51 cases had silicotuberculosis and 17 of these 20 resided in the Picher Area. All 17 were males, 15 of whom were 2 50 years of age. The differences in the incidence of tuberculosis among the various communities in Ottawa County became even *At the time of this study recent changes in the diagnostic standards and classification of tuberculosis2 had not been implemented. Therefore, the terms "active" and "inactive" were used to classify these patients.
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Project Design, Implementation, and Conduct In view of these findings, we felt that a selective rather than a mass tuberculosis screening project, in the Picher Area, would be the most efficient approach to reducing tuberculosis morbidity in the County. The target group initially selected for screening were males 50 years of age and over who lived in the Picher Area and who had a history of having worked in the mining industry. However, from discussions with residents of the area, it became apparent that the project could not be limited to this target group. A few of the former miners were known to have moved into another part of the County, particularly the City of Miami. Therefore, former miners residing anywhere in the County were invited through newspaper articles, radio spots, posters, etc., to participate in the project. There was also a great deal of local concern that the project might stigmatize the target group unless a broader base of support were generated. Accordingly, emphasis was placed on the tuberculosis problem in the whole Picher community, and arrangements were made for two community workers to conduct a house-to-house canvass of the entire Picher Area. Their responsibilities included obtaining medical histories relevant to tuberculosis and silicosis, and administering tuberculin skin tests to persons in the target group and others interested in participating in the screening program. All skin tests were administered on the volar surface of the forearm with 5 TU of Tween-stabilized, PPD-T using the Mantoux technique. All skin tests were read by project staff members 48-96 hours after administration. Only the transverse diameter of induration was read and recorded. Induration of 10 mm or more was considered positive. All men received a posterior-anterior chest X-ray regardless of the tuberculin skin test results, while only those women whose skin tests were read as 10 mm or greater were X-rayed. Two sputum specimens for smear and culture were obtained from all patients who gave a history of a chronic productive cough (> 2 weeks duration) and from all persons with radiographic findings compatible with tuberculosis and/ or silicosis. If necessary, sputum production was induced with ultrasonic aerosol nebulizer using isotonic saline solution. Specimens were processed by the Bureau of Laboratories, Oklahoma State Department of Health, according to established procedures.3 X-rays were reviewed by the staff physician in charge of the project. The diagnosis of silicosis was based on the typical radiographic findings of pneumoconiosis4 in patients who gave a history of having worked in a dusty mining environment for a minimum of three years. The diagnosis of active tuberculosis was based on the finding of at least one positive culture for M. tuberculosis from patients with clinical and/or radiographic evidence of progressive disease. The diagnosis of inactive tuberculosis 341
BURKE, ET AL.
was based either on a documented history of culture-proven tuberculosis or on the finding of a positive tuberculin skin test in patients with negative cultures who had radiographic changes compatible with nonprogressive tuberculosis and/or silicotuberculosis. In the absence of a documented past history of culture-proven tuberculosis, only those silicotic patients with positive skin tests who had extensive upper lobe involvement were classified as having inactive silicotuberculosis. Thus, the frequency of inactive tuberculosis in this population may have been somewhat underestimated.
Results During the canvassing process, the community workers identified 519 persons in the target group, i.e., males 50 years of age or over with a mining history who lived in the Picher area. Figure 2 shows the results of attempts to screen this target group. A total of 367 persons in the target group (71 per cent) participated in the project (93 of the 152 persons who did not participate had already received adequate treatment or had been examined for tuberculosis during the previous two years). Thus, only 59 persons (11 per cent) in the target group of 519 who "should have been" screened refused to participate. Ninety per cent of those in the target group who participated in the project were initially screened by chest X-ray. Fifty-five per cent of these persons had abnormal X-rays, most of them compatible with silicosis and/or tuberculosis. Of the 182 persons with abnormal chest X-rays, 81 per cent received a tuberculin skin test. Thirty-one of the 34 persons not skin tested had a history of a positive test usually associated with a history of tuberculosis; two had recently had a negative tuberculin test; and one refused skin testing. Eighty-five (57 per cent) of the 148 persons with abnormal X-rays had positive skin tests and preventive therapy with isoniazid (300 mg daily for one year) was prescribed for 50 who had abnormal X-rays compatible with silicosis and/or inactive tuberculosis.** Thirty-six (72 per cent) of the 50 persons placed on INH completed the prescribed course of therapy while 14 (28 per cent) prematurely discontinued (see Figure 2). The incidence of adverse reactions resulting in discontinuance of therapy was high in this older age group (7 out of 50 or 14 per cent). However, only one patient was withdrawn from the study because of suspected INH-related hepatitis. Most patients discontinued therapy after experiencing less serious adverse reactions such as headache, fatigue, anorexia, nausea, vomiting, dizziness, rash, chills, and malaise.*** **In the judgment of the staff physician, preventive therapy was contraindicated in 27 persons because of their age (> 35 years old) and because none had X-ray abnormalities suggestive of silicosis and/or tuberculosis (see reference 5). Preventive therapy was contraindicated in eight because of the presence of active disease. ***A relationship between isoniazid administration and these symptoms was suspected in all cases but was not proven by re-challenging with isoniazid. 342
A significant outcome of this screening project was the finding of eight new bacteriologically proven cases of tuberculosis. All of these patients had coexisting silicosis, all were white males, their mean age was 65 and the mean length of their mining experience was 28 years. All had been previously informed of an abnormality on their chest X-ray. Most had visited private physicians in recent years but the diagnosis of tuberculosis had not been made previously. From interviewing these eight new active cases of tuberculosis, 40 contacts were identified. Three of these contacts were 15 years of age or less. Fourteen contacts had positive tuberculin skin tests. Ten of these (including the three children) were placed on preventive treatment. Preventive therapy was felt to be contraindicated in four persons because of their advanced age and the belief that they had remote rather than recent infection. No new cases of tuberculosis were identified as a result of contact investigation. During the canvassing of the target area, the community workers obtained information on 1,904 other persons (in addition to the 519 persons identified in the target group) residing in the Picher area. The results of screening activities among this group is shown in Figure 3. Of the 1,904 persons who gave information to the canvassers, 1,203 (63 per cent) were skin tested. Of those skin tested, 25 per cent had positive reactions. All persons with positive reactions were X-rayed and five cases of silicosis and six cases of inactive tuberculosis were identified. Four of the five silicosis cases were recommended for preventive treatment. Two of these persons died of unrelated illnesses before completing preventive therapy and two discontinued it due to adverse reactions. Of the six inactive tuberculosis cases, five had received preventive therapy before the project began and one completed therapy during the project. Among those who were not skin tested, seven cases of inactive tuberculosis were identified. However, all seven had received treatment prior to the beginning of the project. The number of new active cases of tuberculosis reported in Ottawa County each year from 1969 through 1977 is shown in Figure 4. During calendar year 1976 (the year the project was completed), only five new cases of tuberculosis were reported (including two cases of silicotuberculosis). This was the smallest annual number of cases ever reported in the County. During 1977, however, there were 11 new tuberculosis cases in the County, two with co-existing silicosis. Thus, since the termination of the project a total of 16 new tuberculosis cases have been reported from Ottawa County. Four of these cases are of particular interest because they occurred among persons in the target group who participated in the project. A brief resume of each of these patients is given in the Appendix.
Discussion The decision to conduct this tuberculosis screening project in a community of former miners was based on three assumptions: 1) that a large proportion of these miners would be found to have silicosis; 2) that the prevalence of AJPH April 1979, Vol. 69, No. 4
TBc SCREENING PROJECT IN MINING COMMUNITY
FIGURE 2 -Ottawa County Project-Results of Screening among the "Target Group"
tuberculosis is unusually high among miners or former miners with silicosis; and 3) that the incidence of tuberculosis in this population could be substantially reduced by giving isoniazid preventive therapy (300 mg daily for 12 months) to positive tuberculin reactors with abnormal chest X-rays compatible with silicosis and/or inactive silicotuberculosis. The results of our screening activities among the target group of 519 former miners confirm that our first assumption was correct. Of the 330 former miners in the target group who received a chest X-ray, 139 (42 per cent) showed evidence of silicosis or silicotuberculosis. The literature is replete with references in support of our second assumption, i.e., that there is an increased frequency of tuberculosis among persons with silicosis6-20. In AJPH April 1979, Vol. 69, No. 4
our target group, eight new cases of tuberculosis (all with coexisting silicosis) were discovered among 367 persons screened in a two-year interval. This represents a new case rate qf 1,090 per 100,000 persons screened per year. In contrast, the case rate for the entiie County was 34 per 100,000 per year between 1969 and 1974. Thus, the results of the project also confirmed the fact that tuberculosis and silicosis are frequently coexistent. The frequency with which tuberculosis occurs among silicosis patients may vary depending upon: 1) the prevalence of tuberculous infection in the population; 2) the prevalence of tuberculosis in the surrounding population; 3) the stage and type of silicosis; 4) the age and general health of the population (e.g., nutritional status, presence of other 343
BURKE, ET AL.
FIGURE 3-Ottawa County Project-Screening of Persons Outside the "Target Group"
medical conditions); 5) the preventive measures applied; and 6) the diagnostic methods used and the intensity with which they are applied. The prevalence of infection in the entire Ottawa County target group is unknown since skin tests were generally performed only if the participant's chest X-ray was abnormal. Fifty-seven per cent of those with abnormal X-rays who were skin tested had a tuberculin reaction of 10 mm or more indicating that a significant reservoir of tuberculous infection exists in the population. The prevalence of infection among persons in the surrounding population (those outside the target group) was much lower; 303 of 1,203 persons skin tested (25 per cent) had positive reactions. These data suggest that most of the tuberculosis occurring in this population resulted from reactivation of a remote, latent infection in a member of the target group rather than from exogenous
re-infection. The prevalence of tuberculosis among former miners in Ottawa County may be particularly high because many are suffering from the more advanced stages of "pure" silicosis. Bruce has shown that the prevalence of complicating tuberculosis is higher among persons with the more advanced stages of silicosis.20 He also concluded that tuberculosis is more common among persons with "pure" silicosis than among those with mixed-dust pneumoconiosis. This population of former miners would also be expected to be at higher risk of tuberculosis because of their advanced age and an associated increase in the number of concomitant medical conditions. Tuberculosis could have been prevented in this population in a variety of ways. Of obvious importance in this regard is the prevention of the silicotic process itself. This can 344
be accomplished by: wetting down mine shafts to prevent the generation of dusts, requiring workers exposed to silica dust to wear effective masks or hoods, instituting effective ventilation, and limiting the amount of time individual workers are exposed to dust. In the past, BCG vaccination of tuberculin-negative silicotics was also recommended, but current opinion21-23 favors the notion that BCG vaccination of silicotics is contraindicated. Among silicotics with positive tuberculin tests, BCG vaccination would be expected to have no benefit. Therefore, the use of isoniazid preventive therapy in this group has been recommended.5 18, 21-24 In contrast to the extensive preventive therapy trials conducted among other groups (contacts, persons with fibrotic lesions, etc.), there are no large controlled trials of the use of INH preventive therapy among silicotics. We were able to find only one brief report concerning the efficacy of INH preventive therapy among silicotics in the English literature. Monaco"8 reported a trial among 811 silicotics with positive tuberculin reactions treated with INH and a group of 411 silicotics with positive reactions (not matched geographically) left untreated as controls. The INH (10 mg/Kg/day) was given for three months every six months for two years or longer. Over a five-year follow-up period, tuberculosis morbidity was 0.73 per cent among the treated group and 10.21 per cent among the controls. Thus, the treated group had a 14-fold reduction in new cases of tuberculosis. However, because this was not a randomized trial, these results must be interpreted with caution. The non-English literature contains several reports of preventive therapy among silicotics. However, the populations studied tend to be rather small and important details concerning study design are often lacking in these reports. In a nonrandomized retrospective analysis, Burilkov23 compared the incidence of tuberculosis among 825 silicotics who were treated with INH for varying periods of 1-18 months to the incidence of tuberculosis among a group of 2,408 silicotics left untreated. The average annual incidence of tuberculosis over a three-year follow-up period among those treated was 0.32 per cent. Among those left untreated the average annual incidence was 2.66 per cent. Konaleva, et al.,24 report reducing tuberculosis 9.7 fold in a group of 397 silicotics treated with INH of two months duration twice yearly who were compared to a group of 317 untreated controls. Apparently on the basis of these reports the use of repetitive, intermittent short pulses of INH has become a rather standard form of preventive therapy for silicotic patients in several European countries.21'22 The use of a standard 12-month course of INH (300 mg daily) in the Ottawa County project was based on published ATS recommendations5 and the results of an unpublished U.S. Public Health Service randomized, controlled preventive therapy trial conducted in Wilkes-Barre, Pennsylvania. In that trial, 400 persons with anthracosilicosis and . 5 mm reactions to PPD-S were randomly assigned to a regimen of INH or placebo for one year. After a five-year follow-up there was a 50 per cent reduction in tuberculosis cases among the INH-treated group as compared to the untreated controls. The participants in Wilkes-Barre were suffering from mixed dust pneumoconiosis; thus, the results may not AJPH April 1979, Vol. 69, No. 4
TBc SCREENING PROJECT IN MINING COMMUNITY
SCREENING
cn cn C.)
CZ
U-
z
5
YR.
TB
SILICO,TB
FIGURE 4-Total Number of New Active TB Cases Ottawa County 196-1977
be directly transferable to the treatment of persons with pure silicosis, such as those in Ottawa County. Other reports of INH preventive therapy among silicotics have been discouraging, e.g., the results of Berard, et al,25 and Jindrichova.26 However, many of the participants in Berard's study had signs and/or symptoms suggestive of active disease and, in retrospect, should not have been treated with a single drug. (Our case #1 [see Appendix] illustrates the failure of single drug therapy which can be expected when there is radiographic evidence of progressive disease although sputum cultures may remain negative.) Jindrichova26 studied the efficacy of INH 5 mg/Kg/day given for two years among a small group of patients in Eastern Bohemia and was unable to demonstrate a protective effect. In summary, the evidence that INH preventive therapy is effective in preventing tuberculosis among silicotics is not clear-cut, due in part to the absence of any large controlled trials. Some studies do suggest that INH can give some degree of protection to silicotics infected with M. tuberculosis but the degree of protection offered may be less than the protection INH preventive therapy affords in other situations such as in the treatment of household contacts.27 Although it is still too early to know what impact the use AJPH April 1979, Vol. 69, No. 4
of INH preventive therapy among silicotics in Ottawa County will have on future tuberculosis morbidity, the fact that three patients with silicosis who took isoniazid for 6, 10, and 12 months subsequently developed bacteriologically proven tuberculosis is disappointing. However, one of the patients may hav§ taken his medication very irregularly (case #1, Appendix) and one may have been infected initially with drug resistant organisms (case #2, Appendix). The disappointing results of preventive therapy among silicosis patients reported above has its corollary in reports concerning the treatment of tuberculous disease among these patients. Since the 1950s numerous reports28-37 have appeared which indicate that tuberculosis among pneumoconiosis victims responds much less satisfactorily to standard chemotherapy than tuberculosis among those without this complication. Fortunately, the introduction of rifampin seems to have improved the results of treatment of tuberculosis among pneumoconiosis victims.38 The use of rifampin in this project perhaps accounts for our success in achieving sputum negativity among the cases found during this project. (All but one of our 12 patients were treated with regimens containing rifampin.) We suggest that multiple drug therapy (including INH and rifampin) is justified for all silicosis patients who have clinical signs, particularly radiographic changes, compatible with progressive tuberculosis regardless of the results of bacteriologic examinations. Our experience with preventive therapy in the Ottawa County project was also disappointing in regard to the frequency of adverse reactions attributed to INH. Seven out of 50 persons in the target group with abnormal X-rays discontinued the drug because of adverse reactions. However, only one was suspected of having INH-induced hepatitis. In a previous U.S. Public Health Service study, a tendency of older patients to discontinue INH because of gastrointestinal and constitutional symptoms was noted, although the frequency with which this occurred was lower than in the current study.39 It may also be that the concomitant presence of silicosis made our patients more susceptible to or less tolerant of these side effects. The frequency of silicotuberculosis in the United States at the present time is unknown, but silica exposure and the risk of silicosis and silicotuberculosis continues for a large number of workers.40 The physician who diagnoses silicosis or silicotuberculosis in one of his patients should consider the public health implications of this finding. The identification of such a patient may indicate that there is a community health problem, e.g., a previously unknown reservoir of silicosis cases may exist and/or occupational exposure to silica dust may be continuing. Therefore, the opportunity for prevention of further death and disability due to silicosis and silicotuberculosis may be missed if one fails to consider these aspects of the problem. The results of the Ottawa County project demonstrate that useful selective tuberculosis screening programs can be designed using information available from the tuberculosis case register. The initial selective approach to the problem which we originally proposed, i.e., identification and screening of those in the target group, was highly successful. Extending screening beyond the target group may have im345
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proved participation among those in the target group but increased the cost and effort disproportionately to the yield.
Appendix Cases of tuberculosis which occurred among persons who participated in the project are summarized below: Case #1-A white male, age 81, with a 6-year history of underground mining. In 1960 he was found to have linear fibrosis of both upper lobes on a chest X-ray. A chest X-ray taken in 1971 again showed the apical fibrosis but, in addition, perihilar fibrosis and calcification was noted. Isoniazid (INH) 300 mg daily was begun but discontinued after 11/2 months because of gastrointestinal intolerance and a rash. In February 1975 he was started on daily triple drug therapy (INH 300 mg, ethambutol [EMBI 1200 mg, and rifampin [RIF] 600 mg) because of increasing fibrosis in the mid and lower lung fields bilaterally, nodular densities in the left lower lung field, and pleural scamng. RIF and EMS3 were discontinued after two months when all culture results were reported as negative. After six months he discontinued taking INH because of nausea. In April 1976 he developed a productive cough and anorexia. A sputum culture was positive for M. tuberculosis which was sensitive to all drugs. He was treated with INH 300 mg daily and RIF 600 mg daily. His sputum converted to negative within four months and he continues to do well. Case #2-A white male, age 61, with a 35-year history of underground mining. An intermediate strength PPD given on 10/28/74 was read as 12 mm. A chest X-ray taken three days later revealed nodular densities throughout both lung fields most extensive in the upper lobes. Sputum cultures for mycobacteria were negative. He was diagnosed as having silicosis. INH 300 mg daily was prescribed and was apparently taken faithfully for 12 months. Approximately one year later the patient complained of increasing dyspnea and productive cough following a "swine flu" vaccination. Sputum cultures were positive for M. tuberculosis resistant to 1.0 ,ug/ml of INH. He was treated with RIF 600 mg daily and EMB 1200 mg daily and has responded well. Case #3-A white male, age 66, with a 27-year history of underground mining. This patient had radiographic evidence of silicosis in 1958 but had never received preventive therapy. In March 1975 he was started on INH 300 mg daily. He apparently took INH regularly for 10 months before discontinuing it. Approximately 15 months after he stopped taking INH, he began to have increasing dyspnea and sputum production. The chest X-ray was unchanged but a sputum culture was positive for M. tuberculosis, sensitive to all drugs. He was begun on RIF 600 mg daily and EMB 1600 mg daily and has responded well. Case #4-A white male, age 79, with a 12-year history of mining. In March 1975 this patient had a 10 mm tuberculin reaction. A chest X-ray showed small irregular nodular densities throughout both lung fields which were conglomerate in the right perihilar region and right base. Preventive therapy was recommended but the patient refused. Fifteen months later he developed a productive cotigh, dyspnea, and tightness in the chest. These symptoms persisted for seven months before he was hospitalized for "pneumonia." In January 1977 sputum specimens were positive for M. tuberculosis. He began INH 300 mg daily and EMB 1000 mg daily which he took for three months before having prostate surgery. At that time his antituberculosis drugs were discontinued for some unknown reasons. Treatment was resumed within a month but his sputum cultures remain positive.
REFERENCES 1. 1976 Tuberculosis Statistics, Center for Disease Control, Atlanta, Ga. 1977 DHEW Publication No. (CDC 77-8249).
2. American Lung Association/American Thoracic Society. Diagnostic Standards and Classification of Tuberculosis and Other Mycobacterial Diseases, American Lung Association, New York, 1974. 346
3. Vestal AL: Procedures for the Isolation and Identification of Mycobacteria, DHEW Publication No. CDC 76-8230, 1975. 4. Bohlig H, Bristol LJ, Cartier PH, et al: UICC/Cincinnati Classification of the Radiographic Appearances of Pneumoconioses, Chest 58:57-67, 1970. 5. American Thoracic Society. Preventive Therapy of Tuberculous Infection. Am Rev Resp Dis 110:371-374, 1974. 6. Agricola G: De re Metallica (1556) Book I. translated from first edition of 1556 by H. C. Hoover and L. Hoover, San Francisco: Mining and Science Press, 1912, 12 vol. 7. Watkins-Pitchford W and Moir J: South African Institute for Medical Research, Report No. 8, 1916. 8. Lanza AJ, and Vane RJ: The prevalence of silicosis in the general population and its effects upon the incidence of tuberculosis. Am Rev Tuberc 29:8-16, 1934. 9. Riddell AR: The clinical aspects of simple silicosis and silicosis with tuberculosis. Am Rev Tuberc 29:36-42, 1934. 10. Gardner LU: Silicosis and its relationship to tuberculosis. Am Rev Tuberc 29:1-7, 1934. 11. Gooding CG: Pneumoconiosis in South Wales anthracite miners. Lancet 2:891-896, 1946. 12. Theodos PA, and Gordon B: Tuberculosis in Anthracosilicosis. Am Rev Tuberc 65:24-47, 1952. 13. Trasko VM: Some facts on the prevalence of silicosis in the United States. Arch Indust Health 14:379-386, 1956. 14. Cathcart RT, Theodos PA, and Fraimow W: Anthracosilicosis. Arch Intern Med 106:368-377, 1960. 15. Flinn RH, Bruton HP, Doyle HN, et al: Silicosis in the Metal Mining Industry. Public Health Service Publication No. 1076, U.S. Department of Interior, Bureau of Mines, U.S. Government Printing Office, Washington, DC, 1963. 16. Paul R: Silicosis in Northern Rhodesia copper mines. Arch Environ Health 2:96-109, 1961. 17. Chatgidakis CB: Silicosis in South African white gold miners. Medical Proceedings 9:383-392, 1963. 18. Monaco A: Antituberculous chemoprophylaxis in silicotics. Bull. Int. Union Against Tuberculosis 35:51-6, 1964. 19. Capezzuto A: Analisi Statistica Sull'Evoluzione Della Silicosi Polmonare. Considerazioni Sui 1,370 Casi Di Oltre Un Ventennio, Folia Medica (Napoli) 52:23-37, 1969. 20. Bruce T: Silicotuberculosis, Scand. J. Resp. Dis. Suppl. 65:139146, 1968. 21. Burckhardt P: Die Silikotuberkulose und ihre Prophylaxe, Schweiz. Med. Wochenschr 97:980-982, 1967. 22. Barras G: Silico-tuberculose en Suisse, Schweiz Med. Wochenschr. 100:1802-1808, 1910. 23. Burilkov T: Tuberkulosevorbeugung bei Silikose, Zeitschrift fur die Gesamte Hygiene Grenzgebetiete (Berlin) 15:744-50, 1969. 24. Konaleva SI, Levchishina GI, and Turdiev AT: Experience with Chemoprophylaxis of Tuberculosis in Silicotic Patients, Problemy Tuberkuleza (Moskva) 47:10-12, 1969. 25. Berard J, Ode L, Moulin J, and Guediche M: Chimio-prophylaxie de la Complication Tuberculeuse chez le Silicotique. Poumon et le Coeur. 28:97-100, 1972. 26. Jindrichova J: Der Einfluss der Praventiven Verabreichung von INH auf die Entstehung der Tbc-Komplikationen bei den Silikose-Kranken Pneumonologie (Berlin) 148:245-256, 1973. 27. Ferebee SH: Controlled chemoprophylaxis trials in tuberculosis: A general review. Adv Tuberc Res 17:28-106, 1969. 28. Prignot J: La Tuberculose des Houilleurs, Arscia Ed., Brussels, 1959. 29. Ramsay JH and Pines A: Results of treatment of pneumoconiosis complicated by tuberculosis. Brit Med J 2:345-348, 1959. 30. Morrow CS: The results of chemotherapy in silicotuberculosis. Am Rev Resp Dis 82:831-834, 1960. 31. Balmes A, Cazamian P, Pternitis C, et al: Le Traitement de la Complication Tuberculeuse de la Silicose du Houiller par les Associations D'antibiotiques, Poumon et le Coeur 5:431-437,
1960. 32. Gernez-Rieux C, Balgairies E, Voisin C, and Fournier P: Pneumoconio-tuberculosis. Results of medical and combined medical surgical therapy. Am Rev Resp Dis 82:835-842, 1960. AJPH April 1979, Vol. 69, No. 4
TBc SCREENING PROJECT IN MINING COMMUNITY 33. Prignot J and Godin H: Resultats Eloignes du Traitement de la Tuberculose de Houillers. Arch Mal Prof 23:125-131, 1%2. 34. Ramsey JHR and Pines A: The late results of chemotherapy in pneumoconiosis complicated by tuberculosis. Tubercle 44:476479, 1%3. 35. Gyselen A, Prignot J, Cosemans J, and Verbist L: Experience Sanatoriale des Tuberculostatiques de Relais. Lille Med. 8:1151- , 1%3. 36. Medical Research Council/Miners' Chest Diseases Treatment Centre: Chemotherapy of Pulmonary Tuberculosis with Pneumoconiosis. Tubercle. Lond. 44:47-70, 1%3. 37. Medical Research Council/Miners' Chest Diseases Treatment Centre: Chemotherapy of Pulmonary Tuberculosis with Pneumoconiosis, Tubercle 48:1-10, 1967. 38. Dubois P, Gyselen A, and Prignot J: Rifampin-combined chemotherapy in coal-worker's pneumoconio-tuberculosis. Am Rev Resp Dis 115:221-228, 1977.
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39. KopanoffDE, Snider DE, and Caras GJ: Isoniazid-related hepatitis-A U.S. Public Health Service cooperative surveillance study. Am Rev Resp Dis 117:991-1001, 1978. 40. Ziskind M, Jones RN, and Weill H: Silicosis. Am Rev Resp Dis 113:643-665, 1976.
ACKNOWLEDGMENTS This project was supported by Contract No. 21-74-541 from the Tuberculosis Control Division, Bureau of State Services, Center for Disease Control, Atlanta, GA. The authors appreciate the excellent and untiring efforts of the project staff: Jean Walser, RN, Margaret Layton, Charlene Dixon, and Billie Deibel. Special thanks are also due Gloria Ingram, RN, and other members of the Ottawa County Health Department. Finally our thanks to the many persons at the Oklahoma State Department of Health and the Center for Disease Control who assisted us.
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