Public health issues of tuberculosis

Public Health Issues of Tuberculosis Jay B. Mehta, MD, and Asim K. Duff, MD ~

ransmission of tuberculosis (TB) is a paradox--at once extremely simple, yet extraordinarily complex. ''1 Tuberculosis is one of the most common infections in the world. It is estimated that i.5 billion p e o p l e - - a l m o s t one third of the world's popul a t i o n - a r e infected with the tubercle bacillus. Thus the human race makes up a large reservoir of infection which, acting as a slow "time bomb," continues to provide a steady number of new cases of active TB. Almost every new infection is the result of airborne transmission. Although a single inhaled tubercle bacillus can infect a susceptible host, TB is not considered "highly infectious" when compared to varicella, measles, and other diseases caused by airborne viruses. Here is the paradox. Although an unfortunate medical student or emergency room nurse may b e c o m e infected after brief contact with his/her first contagious case, scientific literature since the 1930s indicates that when TB was common and not effectively treated, it required an average of 6 to 8 months' exposure for conversion of skin tests of health care personnel in sanitoriums. ~ Perhaps this led to the mistaken belief that TB transmission requires prolonged exposure. Although we should discourage the health care worker's terror of catching the disease, we must dispel the old myth that TB is difficult to contract. The commonly held belief that tubercle bacilli dry out and die rather quickly once they are expelled from the human body is not true. Exhaled organisms are viable and infective for prolonged periods of time. 3 The situation of a susceptible host with human immunodeficiency virus (HIV) infection combined with the possibility of multidrug-resistant strains of TB poses a serious threat to health care workers as well as to persons living in highly endemic areas. Airborne transmission of TB occurs through droplet nuclei that may remain suspended in the air for several hours. The probability of transmission depends on (1) infectiousness of the source case, (2) environment in which exposure occurs, and (3) duration of exposure. The potential communicability of source-case infection depends on the bacterial load and number of droplet nuclei expelled by the infected per156

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Q-- Germ-Free Ventilation (cfm) FIG. 1. The effect of room ventilation on the probability of infection. 9 = Nardell; 9 = Catanzaro. (From Riley RL, Nardell EA. Controlling tuberculosis in health care facilities: ventilation, filtration, and ultraviolet air disinfection. In: Controlling Occupational Exposure to Tuberculosis, Plant Technology and Safety Management Series, Oakbrook Terrace, IL, Joint Commission of Accredition of Health Care Organizations, 1993.)

son. Cough frequency has been associated with infectiousness; so have certain procedures, including sputum induction, flexible bronchoscopy, and pentamidine aerosol treatments. In one study, 3 the half-life of aerosolized tubercle bacilli (H37Rv strain) was found to be about 6 hours. However, the concentration of bacilli is more dependent on dilution than viability. Ventilation with two room air exchanges per hour removes about 87% of airborne particles 3 (Fig. 1). Unlike the situation with fungal infection or Legionella, buildings are not reservoirs for tuberculous infection. Size of the droplet nuclei also plays an important role in infectiousness. Wells et al. 4 found 16 times as many tubercles in the lungs of rabbits breathing fine (2 pm) droplets as in those breathing large (12 to 15 ~tm) suspensions.4 The minimum infective dose for susceptible animals such as rabbits and guinea pigs was a single droplet nucleus containing one or a few bacilli. Because of their sensitivity, these animals make nearly ideal models with which to study the infectiousness of aerosolized droplet nuclei. DM, March 1997

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Control of Transmission Although adequate ventilation, air filtration, and ultraviolet light all have a place in controlling TB transmission, containment of the source is the most sensible first step in prevention. Prompt diagnosis of an infectious case and effective chemotherapy is by far the most desirable method of source control. Having the patient cover his face when coughing or sneezing is a simple mechanical method of controlling the spread of droplet nuclei. Effective chemotherapy reduces the cough, the bacterial load, and the risk of transmission. Although surgical face masks have been used for years, they lack both the "fit" and the filtration properties needed to provide adequate protection. Mouth- and nose-covering masks, so-called "personal respirators," have long been used in industry to protect workers from dust and fumes. Although such devices fit well and possess the ability to filter small droplet nuclei, they have their limitations. For instance, transmission may have already occurred before diagnosis of the index case. It is the unknown case of active TB that is more likely to infect close contacts and occasionally health care workers. The National Institute of Occupational Safety and Health (NIOSH) has recommended various types of respirators, 5 some with replaceable filters, disposable masks, or both. Generally, these are available in three different sizes to assure proper fit. Powered air-purifying respirators employ a blower to pass contaminated air through a high-efficiency particulate air (HEPA) filter, which removes contamination and supplies purified air to a face piece, hood, or helmet. This type of respirator should be used when the risk of tuberculosis is especially high and disposable and reusable face masks do not provide adequate protection2 Although isolation is recommended for all recently diagnosed cases, it is hard to ascertain at precisely what point during administration of antituberculosis therapy the patient's disease becomes noncommunicable. The current theory that 2 to 3 weeks of antituberculosis therapy invariably renders the patient noncontagious is a misconception. 6 Even in a hospital setting, sputum smear/culture status is still an important factor in determining whether isolation of the patient is necessary. Isolation rooms must have negative pressure and a sufficient number of air exchanges (3 to 5 per hour) to clear the room of floating droplet nuclei. 3,6Air from isolation rooms should be vented to the outdoors or disinfected before being recirculated. HEPA filters are very useful inTB clinics and other facilities where cough-inducing procedures are carried out. These filters remove 99% of the airborne particles more than 0.3 mm in diam158

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Time (minutu) Fig. 9. The effect of ultraviolet irradiation on aerosolized bacilli. Disappearance of aerosolized bacille Calmette-Gu~rin (BCG) from room air with and without upper air ultraviolet (UV) irradiation using one suspended fixture with a 17-watt tube. AC/h = Air changes per hour. 9 = UV off: 2 AC/hr (12/21/74); 9 = 17 W UV: 12 AC/hr (12/21/74). (From Riley RL, Nardell EA. Controlling tuberculosis in health-care facilities: ventilation, filtration, and ultraviolet air disinfection. In: Controlling Occupational Exposure to Tuberculosis, Plant Technology and Safety Management Series, Oakbrook Terrace, IL, Joint Commission of Accreditation of Health Care Organizations, 1993.)

eter. 6 Unfortunately, such machines have high flow resistance and greater energy requirements to move air through the filter, rendering them expensive and noisy. They also need periodic checks to exclude leakage around the filter. Ultraviolet germicidal irradiation (UVGI) is another effective method of killing mycobacteria (Fig. 2). On the basis of experiments with bacille Calmette-Gu6rin (BCG) vaccine, it is recommended that a 30-watt ultraviolet fixture be used for each 200 square feet of floor area. 7,8 Ultraviolet fixtures must be designed to prevent excessive exposure to radiation, either direct or reflected. Overexposure is known to cause irritation to the skin and eyes. For safety, NIOSH recognizes an upper limit of 0.2 g W / c m 2 of continuous UVGI exposure over an 8-hour period. 9 Unfortunately, environmental control methods (masks, ventilation, filters, and UVGI) cannot guarantee total protection, particularly if an immunocompromised host encounters a highly infectious case. Hence control of TB ultimately depends on effective surveillance and prompt treatDM, March 1997

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ment. Strict adherence to national guidelines1~ will reduce the risk of transmission. Since these recommendations may be periodically updated, the reader is advised to consult the most recent local or federal guidelines before planning any major intervention.

Screening for Infection History of Exposure Active TB is a potential source of infection, regardless of whether the diagnosis has been established. Thorough investigation of all suspected cases, particularly those with a history of recent exposure, is therefore crucial. Traditionally, "contact investigation" is conducted by public health workers who tend to concentrate on close contacts. Accurate history taking and monitoring of positive skin test rate to assess the level of exposure among those tested is very important in determining whether to broaden the scope of the investigation. An average of 15% to 25% of the family members of active TB cases have positive skin test reactions.ll This is, of course, a higher percentage than that normally observed among the general population in the United States. If contact investigation continues to yield a high percentage of positivity (>15%), the "concentric circle" should be widened to include other contacts considered less likely to be infected from the index case. Children under the age of 2 years often display negative skin test results when tested within a few days of exposure. In one study, 12 it was shown that this group was commonly deprived of the opportunity for prevention. Current recommendations call for isoniazid (INH) preventive therapy in children in close contact with an active case, even if initial skin testing is negative. 13 Skin testing should be repeated 2 to 3 months later, at which point therapy can be discontinued if results are still negative. Appropriate history taking and clinical judgment should be used in conducting contact investigation and recommending preventive therapy.

Purified Protein Derivative Skin Testing Despite its limitations, purified protein derivative (PPD) skin testing remains a widely used method of identifying those infected with M. tuberculosis. Although many other tests have come and gone, PPD skin testing has maintained its popularity since 1930. Tuberculin. Tuberculin was first prepared by Robert Koch in 1890, approximately 8 years after he discovered the TB bacillus. His original claim that tuberculin was a treatment for TB proved to be false. In 189 t, Eber, a German veterinarian, tested cattle and found that 85% of 134 animals with 160

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positive skin reaction had tuberculous lesions at autopsy. 14 Eighty-nine percent of those that did not react to tuberculin had no such lesions. In the 1920s, nontuberculous mycobacteria were beginning to be recognized as a cause of false-positive skin test and smear findings. Mariette and Fenger 15 offered evidence that human beings exposed to nontuberculous mycobacteria tested positive when injected with higher concentrations of tuberculin prepared from M. tuberculosis. In 1953, Palmer ~6 skin tested 16,000 student nurses, demonstrating that while place of residence did not affect the percentage of positive reactions to five tuberculin units (TU), reactions to 250 TU were seen in a larger number of those living in southern states of the United States Cross-reactivity with nontuberculous mycobacteria and high prevalence of such mycobacteria in the soil and water account for the increased skin test response in southern areas of the country. Tuberculin has been administered in a variety of ways, such as cutaneous test (Von Pirquet), puncture test (Moro), conjunctival test (Calmette), and subcutaneous test (Koch). Over time, the intracutaneous test developed by Mantoux in 1908 became the most favored because of its precision and ability to quantitate the reaction (in millimeters of induration). In 1934 Seibert's preparation of PPD became a landmark in history. A single large lot of ammonia sulfate precipitated PPD (lot No. 49608) became the international standard that is today known as "PPD-S." The international unit dosage for PPD is defined as the biologic activity contained in 0.000028 mg of PPD-S. Immune Response. Soon after infection with the tubercle bacillus, Tlymphocytes in the regional lymph nodes proliferate, become sensitized, and begin circulating in the bloodstream within a few weeks. When a person is injected with tuberculin in the skin, the process stimulates the lymphocytes, ultimately resulting in a delayed type of hypersensitivity that requires 24 to 48 hours to appear. Dermal reactivity leads to vasodilation, edema, and the infiltration of lymphokines. After 48 hours, the area of induration--not the area of redness--is measured in millimeters. Erythema alone is insignificant and does not constitute a positive reaction. Blister formation, on the other hand, is considered significant. The adequate sensitization of the lymphocyte to produce a detectable delayed type of hypersensitivity reaction generally takes 2 to 10 weeks after a person is initially infected with M. tuberculosis This sensitivity may persist for years, although reactivity often wanes with increasing age. Many factors affect this response (Table 1). Mantoux Technique. This skin test involves the intracutaneous injection of 5 TU of tuberculin into the volar surface of the forearm. A tuberculin syringe with a 26- to 27-gauge needle is used to introduce 0.1 ml of DM, March 1997

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TABLE 1. Factors contributing to false-negative tuberculin reaction

Infections 9 Viral: Measles, chickenpox, m u m p s , HIV 9 Bacterial: Typhoid, overwhelming tuberculosis 9 Fungal: Blastomycosis Metabolic 9 Chronic renal disease Nutritional factors 9 Protein depletion Diseases affecting immunity 9 Hodgkin's disease, lymphoma, chronic lymphatic leukemia, chronic steroid therapy, sarcoidosis, renal failure Others 9 Atopic dermatitis, burns, live virus vaccination, advanced age Test method

9 Delayed injection after filling syringe 9 Subcutaneous injection 9 Error in reading or recording results Tuberculin reagent 9 Improper storage resulting in exposure to light 9 Contamination, improper dilution 9 Adsorption (prevented by Tween 80)

antigen just below the top layer of the skin. A discrete, pale elevation of the skin (wheal) 6 to 10 mm in diameter is generally produced. Tuberculin is adsorbed by glass and plastic. Therefore a detergent, Tween 80, is added by the manufacturer of tuberculin (PPD-T) to minimize its adsorption. Syringes should be filled with tuberculin antigen just before the skin test is given. Prolonged exposure to sunlight also reduces the potency of the antigen. Tuberculin containers should be sfored in refrigeration, but not frozen. Multiple-Puncture Test (MPT). The multiple-puncture test is commonly used for mass screening because of the speed and ease with which it can be administered. Tuberculin is introduced in the skin through prongs on the applicator device. A major limitation of the test is its lack of precision because the amount of tuberculin introduced in the skin cannot be controlled. While vesicular reactions to MPTs should be interpreted as positive, other reactions must be confirmed by Mantoux testing. Skin test resultsare normally read 48 to 72 hours after the test is administered. The margins of induration are found by drawing the index finger lightly across the reaction. After margins are marked, the area of induration is measured transversely at its widest diameter with a flexible ruler. Some readers prefer to use a ballpoint pen to outline the borders of induration. Results should be recorded in millimeters of induration rather than 162

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TABLE 2. Criteria for significant or "positive" tuberculin reaction ->5 mm induration is considered positive if: 9 Recent close contact to an active case 9 HIV-Jnfected 9 Abnormal chest radiograph suggestive of old tuberculosis >_10 mm induration is considered positive if: 9 Recent skin test converter 9 Foreign-born 9 High-risk group (low income population, alcohol abuse, IV drug abuse) 9 Medical risk factors (diabetes mellitus, immunosuppressive therapy, end-stage renal disease, extended corticosteroid therapy) 9 Residence in long-term care facility (nursing homes, prisons) _>15 mm is considered positive in all other persons

merely as "positive" or "negative." Administration and reading of a tuberculin test requires training and experience. Interpretation o f the Test. Although the tuberculin skin test is the only clinically available test to determine the presence of tuberculosis infection in persons who have no symptoms, it is neither 100% sensitive nor completely specific. Of 5000 patients with TB tested in one study, 96% produced measurable induration.17 The average reaction was 16 to 17 mm; few were less than 5 mm. Another study revealed negative skin test results in 20% of sputum-positive persons. 18 Specificity of this test is also quite variable. U.S. Navy recruits, when tested, demonstrated a wide range of tuberculin reactions, the size of which varied according to geographic residence of the recruit. 19Therefore the separation of "significant reaction," suggesting tuberculosis infection, from nonsignificant reaction due to nontuberculous mycobacteria, should not be based solely on size of induration (Table 2). Many factors, such as dose, dilution, tuberculin preparation, and relative prevalence of TB and nontuberculous mycobacteria in the particular geographic area, will influence the outcome. Cross-reactions due to nontuberculous mycobacteria tend to give smaller reactions, but there is no clear point of separation. Since the prevalence of TB infection is greater among close contacts, using 5 m m as a cutoff point is quite appropriate. False-positive skin test results--i.e, positivity due to nontuberculous mycobacter i a - - w o u l d be low in this group. The positive predictive value of the PPD skin test in such a group is high, even if 5 m m is accepted as significant (Table 3). Among persons in w h o m the incidence of TB is very low, 5 or 10 mm induration is likely to be the result o f crossreaction with nontuberculous mycobacteria rather than M. tuberculosis. t5 Hence induration of 15 m m or greater in such a population is DM, March 1 9 9 7

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TABLE 3. Predictive value of PPD positivity

Specificity/Predictive Value (per cent) Prevalence of infection (%) 90.00 25.00 5.00 0.10

0.95

0.99

0.99 0.86 0.50 0.03

0.999 0.97 0.83 0.10

{Adapted from Bass JB Jr. The tuberculin test. In: Reichman LB, Hershfield ES, editors. TubercuIosis: a comprehensive international aproach. New York: Marcell Dekker, 1993:145.)

generally considered significant (Table 2). In those who have no risk factors for TB and who have not been in contact with an active case, using 15 mm as the cutoff point minimizes the false-positive rate, thus improving the positive predictive value (Table 3). Booster Effect. Booster effect is a significant increase in the size of the reaction to a serial test when compared with the first skin test. This phenomenon was first reported by Steele andWillis 2~in 1934 and later proved by other investigators. Transient "amnesia" of the T-lymphocyte or waning delayed hypersensitivity may cause the first test to be negative or less reactive. Repeat testing may stimulate the sensitized T-lymphocytes. While this may occur at any age, it is more common in persons above the age of 50 years. Booster effect may create a problem as it becomes difficult to separate such reaction from true conversion due to recent infection with M. tuberculosis. For this reason, initial two-step testing 1 week apart has been recommended for elderly persons and health care workers who require annual skin testing. 13If the subject remains negative after the second skin test, he or she can then be labeled a "true negative" reactor. Significant reactions in BCG-vaccinated persons should not be assumed to be due solely to B CG. Several studies have demonstrated that (1) the conversion rate (i.e., positive tuberculin test) after B C G vaccine is frequently less than 100%, (2) tuberculin sensitivity often wanes within 8 to 10 years after vaccination, and (3) reaction size from B C G vaccine is frequently quite small. 21'22 Strong reaction to PPD testing (>10 mm) may be due to inhaled bacilli, indicating reinfection. As noted earlier, PPD reactions are not specific for infection with M. tuberculosis. Infection with nontuberculous mycobacteria can also cause positive reaction. In geographic areas of low prevalence, a randomly identified case with positive r e a c t i o n m a y be due to infection from nontuberculous mycobacteria rather than from M. tuberculosis. By contrast, a reactor from a high-risk group (Table 4) or from a developing country is much more likely to be infected with the M. tuberculosis. 16,19 164

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TABLE 4, Preventive therapy for certain high-risk groups Preventive therapy should be recommended for the following persons with a positive tuberculin test reaction, regardless of the individual's age: 9 Those with known or suspected HIV infection 9 Infected close contacts with an active TB case 9 Recent tuberculin skin test converters (_>10 mm induration increase within a 2-year period for those under age 35; _>15 mm induration for persons _>age 35) 9 Those with medical conditions increasing the risk of tuberculosis Preventive therapy is recommended for positive tuberculin test reactors who are <35 years old and in the following high-risk groups, but have no additional risk factors: 9 Foreign-born persons from geographic areas with high prevalence of TB (Latin America, Asia, Africa) 9 Low-income populations, especially minorities and those of certain ethnic groups 9 Residents of long-term care facilities (Adapted from Miller B. Preventive therapy for tuberculosis. Med Clin North Am 1993;77:1263-75.)

PreventiveTherapy According to the Advisory Committee for the Elimination of Tuberculosis, appropriate use of preventive therapy will play a crucial role in the elimination of TB. 23The Centers for Disease Control and Prevention and the American Thoracic Society have jointly issued official recommendations for preventive therapy 24 and periodically publish revisions based on risk/benefit ratio. Persons with HIV infection are the most important group recently added to the list of those recommended to receive chemoprophylaxis for TB (Table 2). 13

Isoniazid Chemoprophylaxis In controlled trials conducted by the Public Health Service, INH preventive therapy reduced the incidence of the disease by 54% to 88% .25Variations in efficacy appear to be influenced by the amount of INH administered and the risk category that led to the recommendation for preventive therapy. Isoniazid chemoprophylaxis has been estimated to be 98% effective among children in Houston and in recently infected nursing home patients who were compliant. 23 Despite its proven efficacy, preventive therapy is underutilized. 26 Unfortunately, INH is not a completely safe drug. A major concern is drug-induced hepatitis, which can be fatal in rare circumstances .27 Understanding Risk Benefit. The recommendation for INH preventive therapy is the most justifiable in cases where the chance of developing TB is the highest; risk of hepatitis is the counter balance. Rate of INH acetylation is no longer considered to be a major risk factor for hepatitis. However, age and alcohol abuse do increase the risk of hepatitis. 27'28 Women DM, March 1997

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tend to carry a higher risk of death from INH-induced hepatitis. 29 The chance of developing tuberculous disease is highest (7% per year) among persons coinfected with HIV? ~It is estimated that HIV infection increases the risk of TB by 113 times; acquired immunodeficiency syndrome (AIDS) increases it by 170 times. Size of the tuberculin reaction is commonly suppressed in persons with HIV infection. 3~Tuberculosis frequently occurs in the early stages of HIV infection when T-cell counts are still above 250. Hence many such patients who are not anergic still have positive skin test reactions (>5 ram). Active TB should be excluded before preventive therapy is started. 24, 25 A second high-risk group comprises recently infected persons with a 3% to 4% chance of developing active disease during the first year of infection. Tuberculin-positive close contacts also are at high risk of developing the disease. Isoniazid preventive therapy recommendations for this high risk group are summarized in Table 4. 31 Several medical conditions are known to increase the incidence of TB among infected persons. For diabetic patients, the risk is two to three times higher than for other infected persons lacking additional risk f a c t o r s . 24' 25 Intravenous drug abuse, chronic steroid therapy, Hodgkin's disease, gastrectomy, silicosis,and loss of 10% or more of body weight have all been linked to increased risk of developing TB. 3~32 Dose and Duration. The usual dose of INH is 10 to 15 mg/kg, not to exceed 300 mg daily. Pyridoxine, 50 rag, is generally administered along with INH to reduce the risk of peripheral neuritis. The optimal duration of chemotherapy is controversial. Six months of INH provides significant protection but may not last for more than 5 years. 33Twelve months of INH has been shown to provide protection for at least 20 y e a r s . 34 Most experts believe that PPD reactors receiving INH preventive therapy for fibrotic chest lesions and coinfection with HIV should receive 12 months of therapy? 4 The American Academy of Pediatrics recommends 9 months of therapy for children. 35A twice-weekly regimen can be used if close supervision is desired. 24 Monitoring. All those receiving preventive therapy should be educated regarding signs and symptoms of toxicity, such as hepatitis and peripheral neuropathy. Although adverse reactions are uncommon, h6'patitis, gastrointestinal symptoms, anemia, and peripheral neuropathy are some of the known side effects of INH. Asymptomatic elevation of liver enzymes is reported in 10% to 20% of patients taking INH. This generally does not require discontinuation of preventive therapy. If SGOT exceeds 250 units or greater than five times normal, INH therapy should be stopped. Baseline liver enzymes followed by periodic liver function tests are recommended 166

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for persons over the age of 35 years; however, this is not a substitute for monthly clinical evaluations. If the patient develops symptoms (commonly gastrointestinal), more frequent biochemical examinations are indicated. The percentages of risk for hepatitis at various ages are listed as follows: age 1 to 20 years--negligible risk; 20 to 24 years--0.3% risk; 35 to 39 y e a r s - - l . 2 % risk, >50 years--2.3% to 3.0% risk. 35 Alcohol consumption is a known risk factor. 35 Rate of acetylation, once thought to be a potential danger, is no longer considered a risk. While the overall incidence of INH hepatitis-related fatality is less than 10%, 36"38 increased susceptibility has been noted among black and Hispanic females. 29,36 Women in the postpartum state are also at greater risk of INH-related hepatitis. 29 Because the interaction of INH and phenytoin increases the serum level of both drugs, frequent assessment of serum phenytoin level is recommended. Reduction in the dose of phenytoin is often necessary. Drug Therapy for Infected Contacts With a Drug-Resistant Case. If a person has developed positive PPD from an INH-resistant case or suffers serious side effects to INH, rifampin (RMP) is generally a good alternative drug choice. For adults, 600 mg of R M P daily for 6 to 9 months is an acceptable alternative to INH chemoprophylaxis. 35 If the patient was infected from a case with both INH and R M P resistance, the selection of preventive agents is somewhat controversial. Once infected, persons at very high risk of developing tuberculous disease with multidrug-resistant organisms (young children, HIV-infected persons) may be administered a regimen consisting of two drugs to which their organisms are likely to be susceptible. Such a regimen might consist of pyrazinamide and quinolone or pyrazinamide and ethambutol for 12 months. 39

Bacille Calmette- Gu~rin Vaccine Use of BCG oral vaccination began in France in 1924, on a modest scale, mostly in children who were in contact with an open TB case. After Calmette's early method of oral vaccine induced only slight tuberculin sensitivity, intradermal vaccination was proposed by Wallgren. 4~ Although used in many countries for decades, there was no convincing evidence that the BCG vaccine actually offered protection against TB. 23 Not only did the vaccine differ widely in its viability, but the various strains of BCG also appeared to have unpredictable rates of efficacy. Although a few studies indicated that the vaccine reduced mortality rates and perhaps helped to prevent tuberculous meningitis and miliary TB in children, 4~ results of a field trial conducted in India clearly established the vaccine's limited scope of usefulness. 42Although the severity of central nervous system and miliary TB in children vaccinated with B C G was low, overall DM, March 1997

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incidence of the disease was no lower among children who received the vaccine than among those who did not. However, several new studies have shown the beneficial effects of BCG vaccination, especially against the serious disseminated form of T B . 43 Administration of the vaccine is indicated as early in life as possible in situations in which the risk of TB infection is high. It has been proved effective in preventing TB in young adulthood and has been used in adolescents in many European c o u n t r i e s . 44' 45 Currently, BCG vaccine is indicated mainly in newborn infants in developing countries or in areas where the risk is very high (->7.1% per year).46 Included in this high-risk category are health care workers in certain geographic areas, particularly where multidrug-resistant TB is prevalent. 46 A rare complication of BCG vaccination is disseminated BCG-related infection, invariably associated with severe immunodeficiency. This is a matter of great concern in view of the fact that the number of infants infected with HIV is on the rise in African countries. By provoking a positive reaction to skin testing, BCG vaccination makes PPD skin testing a less useful tool for identifying high-risk infected persons who could be offered chemoprophylaxis.

Special Strategies/Screening for High-Risk Populations Tuberculosis transmission and the incidence of disease tend to be higher among certain social, ethnic, and age groups.47.48 Populations in the highrisk category include (1) residents of nursing homes and other chroniccare facilities, (2) prison populations, 47 (3) homeless persons, 48 (4) HIVinfected persons, (5) foreign-born/minorities and other socioeconomically deprived populations, and (6) health care workers in certain high-risk areas. Many such persons are poor and have limited access to prompt health care. They often have unique factors that render them more susceptible to the development of active TB. Prevention strategies in such groups often require modification with special emphasis on socioeconomic factors. 48 Although what applies to the United States may not be true throughout the world, every nation has certain populations at especially high risk of TB 49

Nursing Home Residents With a case rate of 100.7 per 100,000 population, elderly nonwhite men have the greatest risk of TB.50 Incidence of the disease is highest among elderly populations regardless of sex, race, or ethnicity. Stead et al. 51 reported that nursing home residents in Arkansas have TB case rates almost five times those of elderly persons living in the community. Special precautions are therefore needed to prevent TB transmission 168

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in long-term care facilities. All residents should undergo preadmission clinical evaluation, including tuberculin testing, to detect active disease. Two-step skin testing is recommended at the time of admission for those who are PPD negative. Recent converters should be administered INH preventive therapy. Skin test status and chest x-ray findings should be accurately documented. Established nursing home guidelines for the respective states should be strictly adhered to. 52 Most policies would include guidelines for prompt diagnosis, treatment, and isolation of active cases in addition to periodic screening of residents to safeguard against ongoing transmission.

Prison Populations Several outbreaks of TB have been identified among prison populations) 3 Since illegal drug use and drug dealing have been classified as serious offenses, the percentage of prisoners incarcerated for drug-related crimes has increased; prisons are overcrowded. Because the incidence of TB is high among drug abusers, appropriate screening at the time of admission and periodic rescreening of inmates is recommended. Prisoners are generally younger than nursing home populations, so INH preventive therapy should be used more often in this group. When proper resources are available, this is an ideal situation in which to monitor for compliance and potential side effects of chemotherapy. Intermittent supervised therapy two or three times weekly is useful and productive. 52,53

Homeless Persons Tuberculosis control efforts toward homeless populations may be more successful through the cooperative efforts of volunteer organizations, community leaders, and church outreach programs? 4 City and state governments all need to work together in identifying and treating active cases. Shelter homes require screening programs to minimize transmission of infection. 48 Special incentive programs, such as free food, clothing, and shelter, may be helpful in achieving directly observed therapy (DOT). Recruiting of health workers who are familiar with local streets, as well as regional cultural and ethnic variances and social issues, is crucial in managing TB among homeless populations3 5

HIV-Infected Persons Persons with HIV infection also tend to have a very high risk of TB transmission. Several outbreaks of multidrug-resistant TB have been reported among such populations. 56 Exogenous reinfection with other strains of mycobacteria during TB treatment creates an additional problem in selecDM, March 1997

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tion of an appropriate treatment regimen. 57Active TB cases in this group generally should be started on a regimen of four to five antituberculosis drugs until susceptibility studies become available. Five millimeters of induration is considered a positive skin test reaction for such persons. For preventive therapy, 6 months' duration is not adequate; 12 months of INH chemoprophylaxis is recommended for those who have contracted TB infection from an INH-susceptible case. 58

Foreign-Born~Immigrants Incidence of active TB and the rate of asymptomatic infection (positive PPD) tend to be high in recent immigrants and foreign-born persons living in the United States and Canada when compared with the native populations. In 1992 foreign-born persons had 27% of the totalTB cases reported in the United States This percentage increased to 34.7% in 1995; of these, 22.5% of the infected persons were born in Mexico. The Philippines and Vietnam ranked second and third, respectively? 8All legal immigrants are screened for active disease before they are granted a permanent visa to enter the United States. However, it is quite difficult to screen illegal immigrants. Since the prevalence of primary drug resistance is high in many developing nations, initially four to five antituberculosis drugs should be used in the treatment of an active case of TB from this population (originating from a geographic area where the incidence of drug resistance is high). 56 Once drug-susceptibility results become available, the drug regimen can be modified. INH chemoprophylaxis should be recommended for symptom-free foreign-born persons if PPD induration is 10 m m or more and risk of INH hepatitis is low29 As described previously, the BCG-induced positive reaction generally wanes after 5 to 10 years. Hence preventive therapy should be considered for foreign-born persons with positive PPD who received BCG vaccination more than a decade earlier. Once again, if the person has no symptoms, preventive therapy should n o t be initiated until active TB is ruled out.

Health Care Workers Health care workers need to take special precautions, particularly if they work in endemic areas or places where the incidence of multidrug-resistant TB is high. 6~Isolation techniques, proper use of masks, and ultraviolet light are all important tools. Skin test conversion among employees has become increasingly common in many fields of health care. In recent nosocomial outbreaks of multidrug-resistant TB, clinical TB developed in at least 17 health care workers. 61 170

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To assess the efficacy of hospital infection control procedures, periodic TB testing for health care workers is essential. All job classifications in a hospital should be stratified for TB exposure risk to determine the frequency of skin testing needed for each employee. Twice-yearly screening is recommended for employees in high-exposure positions, such as emergency department and pulmonary services.56, 62,63All other personnel should be tested a minimum of once a year. It is important to fully understand the booster effect when establishing a TB screening program for hospital employees. Two-step skin testing is recommended for new employees if the first skin test is negative. Once a baseline frequency of tuberculin reactivity is established, each new conversion or high conversion rate within a department should be investigated. Clusters or repeated new conversions in one area suggest deficiencies in isolation technique, delay in disease recognition, or inadequate infection control measures. 46 The Advisory Committee on Immunization Practices recommends BCG vaccination for health care workers who are employed in settings in which the likelihood of transmission and subsequent infection with M. tuberculosis strains resistant to isoniazid and rifampin is high, provided comprehensive tuberculosis infection control precautions have been unsuccessful, a6

Strategiesfor Improving Compliance Patient compliance is a crucial factor in the treatment of any chronic illness. In TB, the word compliance encompasses three components: (1) patient compliance, (2) provider compliance, and (3) adherence to national guidelines.

Patient Compliance Lack of patient adherence to the prescribed antituberculosis therapy is the leading cause of treatment failure and development of drug resistance in TB.64 Directly observed therapy (DOT) is a reliable solution to this problem. 65However, the cost of employing additional health workers to administer DOT (both for treatment and prevention) to high-risk groups is very high, particularly with limited funding for public health departments and when TB control programs must compete with other health-related programs (AIDS, immunization, child health, etc.). Although DOT may be the best way to assure compliance, every patient with TB may not require DOT. ~3Some states have adopted newer, more innovative approaches to ensure patient compliance (Table 5). For example, some areas have recruited c o m m u n i t y volunteers and family members to oversee administration of drug therapy. 66 Others have provided residential facilities in a motel or mobile home park so that one DM, March 1997

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TABLE 5, Methods to improve patient compliance Outpatient clinic 9 Convenient appointment time and location 9 Incentive programs (free transportation, coffee and snacks, baby-sitting services) 9 Appointment reminders (follow-up telephone calls, postcards) Social support 9 Housing facilities for homeless (mobile homes, motels, hospitals) 9 Community volunteer services (food banks, soup kitchens, employment assistance) Directly observed therapy at workplace, home, or clinic Network of volunteer organizations Patient education, improved communication (foreign-language pamphlets, interpreters) Combination drug therapy administered once daily or twice weekly Recognition of side effects and attention to patient rationale for not taking medication

public health worker can supervise several patients in one trip to a designated s i t e . 67 Health departments across the country have played an important role in identifying the problems in patient compliance; however, public health resources are limited and vary from state to state. Nurses and part-time or full-time TB physicians in most public health outpatient clinics supply crucial support to private practitioners by providing comprehensive m a n a g e m e n t of TB. Specific areas of support include the following: 1. Bacteriologic confirmation: Most public health mycobacteriology laboratories in the United States maintain a high-quality and efficient laboratory intended to provide culture confirmation and drugsusceptibility studies. Most private and community hospitals are required to send the initial culture results to the state laboratory for final confirmation. In the United States, in 80% of all cases of pulmonary TB, the culture is confirmed? 8 2. Outpatient services: Tuberculosis control programs in many states provide outpatient clinic facilities; some of these clinics are staffed by experienced nurses and field workers. Others have the luxury of a TB consultant or part-time TB expert who would attend the clinic two to three times weekly. During the clinic visit, diagnosis and treatment modalities are supervised. Side effects to antituberculosis therapy are evaluated. Pill counting, random urine checks, patient education, and several supportive measures are used to assess and assure compliance. Field workers make home visits, carry out contact investigation, and administer directly observed therapy in selected cases, when necessary. Several health departments conduct educational programs for their 172

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staff and other health care providers in the community, all ultimately leading to better understanding of compliance as the major issue in treatment of TB.68

Provider Compliance Several studies indicate that physicians themselves are noncompliant.69 Prescribing inappropriate dose or duration of therapy can lead to treatment failure and drug resistance.7~Lack of physician enthusiasm for INH preventive therapy is a definite hindrance to the success of our national TB elimination plan. vl Physician education, strict adherence to current treatment recommendations, and awareness of patient noncompliance are all important provisions for ensuring provider compliance.

Adherence to National Guidelines Health departments generally do an excellent job of following state and federal policies for management ofTB. However, weakening of the public health infrastructure and lack of resources have made it increasingly more difficult to follow these guidelines precisely.72Periodic quality assessment of TB control programs and in-service seminars may improve the efficiency of public health programs. Funding for such programs may be increased through combined social and political efforts. Recent outbreaks of tuberculosis infection have been reported in churches, bars, and other places where people gather in large numbers, v3.v4 Such mini-outbreaks have demonstrated the need for better surveillance and improved efforts toward contact investigation by public health personnel. Compliance by health care providers and public health agencies becomes an important issue when managed care contracts and capitated health care services put increasing emphasis on reduction of health care costs .75 In addition to general public health regulations, the Occupational Safety and Health Administration (OSHA) in 1993 proposed national standards for control of TB in the workplace. Although establishment of these guidelines is a sign of progress in the fight against TB, their newness and a scarcity of OSHA inspectors make their enforcement a challenge 76

Role of Public Health Department "The history of tuberculosis is the history of mankind.''7v The first national movements to control TB in the United States began in New York in early 1900. vsAlthough almost every state eventually passed TB control laws, it was not the passage of legislation that led to decline of TB in this country. DM, March 1997

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After 1950 a good infrastructure of public health departments combined with the use of modern chemotherapy brought about a rapid decline in the case rate of TB. Since then, resurgence of the disease with approximately 53,000 excess cases occurring between 1984 and 1994 has shaken the TB control programs throughout the United States, resulting in many questions and an urgent need for reevaluation of the issue. A l t h o u g h many p o s s i b l e factors have been identified, poverty, homelessness, substance abuse, and immigration from countries with a high rate of endemicity are considered the leading causes of the return of TB. 79 At the same time, lack of resources, division of health care dollars, and weakening of the public health infrastructure for control of TB were also cited as important factors.77 In a recent review of public health agencies in Washington State, it was estimated that less than 3% of total health-related costs were directed to public health--less than half the amount required, s~ More than 70% of local health departments in the United States have fewer than 100 persons on staff; more than half have fewer than 10 full-time employees. Such health agencies are commonly overwhelmed in their efforts to provide service to those persons lacking access to other medical care. 81 Redistribution of health care funding has assigned a lower priority to TB control programs in same states, 82,83 resulting in a general weakening of the infrastructure of public health, s~ 8~ A false sense of security regarding tuberculosis in the 1980s followed by the diversion of TB resources to AIDS programs in the 1990s has left public health agencies with a heavy burden in diverting control funding for TB programs. Health care reforms have placed greater emphasis on the cost of health care delivery, leading to a decline in public health resources and an inadequate public health infrastructure. 79' 80 The combination of many such factors has indirectly contributed to the resurgence of TB in large urban areas of the United States, primarily impacting poor minority and immigrant populations. 67 A responsible public health approach to infectious epidemics requires surveillance reporting, intervention, and the education of health professionals. 82A 50-state survey of TB statutes and proposals for reform revealed that all of the states have enacted "police power" to control the spread of communicable diseases. 83 Although legal statutes existed in the past, very few states made the appropriate modifications necessary to control TB. Despite the importance of treatment in the quest for TB control, fewer than half the states granted the power to impose treatment. Only 1 1 states have authorized health officers to mandate TB treatment without a court order. Thirty-seven states require a court order for com174

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mitment, and there is considerable variation in the procedural protection afforded to patients. The management of recalcitrant and noncompliant patients is a central feature of TB policy in the United States. This complex problem involves a variety of social, financial, and personal issues. Reform of our health care system is already under way at both the state and federal levels. Although various states have already adopted the policy of "cross training" and are attempting to eliminate categorical services for TB control, some liken such action to "throwing out the baby with the bath water.''84 State and federal governments have tried various strategies to deal with this new crisis. The CDC has developed a nationwide plan 85consisting of three elements: 1. Intensified use of existing prevention, treatment, and TB control methods. 2. Development of new methods of diagnosis and treatment; and, 3. Rapid transfer of new knowledge, skills, and technology into the daily practice of private and public health care. Public health departments must prepare for the challenges entailed in implementing this CDC plan 86 and fulfilling the legislative mandate of controlling communicable diseases. The basic role of public health requires adherence to the following principles: 1. Surveillance-- prompt diagnosis and accurate reporting. 2. Timely initiation of contact investigation and enthusiastic efforts to initiate and complete INH chemoprophylaxis where indicated. 3. Assistance in providing DOT when compliance is in question. Although DOT is not practical in every case of active TB, it is nevertheless more cost-effective in the long r u n . 77 4. Outpatient and inpatient clinical facilities to treat patients with active TB and provide preventive therapy to selected high-risk groups as discussed previously. 5. Providing epidemiologic data. Health departments have traditionally maintainedTB registries. By using modern technology such as computers and electronically networked programs, health departments can improve registry and follow-up data, particularly for recent immigrants and migrant workers who relocate frequently. 6. Assistance in improving patient compliance. Implementation of patient education and incentive programs, DOT, specialized clinical and social services for urban homeless and HIV-infected persons, combined with strong emphasis on treatment and follow-up can lead to more efficient TB control programs, 8688 Institution of a network of volunteer organizations and other corn,

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m u n i t y - b a s e d health care associations. As health care resources continue to decline, cooperative efforts o f private providers and volunteer organizations, such as churches, local lung associations, and academic institutions (medical and nursing schools), will b e c o m e more important. 87 Tuberculosis is a global issue that is correctly described as a "social disease with medical manifestations." It is therefore the responsibility o f public health agencies worldwide to bring social issues into focus for better control o f TB. In the last few decades medical science has progressed to a point where TB is both treatable and preventable. N o w it is up to g o v e r n m e n t agencies, health care provider groups, c o m m u n i t y organizations, and society at large to use these tools to bring the long-held dream o f TB elimination to reality.

References 1. Nardell EA, Riley LR. Precautions to prevent transmission. In: Rossman MD, MacGregor RR. Tuberculosis. New York: McGraw-Hill, 1995:57-72. 2. Wells WF. On airborne infection. II. Droplets and droplet nuclei. Am J Hyg 1934:20:611. 3. Loudon RG, Bumgarner LR, Lacy J, et al. Aerial transmission of mycobacteria. Am Rev Respir Dis 1969;100:165-71. 4. Wells WF, Ratcliffe HL, Grumb C. On the mechanics of droplet nuclei infection: quantitative experimental air-borne tuberculosis in rabbits. Am J Hyg 1948;47:11-28. 5. A NIOSH education document: protect yourself against tuberculosis. U.S. Department of Health and Human Services, DHHS publication No. 96-102, pp 4-10. 6. McDiarmid MA, Gillen NA, Hathan L. Regulatory considerations of occupational tuberculosis control. Occup Med 1994;9:671-9. 7. Riley RL, Kaufman JE. Effect of relative humidity on the inactivation of airborne S e r r a t i a m a r c e s c e n s by ultraviolet radiation. J Appl Microbiol 1972;23:1113, 8. Riley RL, Knight M, Middlebrook G. Ultraviolet susceptibility of BCG and virulent tubercle bacilli. Am Rev Respir Dis 1976;113:413. 9. National Institute of Occupational Safety and Health. Occupational exposure t o ultraviolet radiation. Washington, DC: US Government Printing Office, 1972. 10. Centers for Disease Control. Essential components of a tuberculosis prevention and control program: recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR 1995;44(R- 11): 1-16. 11. Geiter LJ. Preventive therapy for tuberculosis. In: Reichman LB, Hershfield ES, editors. Tuberculosis: a comprehensive approach. New York: Marcel Dekker, 1993: 241-50. 12. Mehta JB, Bentley S. Prevention of tuberculosis in children: missed opportunities. Am J Prev Med 1992;8:283-6. 13. American Thoracic Society. Control of tuberculosis in the United States. Am Rev Respir Dis 1992;146:1623-33. 14. Mehta JB, Dutt AK. Tuberculin skin testing. Int Med J 1994;1:22-7. 15. Mariette ES, Fenger EPK. The present status of the skin reaction in tuberculous and nontuberculous subjects. Am Rev Tuberc 1932;25:357-77. 16. Palmer CE. Nontuberculous pulmonary calcification and sensitivity to histoplasmin. Public Health Rep 1945;60:513-20. 176

DM, March 1997

17. Schein ME Huebner RE. Tuberculin skin testing. In: Rossman MD, MacGregor RR. Tuberculosis. New York: McGraw-Hill, 1995:73-88. 18. Stead WW. The new face of tuberculosis. Hosp Pract 1969;4:62-9. 19. Edwards LB, Acquaviva FA, Livesay VT, et al. An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States. Am Rev Respir Dis 1969;99: 1-132. 20. Steele AH, Willis HS. A study of the increase in sensitiveness in normal children produced by repeated injections of tuberculin. In: Transactions of the 30th Annual Meeting, National Tuberculosis Association. New York, 1934. 21. Comstock GW, Edwards LB, Nabagnkang H. Tuberculin sensitivity 8 to 15 years after BCG vaccination. Am Rev Respir Dis 1971;103:572-5. 22. Guld J. Correlation of tuberculin sensitivity before and after BCG vaccination. Bull WHO 1966;35:479-82. 23. Centers for Disease Control. The use of preventive therapy for tuberculous infection in the United States: recommendations of the Advisory Committee for Elimination of Tuberculosis. MMWR 1990;39(RR-8):9-12. 24. Bass JB Jr, Farer LS, Hopewell PC, O'Brien R, Jacobs RF, Ruben E et al. Treatment of tuberculosis and tuberculosis infection in adults and children. Am Rev Respir Dis 1994;149:1359-74. 25. Comstock GW, Woolpert SF. Preventive therapy. In: Dubica GE Wayne LG, editors. The mycobacteria: a sourcebook. New York: Marcel Dekker, 1984:1071-82. 26. Sorresso DJ, Mehta JB, Harvill LM, et al. Underutilization of isoniazid chemoprophylaxis in tuberculosis contacts 50 years of age and older: a prospective analysis. Chest 1995;108:706-11. 27. Kopanoff DE, Snider DE, Caras GJ. Isoniazid related hepatitis: a US Public Health Service cooperative surveillance study. Am Rev Respir Dis 1978;117:991-1001. 28. Rose DN, Schechter CB, Silver AL. The age threshold for isoniazid chemoprophylaxis. JAMA 1986;256:2709-13. 29. Scharer L, Smith JP. Serum transaminase elevations and other hepatic abnormalities in patients receiving isoniazid. Ann Intern Med 1969;71:1113-20. 30. Selwyn PA, Hartel D, Lewis VA, et al. A prospective study of the risk of tuberculosis among intravenous drug users with immunodeficiency virus infection. N Engl J Med 1989;320:545-50. 31. Bass JB Jr. The tuberculin test. In: Reichman LB, Hershfield ES, editors. Tuberculosis: a comprehensive international approach. New York: Marcel Dekker, 1993:145. 32. Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council. A double-blind placebo-controlled clinical trial of three antituberculosis chemoprophylaxis regimens in patients with silicosis in Hong Kong. Am Rev Respir Dis 1992;145:36-41. 33. International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull WHO 1982;60:555-64. 34. Comstock GW, Baum C, Snider DE Jr. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the Bethel isoniazid studies. Am Rev Respir Dis 1979;119:827-30. 35. Ferebee SH. Controlled chemoprophylaxis trials in tuberculosis in general review. Adv Tuberc Res 1970;17:28-106. 36. Black M, Mitchell JR, Zimmerman HJ, et al. Isoniazid-associated hepatitis in 114 patients. Gastroenterology 1975;69:289-302. 37. Snider DE Jr, Caras GJ. Isoniazid-associated hepatitis deaths: a review of available information. Am Rev Respir Dis 1992;145:494-7. 38. Pessayre D, Bentata M, Degott C, et al. Isoniazid-rifampin fulminant hepatitis: a DM, Ma~h 1997

177

39. 40. 41.

42. 43.

44.

45.

46.

47.

48. 49.

50. 51.

52.

53.

54. 55. 56.

57.

178

possible consequence of the enhancement of isoniazid hepatotoxicity by enzyme induction. Gastroenterology 1977;72:284-9. Villarino ME, Dooley SW Jr, Geiter LJ, Castro KG, Snider DE Jr. Management of persons exposed to multidrug-resistant tuberculosis. MMWR 1992;41(RR-11):59-71. Wallgren A. Intradermal vaccinations with BCG virus: preliminary note. JAMA 1928 ;91:1876-81. Tidjani O, Amedome A, ten Dam HG. The protective effect of BCG vaccination of the newborn against childhood tuberculosis in an African community. Tubercle 1986;67:269-81. Tripathy SP. The case for BCG. Ann Nail Acad Med Sci 1983;19:12-21. ten Dam GH. BCG vaccination. In: Reichman LB, Hershfield ES, editors. Tuberculosis: a comprehensive international approach. New York: Marcel Dekker, 1993:251-74. Smith PG. Case-control studies of the efficacy of BCG against tuberculosis. In: International Tuberculosis. Proceedings of the XXVlth IUAT World Conference on Tuberculosis and Respiratory Diseases. Singapore: Professional Postgraduate Services International, 1987:73-9. Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol 1993 ;22:1154-8. Centers for Disease Control. The role of BCG vaccine in the prevention and control of tuberculosis in the United States: a joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices. MMWR 1996;45(RR-4):1-18. Centers for Disease Control. Prevention and control of tuberculosis in correctional institutions: recommendations of the Advisory Committee for the Elimination of Tuberculosis. MMWR 1989;38:313-20, 325. Schieffelbein CW Jr, Snider DE Jr. Tuberculosis control among homeless populations. Arch Intern Med 1988;148:1843-6. International Union Against Tuberculosis and Lung Diseases (1989). Type of collaboration provided by IUATLD National Tuberculosis Program in developing countries: progress report '89. Volume 1, pp 138-140. Stead WW. Tuberculosis among elderly persons: an outbreak in a nursing home. Ann Intern Med 1981;94:606-10. Stead WW, Lofgren JP, Warren BA, et al. Tuberculosis as an endemic and nosocomial infection among the elderly in nursing homes. N Engl J Med 1985;312: 1483-6. Centers for Disease Control. Prevention and control of tuberculosis in facilities providing long-term care to the elderly: recommendations of the Advisory Council for Elimination of Tuberculosis. MMWR 1990;39(RR-10):7-20. American College of Chest Physicians, American Thoracic Society. Institutional control measures of tuberculosis in the era of multiple drug resistance: ACCP/ ATS consensus conference. Chest 1995; 108:1690-710. Morris JT, McAllister CK. Homeless individuals and drug-resistant tuberculosis in South Texas. Chest 1992;102:802-4. Rubel AJ, Garro LC. Social and cultural factors in the successful control of tuberculosis. Public Health Rep 1992;107:626-36. Centers for Disease Control. Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons: Florida and New York, 1988-1991. MMWR 1991;40:585-91. Small PM, Shafer RW, Hopewell PC, Singh SP, et al. Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection. N Engl J Med 1993;328:1137-44. DM, March 1997

58. Reported tuberculosis in the USA, 1995. US Department of Health and Human Services, CDC Report, 1995; pp 50-1. 59. American Thoracic Society. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994; 149:1359-74. 60. McKenna MT, Hutton M, Cauthen G, Onarato IM. The association between occupation and tuberculosis: a population based survey. Am J Respir Crit Care Med 1996;154:587-93. 61. Maloney SA, Pearson ML, Gordon MT, et al. Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers. Ann Intern Med 1995;122:90-5. 62. Goldman KP. Tuberculosis in hospital doctors. Tubercle 1988;69:237-40. 63. Haley CE, McDonald RC, Rossi L, et al. Tuberculosis epidemic among hospital personnel. Infect Control Hosp Epidemiol 1989;10:204-10. 64. Sbarbaro JA. The patient-physician relationship: compliance revisited. Ann Allerg 1990;64:325-31. 65. Holt E, Cantave M, Johnson M, Clermont HC, Atkinson J, Chaisson RE. Efficacy of supervised, intermittent, short-course therapy of tuberculosis in HIV infection. In: Proceedings, IXth International Conference on AIDS, Berlin, June 7-11,1993 (Abstract No. WS-B09-4). 66. Chaulk CP, Moore-Rice K, Rizzo R, Chaisson RE. Eleven years of communitybased directly observed therapy for tuberculosis. JAMA 1985;274:945-51. 67. Centers for Disease Control. Prevention and control of tuberculosis in U.S. communities with at-risk minority populations: recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR 1992;41(RR-5): 1-11. 68. Etkind SE. The role of the public health department in tuberculosis. Med Clin North Am 1993;17:1303-10. 69. Geiseler PJ, Nelson KE, Crispen RG. Prevention of tuberculosis in physicians: compliance with preventive measures. Am Rev Respir Dis 1987;135:3-9. 70. Miller B, Snider DE. Physician noncompliance with tuberculosis preventive measures. Am Rev Respir Dis 1987;135:1-3. 71. Mehta JB, Dutt AK, Harvill L, et al. Isoniazid preventive therapy for tuberculosis: are we losing our enthusiasm? Chest 1988;94:138-41. 72. Hamburg MA. Rebuilding the public health infrastructure: the challenge of tuberculosis control in New York City. J Law Med Ethics 1993;21:352-9. 73. Dutt AK, Mehta JB, Whitaker BJ, Westmoreland H. Outbreak of tuberculosis in a church. Chest 1995;107:447-52. 74. Kline SE, Hedemark LL, Davies SE Outbreak of tuberculosis among regulars of a neighborhood bar. N Engl J Med 1995;333:222-7. 75. Brown RE, Miller B, Taylor WR, et al. Health-care expenditures for tuberculosis in the United States. Arch Intern Med 1995;155:1595-600. 76. Klitzman S, Kellner P. Control of tuberculosis in the workplace: toward an integration of occupational health and public health. Occup Med 1994;9:723-34. 77. Sbarbaro JA. The plan to eliminate tuberculosis in the United States. In: Reichman LB, Hershfield ES, editors. Tuberculosis: a comprehensive international approach. New York: Marcel Dekker, 1993:629-39. 78. Dubos R, Dubos J. The white plague: tuberculosis, man, and society. Boston: Little, Brown, 1952:120-4. 79. Landesman SH. Commentary: tuberculosis in New York City--the consequences and lessons of failure. Am J Public Health 1993;83:766-8. 80. Gebbie KM. Rebuilding a public health infrastructure. J Law Med Ethics 1993 ;21:368-71. 81. Cahill KA. Imminent peril: public health in a declining economy. New York: 20th Century Fund Press, 1991. DM, March 1997

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82. Annas GJ. Control of tuberculosis--the law and the public's health. N Engl J Med 1993;328:585-8. 83. Gostin LO. Controlling the resurgent tuberculosis epidemic: a 50-state survey of TB statutes and proposals for reform. JAMA 1993;269:255-61. 84. Hopewell PC. The baby and the bath water; the case for retaining categorical services for tuberculosis control in a reformed health care system. Am J Respir Crit Care Med 1994;150:895. 85. Centers for Disease Control. Initial therapy for tuberculosis in the era of multidrug resistance: recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR 1993;42(RR-7):1-8. 86. Centers for Disease Control. Tuberculosis control laws--United States, 1993. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR 1993;42(RR-15):1-28. 87. Freudenberg NE A new role for community organizations in the prevention and control of tuberculosis. J Community Health 1995;20:15-28. 88. Miller B. Preventive therapy for tuberculosis. Med Clin North Am 1993;77:126375.

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