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Tuberculosis in the Workplace 2 Basics of Tuberculosis Although tuberculosis has two general states, latent infection and active disease,1 only those who develop active tuberculosis can transmit the disease. Table 2-1 summarizes the basic differences between latent tuberculosis infection2 and active pulmonary tuberculosis, which is the most common form of the disease. An understanding of both latent tuberculosis infection and active tuberculosis is needed to develop effective policies and programs to prevent and control transmission of tuberculosis in communities generally and in workplaces specifically. Detection and treatment of active, transmissible disease is the highest priority for both clinicians and public health officials. Detection and, in certain cases, treatment of latent tuberculosis infection is also important. For an infected individual, treatment helps prevent progression to active disease. For the broader community, detection and treatment of infection contribute to the broader public goal of tracking and eliminating tuberculosis. This chapter briefly reviews how latent tuberculosis infection and active tuberculosis develop and are diagnosed and managed. 1 This chapter’s discussion of infection, disease, and transmission draws on the works of Haas and Des Prez (1995), Daniel (1997), Gangadharam and Jenkins (1998), Reichman and Hershfield (2000), ATS/CDC (2000a,b), and CDC (2000a). 2 As noted in Chapter 1, this report treats “infection with Mycobacterium tuberculosis,” “latent tuberculosis infection,” and “tuberculous infection” as synonyms.
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Tuberculosis in the Workplace TABLE 2-1. Differences Between Latent Tuberculosis Infection and Active Pulmonary Tuberculosis Latent Tuberculosis Infection Active Tuberculosis (in the lungs) Few tuberculosis bacteria in the body Many tuberculosis bacteria in the body Tuberculin skin test reaction usually but not always positive Tuberculin skin test reaction usually but not always positive Chest radiograph normal Chest radiograph usually abnormal Sputum smears and cultures negative Sputum smears and cultures usually positive No symptoms Symptoms (e.g., cough) often present Not infectious Potentially infectious before treatment SOURCE: Adapted from CDC (1999c, Module 1, p. 7). TRANSMISSION AND DEVELOPMENT OF LATENT TUBERCULOSIS INFECTION AND ACTIVE TUBERCULOSIS Tuberculosis is primarily caused by Mycobacterium tuberculosis (also called the tubercle bacillus). Humans can also develop bovine tuberculosis, a less serious disease that is primarily caused by drinking milk from cattle infected with Mycobacterium bovis.3 Other mycobacteria can cause tuberculosis in various animals, but they rarely cause disease in humans.4 As discussed later in this chapter, bovine and other mycobacteria may produce positive reactions to the tests used to screen people for tuberculosis. Although M. tuberculosis was first identified in 1882, its behavior remains poorly understood in some important respects. In particular, much remains to be learned about the mechanisms of latent tuberculosis infection and disease activation and reactivation. Transmission of M. tuberculosis M. tuberculosis typically spreads through the air when people who have infectious tuberculosis in their respiratory tract cough, sneeze, speak, sing, or otherwise expel tiny particles containing the bacteria. A fine mist (an aerosol) of infectious particles can also be created in other ways, for 3 In developed countries, bovine tuberculosis has largely been eliminated by programs of tuberculin testing in cattle followed by slaughter of infected animals. Infected cattle, deer, and other animals are still occasionally found in the United States, and human cases continue to be reported (Dankner and Davis, 2000; Hernandez and Baca, 1998; Palmer et al., 2000; Pillai et al., 2000; Schmitt et al., 1997). Aside from testing and destruction of infected animals, public health programs rely on compulsory pasteurization and certification of milk to prevent transmission of the disease to humans. 4 For patients with AIDS, Mycobacterium avium complex disease can be life-threatening, but information about its epidemiology and effective management is limited (Gangadharam and Jenkins, 1998).
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Tuberculosis in the Workplace example, during a procedure to irrigate a tuberculosis-infected abscess, during laboratory processing of infected tissue, or during an autopsy or embalming.5 Whether produced by coughing or other actions, most of the largest, heaviest bacterium-bearing particles will settle fairly quickly and harmlessly on surfaces such as walls, furniture, and clothing. Some airborne particles will reach another person’s nose and throat but will be trapped and then removed when the person swallows or spits. The smallest, lightest particles (called droplet nuclei) may reach the lung’s alveoli, which are the tiny, endmost parts of the respiratory tract and the starting point for most tuberculosis infections. In poorly ventilated spaces, droplet nuclei may stay in the air for hours or even days. The bacteria are very sensitive to sunshine and other ultraviolet light. Extended, close, indoor contact is usually required for tuberculosis to be transmitted from one person to another. At least one report has, however, documented transmission after workplace exposure limited to a few minutes (Templeton et al., 1995). Tuberculosis is considered moderately infectious, with infection developing in perhaps 30 to 50 percent of those who have extended, close, indoor contact with people with active disease. Measles, by contrast, is considered highly infectious, with infection developing in an estimated 80 percent of susceptible people who come in contact with an infected individual (Haas and Des Prez, 1995). The likelihood that M. tuberculosis will be transmitted from one person to another depends on several factors. These factors include the infectiousness of a person with infectious tuberculosis, which is related to the number of bacteria he or she expels and, possibly, the virulence (disease-causing potential) of the bacteria; the length of exposure to an infectious person or to air contaminated with tuberculosis bacteria; the environment surrounding an infectious person, for example, the size of a room and how well it is ventilated; and the functioning of an exposed person’s immune system. Infection with M. tuberculosis Typically, when tuberculosis bacteria reach the alveoli in the lungs, they attract and are engulfed by white blood cells called macrophages.6 The bacteria multiply within the macrophages, and some may escape and 5 Transmission by other routes has also been reported (e.g., from inadequately sterilized bronchoscopes, accidental self-inoculation, and a kidney transplant) (Dooley and Tapper, 1997). 6 This is a greatly simplified description of a very complex pathological process, aspects of which are still not fully understood.
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Tuberculosis in the Workplace spread through the lymph system and the bloodstream to other sites in the lungs as well as the brain, bone, and kidneys. The most common site of infection—and active tuberculosis—is the upper part of the lungs. As they spread, the tuberculosis bacteria will usually provoke a further, more powerful infection-fighting response that physically contains the bacteria in hard, immune-cell clusters called granulomas. (Tuberculous granulomas are called tubercles.) This process normally stops further multiplication and spread of the bacteria. Some bacteria may, however, remain alive within a granuloma for years, even decades. This condition is described as latent infection with M. tuberculosis. As described below, the surviving bacteria have the potential to cause active tuberculosis at a later time. A successful immune response to tuberculosis bacteria generally takes between 2 and 10 weeks to develop. The great majority of those with latent tuberculosis infection never develop active disease, have no symptoms, and do not infect others. No national data on tuberculosis infection are available. Estimates prepared for the Occupational Safety and Health Administration (OSHA) put the prevalence of latent tuberculosis infection in the United States in 1994 at about 6 to 7 percent of the population over age 18 years (62 FR 201, October 17, 1997). As discussed in Chapter 5 and Appendix C, rates of infection and disease vary considerably among racial, ethnic and other population subgroups. Active Tuberculosis It is often stated that an estimated 10 percent of those infected with M. tuberculosis will develop active tuberculosis if their latent infection is not treated (see, e.g., CDC [2000a]). This number has, however, been questioned (see Chapter 7 and Appendix C), and it likely overstates the risk for most workers, in part because the rate of progression from untreated infection to active disease varies by age. Studies conducted in the 1960s and 1970s indicate peaks in progression for young children (approximately ages 1 to 4) and for those in adolescence and early adulthood (approximately ages 13 to 24) (Comstock, 2000) .7 Rates for working-age adults are lower. Studies suggest that the highest risk of progression to active disease is during the first 1 to 2 years following infection with M. tuberculosis. As discussed further below, treatment of latent tuberculosis infection substantially reduces the risk of progression to active disease. 7 Age-specific disease patterns differ in high- versus low-prevalence countries (Comstock, 2000; Daniel, 2000). In the latter, rates show a sharp peak during the postpuberty, young-adult years. In low-prevalence countries, a higher proportion of cases arises in elderly people.
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Tuberculosis in the Workplace Several medical conditions can limit a successful immune response to tuberculosis infection and increase the likelihood of disease progression. Such conditions include human immunodeficiency virus (HIV) infection and AIDS, diabetes mellitus, silicosis, chronic renal failure, some cancers, advanced age, weight significantly less than recommended levels, and treatment with drugs that suppress immune system functioning. The risk of progression from untreated tuberculosis infection to active tuberculosis is particularly high in people with HIV infection or AIDS—approximately 10 percent per year. The Centers for Disease Control and Prevention (CDC) has recommended that health care workers with HIV infection be offered voluntary reassignments that minimize contact with patients with suspected or confirmed active tuberculosis (CDC, 1994b). About 80 percent of cases of active tuberculosis involve the lungs (pulmonary tuberculosis), either exclusively or in combination with other sites (CDC, 1999b). The other most common sites of active tuberculosis are the lymph nodes, brain, bones, and kidneys. Those with extrapulmonary tuberculosis and no coexisting pulmonary or laryngeal disease rarely infect others because the bacteria lack an easy route (i.e., the respiratory tract) to airborne transmission. Children and people with HIV infection are more likely than others to develop extrapulmonary forms of tuberculosis. Without treatment, fatality rates for those with active tuberculosis may exceed 50 percent (Haas and Des Prez, 1995). With treatment, death rates drop to near zero for people who have well-functioning immune systems and drug-sensitive disease and who receive timely, appropriate care (Cohn et al., 1990; Combs et al., 1990). Among patients infected with multidrug-resistant strains of tuberculosis (especially patients with poorly functioning immune systems), death rates even with treatment may be as high as 90 percent (CDC, 1994b; Garrett et al., 1999). DETECTION AND TREATMENT OF LATENT TUBERCULOSIS INFECTION Testing for Latent Tuberculosis Infection The tuberculin skin test is the only currently available diagnostic tool for the detection of latent infection with M. tuberculosis.8 Although gen 8 In areas where tuberculosis is uncommon, screening of the general population by the tuberculin skin test is not recommended (ATS/CDC, 2000b). Targeted testing is recommended for people who are thought to be at higher risk of developing disease and who would benefit from treatment of latent infection. High-risk groups include people with HIV infection and certain other medical conditions, recent immigrants from countries where tuberculosis is common, and those with recent exposure to someone with infectious tuberculosis. Treatment for latent tuberculosis infection should be available to those who have positive tuberculin skin test results.
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Tuberculosis in the Workplace eral population screening is not recommended in areas where active tuberculosis is uncommon, testing at the start of employment and sometimes periodically thereafter has been advised for otherwise low-risk individuals who work in health care facilities, prisons, or other settings that serve or house higher-risk populations. As discussed in Chapter 4, the 1994 CDC guidelines for health care facilities and the rule proposed by OSHA in 1997 provide for slightly different workplace programs for skin testing. A CDC advisory committee has recommended a reexamination of the 1994 recommendations, and a CDC working group recently began that process. The following discussion identifies some of the limitations of tuberculin skin testing (see also Appendix B). Administering and Interpreting the Tuberculin Skin Test To conduct a tuberculin skin test, a specified amount of tuberculin (a preparation made from killed tuberculosis bacteria) is injected into the skin of the forearm by a health care worker trained in the procedure. The only skin testing procedure recommended by CDC is the tuberculin skin test with PPD (a purified protein derivative of tuberculin). After the injection, a reaction to the tuberculin skin test in an infected individual will generally occur and should be examined within 48 to 72 hours. A reaction should be interpreted by a physician or other trained health care worker who should follow a specific protocol to measure the raised, hardened area (induration) around the injection site. (Redness may also develop around the test site but is not considered in interpreting the test.) Interpretation is based on the size of the reaction site and certain characteristics of the tested individual. For example, a 5- or 10-millimeter (mm) reaction may be classified as a negative response in an individual with no risk factors for disease but as a positive result in someone who does have risk factors. Absence of a reaction is recorded as 00 mm. Table 2-2 shows CDC recommendations for interpreting skin test reactions. For groups being tested periodically as part of a tuberculosis surveillance program, both the number and rate of reactions and the rate of conversions from negative to positive test results are of interest. A conversion is generally defined as an increase of 10 mm or more in the reaction size within a 2-year period from the last test. Such a conversion is generally interpreted as indicating recent infection with M. tuberculosis. (As described below, high rates of false-positive test results are a concern in some environments.) Conversions are typically investigated to assess the possibility of workplace-related exposure to tuberculosis. To assess the possibility of community exposure, workers whose tests have converted may be questioned about possible contacts with family members or friends outside work who have active tuberculosis.
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Tuberculosis in the Workplace TABLE 2-2. CDC Recommendations for Interpreting Reactions to the Tuberculin Skin Test I. Classify induration of ≥5 mm as positive for • HIV-positive persons • Recent contacts of individuals with tuberculosis • Persons with fibrotic changes on chest radiograph consistent with prior tuberculosis • Organ transplant recipients and others with conditions or treatments that suppress their immune systems II. Classify induration of ≥10 mm as positive for • Recent immigrants (within 5 years) from high-prevalence countries • Injection drug users • Residents and employees of high-risk congregate settings: prisons and jails, nursing homes and other long-term care facilities for elderly, individuals, hospitals and other health care facilities; residential facilities for AIDS patients, homeless shelters* • Mycobacteriology laboratory personnel • Persons with diabetes and other clinical conditions (other than those identified in category I) that place them at high risk • Children under 4 years of age or children and adolescents exposed to adults in high-risk categories III. Classify induration of ≥15 mm as positive for • Persons with no known risk factors for tuberculosis *For employees who are otherwise at low risk and who are tested upon hiring, an induration of ≥15 is considered positive. SOURCE: Adapted from ATS/CDC (2000a). Measures of Test Accuracy Several measures have been developed to help in assessing the accuracy and utility of screening tests (Daniel and Daniel, 1993; USPSTF, 1996). Sensitivity is defined as the proportion of people with a condition (e.g., infection with M. tuberculosis) who have positive test results.9 The lower the sensitivity of a test, the more likely a test will miss people who actually have the disease or condition but show false-negative test results. The sensitivity of the tuberculin skin test has been estimated at 95 percent except for those with active tuberculosis or very recent infection (ATS/ CDC, 1999a, Appendix B). The specificity of a test is defined as the proportion of people without the condition who have negative test results. The lower the specificity of a test, the more people who do not have the condition will show false-positive results and be told that they do have it. Specificity for the tuberculin skin 9 Calculation of sensitivity and specificity requires some way of identifying those with the condition who have negative results. (For the tuberculin skin test, the condition is latent tuberculosis infection.) This requires a “gold standard” reference test, which does not exist for many common screening tools, including the tuberculin skin test.
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Tuberculosis in the Workplace TABLE 2-3. Positive Predictive Value of a Positive Tuberculin Skin Test Assuming 95 Percent Sensitivity Predictive Value (%) at the Following Specificity Prevalence of Infection (%) 95% 99% 99.5% 90.0 99.4 99.9 99.9 50.0 95.0 99.0 99.5 25.0 86.4 96.9 98.4 10.0 67.9 91.3 95.5 5.0 50.0 83.3 90.9 2.0 27.9 66.0 79.5 1.0 16.1 49.0 65.7 0.1 1.9 8.7 16.0 0.05 0.9 4.5 8.7 0.01 0.2 0.9 1.9 SOURCE: ATS/CDC (2000a), with recalculation to correct predictive values for 0.01 percent prevalence. test has been estimated at 99 percent or better in areas where exposure to other mycobacteria is uncommon and at 95 percent in areas where such exposure is relatively common (ATS/CDC, 1999a, Appendix B). A third measure helpful in assessing the usefulness of a screening test is its positive predictive value, which is defined as the probability of a disease or condition in a tested person given a positive test result. A test’s positive predictive value is affected by the prevalence of the disease or condition in the community of those being tested.10 Table 2-3 illustrates how prevalence affects calculations of positive predictive value for the tuberculin skin test. Another way of understanding the effect of disease or condition prevalence relies on Bayesian analysis, as shown in Table 2-4. Given the sensitivity and specificity levels assumed in the table, the positive predictive value—the probability of infection given a positive test result—drops from 49 to 8.7 percent when the prevalence of infection in the community drops from 1 to 0.1 percent. Thus, even for a reasonably sensitive and specific test, the lower the prevalence of a disease or condition, the higher the proportion of false-positive results. In very low-prevalence areas, a majority of positive test results will be false positives.
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Tuberculosis in the Workplace TABLE 2-4. Importance of Disease or Condition Prevalence, Bayesian Probability Analysis Test conditions: sensitivity of test, 95 percent specificity of test, 99 percent Patient Status Prior Probability (%) Probability of a Positive Skin Test (%) Product of Probabilities (col 1 * col 2) (%) Revised Probability (col 3I * 100/ sum col 3) (%) If prevalence is 1% TB infection 1 95 95 49.0 No TB infection 99 1 99 Sum = 194 51.0 If prevalence is 0.1% TB infection 0.1 95 9.5 8.7 No TB infection 99.9 1 99.9 Sum = 109.4 91.3 NOTE: TB = tuberculosis. For individuals, false-negative results are a concern because of the lost opportunity for treatment to reduce their likelihood of developing active tuberculosis. False-positive results are a concern because they may lead to unneeded and potentially harmful treatment for someone who does not actually have latent tuberculosis infection. They can also provoke considerable anxiety. In some situations, a positive test result may be socially stigmatizing. For public and occupational health personnel, false-negative test results may lead to missed opportunities to control the transmission of tuberculosis and identify weaknesses in community or workplace control measures. False-positive results may lead to unnecessary use of limited resources for investigations and medical follow-up. Other Limitations of the Tuberculin Skin Test A number of factors can lead to false-positive or false-negative readings for a tuberculin skin test. They include The inadequate conduct or management of the skin test or the skin testing program. With good training and careful practice, the tuberculin skin test is not difficult to administer correctly and to interpret accurately and consistently. A lack of resources and inadequate training and oversight can, however, jeopardize the proper storage of the test material, the quality of testing procedures, and the appropriate recording and use of test results (Chaparas et al., 1985; Ozuah, 1999; see also Perez-Stable and Slutkin ). In addition, differences in the products (reagents) used in
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Tuberculosis in the Workplace the test and in different batches of the same product may produce variable results (Villarino et al., 1999; Blumberg et al., 2000). The possibility that repeated skin tests may stimulate a reaction in those with long-standing latent tuberculosis infection (a response called boosting). If people infected many years ago have not been tested recently, some will incorrectly test negative on a tuberculin skin test (a false-negative result). The test itself may then stimulate—boost—their sensitivity to tuberculin. If given a second test a few weeks or months later, these individuals may correctly test positive. This boosted reaction can be mistaken for evidence of exposure to tuberculosis and new infection. To control for this phenomenon, workplace surveillance programs may provide two-step baseline testing (two skin tests given 1 to 4 weeks apart). In this context, a positive result for the second test following a negative result for the first test is interpreted as a boosted result rather than as a true conversion. A worker with a boosted test result would not be included in a periodic retesting program. The difficulty of interpreting test reactions in people who have been vaccinated against tuberculosis with BCG. Bacille Calmette and Guérin (BCG) vaccination is uncommon in the United States but fairly common in Europe and elsewhere.11 Thus, many immigrants to the United States have been vaccinated and may show false-positive reactions to the tuberculin skin test. The geographic prevalence of other mycobacteria that produce reactions to tuberculin. In the southeastern United States (especially coastal areas) and other similar locales around the world, common exposure to mycobacteria other than M. tuberculosis can produce false-positive tuberculin skin test results. The existence of anergy (failure of a person with tuberculosis infection to react to a tuberculin skin test). Approximately 10 to 25 percent of those with active untreated tuberculosis may have no reaction to the tuberculin skin test (CDC, 2000a). Anergy can be caused by immunosuppression related to HIV infection and certain other infections, poor nutrition, certain drugs and vaccinations, and a number of other factors. Although procedures that can be used to test for anergy exist, the interpretation and accuracy of these tests are uncertain, and CDC and others do not recommend their routine use (CDC, 1997; Slovis et al., 2000). 11 As described by CDC, “BCG vaccines are live vaccines derived from a strain of Mycobacterium bovis that was attenuated by Calmette and Guérin at the Pasteur Institute in Lille, France (29). BCG was first administered to humans in 1921. Many different BCG vaccines are available worldwide. Although all currently used vaccines were derived from the original M. bovis strain, they differ in their characteristics when grown in culture and in their ability to induce an immune response to tuberculin” (CDC, 1996c, p. 5). Although it is common in many European and other countries, the CDC does not recommend BCG vaccination except in rare circumstances.
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Tuberculosis in the Workplace The lag between the earliest stages of infection and the ability of the tuberculin skin test to detect infection. The tuberculin skin test depends on what is called a delayed-type hypersensitivity reaction that generally does not develop for 2 to 10 weeks after initial infection. These additional limitations of the tuberculin skin test need to be recognized in implementing skin testing programs and developing policy recommendations and requirements for community and workplace programs for tuberculosis surveillance. As recommended in the recent Institute of Medicine report on the elimination of tuberculosis in the United States (IOM, 2000) and discussed further in Chapter 7, better screening tests are needed to detect latent tuberculosis infection more quickly and more accurately. Treatment of Latent Tuberculosis Infection Treatment of latent tuberculosis infection helps reduce the likelihood that the infection, especially recent infection, will progress to active disease. Treatment of latent tuberculosis infection is also a major element in public health strategies for the elimination of tuberculosis in the United States because it reduces the proportion of people who will develop active, transmissible disease (IOM, 2000). Thus, treatment benefits both the infected individual and the broader community, including workplaces. Completion of a recommended treatment regimen is estimated to cut the rate of progression from infection to disease by about 80 to 90 percent (ATS/CDC, 2000b). Recommendations for Treatment of Latent Infection The drugs used to treat latent tuberculosis infection are a subset of the drugs used to treat active disease, although specific treatment regimens vary. Because treatment of latent tuberculosis infection is not risk-or inconvenience-free, it is usually aimed at individuals at higher risk of developing active disease including those with recent infection and those with AIDS or other conditions that place them at higher risk of progression. Selection of a treatment regimen depends on the characteristics of the person being treated, for example, whether the person has HIV infection or whether he or she is at high risk for failing to complete the full course of treatment. Alternative regimens vary in their potential risk, and burdens. Therefore, patients should be carefully advised of the options and their possible consequences. Patient preferences need to be considered in selecting a regimen.
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Tuberculosis in the Workplace The regimen most highly recommended by ATS and CDC (based on nonrandomized clinical trials) involves 9 months of daily or twice-weekly doses of isoniazid. The twice-weekly regimen is recommended only if the taking of the medication is directly observed (ATS/CDC, 2000b). An “acceptable,” shorter isoniazid regimen for those without other risk factors involves 6 months of daily or twice-weekly doses of the drug (the latter only with direct observation). The shortest, currently acceptable regimen involves two drugs, rifampin and pyrazinamide, taken daily for 2 months. Side Effects of Treatment The major concern about treatment of latent tuberculosis infection has been the potential for liver damage. A recent analysis of 7 years of experience at a Seattle public tuberculosis clinic suggests that the risk of liver damage form the most widely used drug (isoniazid) is lower than previously thought—less than 0.2 percent, compared with the 0.5 to 2.0 percent reported from earlier studies (Nolan et al., 1999). Other analyses (Salpeter, 1993; Garcia Rodriguez et al., 1997) have also suggested risks of adverse treatment effects that are lower than assessed earlier. Those at possible increased risk of liver damage include those who use alcohol daily, those with preexisting liver disease, older people, and pregnant or postpartum women (ATS/CDC, 2000b). Liver damage is also a concern with the rifampin-pyrazinamide treatment regimen, which is being closely monitored as more experience with the regimen accumulates (CDC, 2000c). Careful screening, patient education about signs and symptoms of hepatitis, and prompt discontinuation of drugs when symptoms occur can reduce or eliminate the potential for adverse effects (ATS/CDC, 2000b). Baseline testing of liver function is recommended for patients at risk for liver disorders and for patients who have a history of liver disease, are infected with HIV, use alcohol regularly, or are pregnant or within 3 months of having given birth. In addition, monthly laboratory monitoring of liver function is advised for patients who have abnormal results on baseline liver function tests or who are otherwise at risk for hepatic disease. Nonetheless, for people with an infection that produces no symptoms and that usually has a fairly small chance of progressing to active disease (which usually can be successfully treated), even a very small possibility of liver damage or death may dissuade them from treatment of latent infection. Depending on the drug, less serious adverse reactions include rashes, gastrointestinal upsets, fever, and joint pain (ATS/CDC, 2000b). Some of these reactions may be bothersome enough to prompt a switch to another drug—or abandonment of therapy altogether. As with other treatments, careful communication of risks
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Tuberculosis in the Workplace and benefits is important, perhaps more so when much of the expected benefit will accrue to the broader community, not just the individual.12 Adherence to Treatment for Latent Infection One consideration in the choice among alternative drug regimens is the trade-off between the higher degree of efficacy of a longer duration of treatment and the lower levels of individual adherence to such regimens. A number of studies suggest that rates of initiation and completion of treatment of latent tuberculosis infection are sometimes quite low. One study of an indigent urban population found that only 55 of 466 people with tuberculosis infection were prescribed drug therapy and only 20 of those completed it (Schluger et al., 1999). Another study involving high-risk inner-city residents identified 809 people with a positive skin test result of whom 409 fit ATS/CDC criteria for therapy for latent tuberculosis infection; only 84 (20 percent) actually completed treatment (Bock et al., 1999). Although the rate of treatment adherence might be expected to be high among health care workers, studies suggest otherwise. For example, one study found that only 8 to 10 percent of physicians whose skin tests had converted from negative to positive had been treated for latent tuberculosis infection (Ramphal-Naley et al., 1996). In another study, of 40 health care workers who were identified as having been eligible for isoniazid treatment following a skin test conversion, only 15 (38 percent) had completed at least 6 months of therapy (Fraser et al., 1994). The highest rates of completion of treatment among health care workers were reported in a study of a hospital in a city with relatively high rates of active tuberculosis (Blumberg et al., 1996). Of 125 workers with a recent positive tuberculin skin test result, all got a chest radiograph and almost all (98 percent) saw a physician. Although 84 percent started therapy for latent tuberculosis infection, only 66 percent of those who started therapy completed at least 6 months of treatment. Almost three-quarters of the 34 physicians in the group completed therapy whereas not quite half (44 of 91) of other workers completed therapy. Of all those who started but did not complete treatment, one-third stopped because of side effects. 12 Studies suggest that people often misunderstand numerical explanations of risks and benefits provided by health professionals (Schwartz et al., 1997). How information is provided is important (Ransohoff and Harris, 1997). For example, people may find it easier to understand frequency information (e.g., a 4 in 1,000 chance of some outcome) than probability information (e.g., a 0.4 percent chance of the outcome) (Gigerenzer, 1996). They may also better understand comparisons of absolute risk to a baseline (e.g., reduction in risk to 4 in 1,000 with treatment compared to 12 in 1,000 without treatment) than they understand presentation of relative risk information with no baseline (Schwartz et al., 1997). Treatment may appear more attractive when described in terms of gain (e.g., 99 percent of patients will not develop the disease) rather than loss (e.g., 1 percent will develop the disease) (Mazur and Hickam, 1990; Hux and Naylor, 1995).
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Tuberculosis in the Workplace DIAGNOSIS AND TREATMENT OF ACTIVE TUBERCULOSIS Diagnosis Both the 1994 CDC guidelines on tuberculosis control for health care facilities and the 1997 proposed OSHA rule on tuberculosis control emphasize the fact that prompt identification, isolation, and treatment of people with infectious tuberculosis is critical to an effective tuberculosis control program. Following several outbreaks of tuberculosis in hospitals and other settings, CDC, OSHA, state health departments, and others initiated educational programs to make physicians, nurses, and others more aware of the symptoms of infectious tuberculosis. Nonetheless, as described below, prompt identification of infectious tuberculosis is complicated because symptoms are not highly specific to the disease. Symptoms and Diagnostic Steps According to CDC’s case reporting requirements (CDC, 1999b), a laboratory definition of a case of tuberculosis requires either the isolation of M. tuberculosis from a clinical specimen or demonstration of acid-fast bacilli in a clinical specimen when a culture was not or could not be obtained. (The processing of laboratory smears of sputum or some other specimen uses a dye that leaves only mycobacteria colored after processing with an acid-alcohol solution. The bacteria are thus often described as acid-fast bacilli [AFB] and the smears as AFB positive or negative.) The clinical case definition of tuberculosis requires all of the following: a positive tuberculin skin test result, other signs and symptoms compatible with active tuberculosis (e.g., abnormal and unstable radiologic findings and persistent cough), treatment with two or more antituberculous medications, and a completed diagnostic evaluation. This clinical definition is for reporting purposes. Physicians may begin treatment of individuals with suspected infectious tuberculosis on the basis of symptoms and risk factors while awaiting test results. Common symptoms of pulmonary tuberculosis include chronic cough, a cough that produces sputum, chest pain associated with coughing, and less commonly, coughing up of blood. Other symptoms, which also appear in nonpulmonary tuberculosis, include fever, weight loss, night sweats, and fatigue. Some people with infectious tuberculosis report less specific symptoms or, rarely, no symptoms. The higher the prevalence of active tuberculosis in the community, the higher “the index of suspicion” should be that those with symptoms warrant further evaluation. Diagnostic evaluation of someone suspected of having active tuberculosis involves
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Tuberculosis in the Workplace a medical history that includes questions about symptoms, possible exposure to someone with infectious tuberculosis, past history of the disease, country of origin, age, place of work, and other medical conditions such as HIV infection associated with higher risk of tuberculosis; a physical examination; a chest radiograph to look for abnormalities suggestive of active pulmonary tuberculosis (or signs of infection or past tuberculosis that might warrant treatment); and laboratory tests for evaluation of sputum samples.13 Laboratory samples are usually first assessed with a smear that can be quickly processed to provide a report within 24 hours. Smears allow the identification of mycobacteria but not the identification of M. tuberculosis specifically. A follow-up culture will produce more accurate and specific information, but even with the latest technology, reports will generally not be available for several days. Tests to evaluate drug susceptibility may be done sequentially after culture confirmation of disease, thus adding further to delays in starting appropriate treatment. Molecular analysis (DNA fingerprinting) compares isolates of M. tuberculosis recovered from different individuals. Such analysis can help establish a chain of transmission that links new cases of active disease to source cases. It sometimes allows cases of active tuberculosis among workers to be more accurately linked to previously identified cases in the community or the workplace than was previously possible. The establishment of such links can help guide tuberculosis control efforts. As discussed in Chapter 5, uncertainty about the origins of tuberculosis infection and disease among health care and other workers contributes to uncertainty about the value of regulations in the control of occupational exposure. Some health care worker groups with the high rates of positive skin test results come from populations with high rates of active tuberculosis in the community (Appendix C). Current tests cannot identify the source of tuberculosis infection. Improving Diagnostic Timeliness and Accuracy Failures to promptly identify, isolate, and treat those with diagnosed or suspected infectious tuberculosis are major weak points in programs to prevent occupational exposure to the disease. Unfortunately, community-and workplace-based efforts to improve timely and accurate diagnosis of 13 A tuberculin skin test is optional. Even if it is negative, it does not rule out the disease, especially in someone with symptoms or risk factors such as HIV infection or recent (less than 10 weeks) exposure to a person with infectious tuberculosis. For those with possible nonpulmonary tuberculosis, testing may involve blood, bone marrow, and other tissue.
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Tuberculosis in the Workplace infectious tuberculosis face a significant obstacle: the common symptoms of active tuberculosis are not highly specific to the disease. Particularly in areas where the disease has been rare for a considerable period, physicians are more likely to think of other, more common conditions—for example, bronchitis or lung cancer—when they see someone with symptoms such as a persistent cough. Clinicians likewise may not initially link radiologic signs of active tuberculosis to the disease. Moreover, some individuals with active tuberculosis, especially those with HIV infection, may show radiologic signs that are not typical of the disease, and a few may experience no symptoms. In addition, as tuberculosis has become less common and clinicians and laboratory personnel see fewer instances of the disease, it becomes more difficult for them to maintain proficiency in obtaining, processing, and accurately interpreting specimens. Two recent reviews of episodes of tuberculosis transmission in health care facilities found that nearly all instances involved source cases with undiagnosed and untreated disease (Dooley and Tapper, 1997; Garrett et al., 1999). Many also involved lapses in infection control processes. In several instances, the patient identified as the source case had atypical radiologic signs and negative smears. Thus, the failures were not just the result of inattention to obvious signs and symptoms. Unfortunately, because the symptoms of active tuberculosis are nonspecific, early identification protocols are likely to identify a sizeable percentage of people who do not actually have the disease. Isolation of these people results in an expensive, unnecessary use of isolation rooms. For example, one study in a high-prevalence hospital found that for every eight patients isolated, only one had confirmed tuberculosis (Bock et al., 1996). Later, as tuberculosis case rates dropped, this ratio increased to 10 to 1 (Blumberg, 1999). In low-prevalence areas, the ratio may be as high as 100 to 1 (Scott et al., 1994). Researchers and clinicians have attempted to develop more precise diagnostic criteria and decision-support tools to allow quicker and more accurate identification of people with tuberculosis (Scott et al., 1994; Bock et al., 1996; Knirsch et al., 1998). This would promote earlier isolation and treatment. It would also help conserve resources by reducing the number of people incorrectly identified and isolated (false positives). Typically, however, such adjustments in prediction rules or decision criteria will result in more missed cases of active, potentially infectious disease (false negatives). For example, in one study, the use of prediction rules that were developed to reduce overisolation of nontuberculosis patients would have reduced the number of such patients with false-positive results from 253 to 95, but it would have missed 8 of 42 patients with (those with true disease) false negative results (Bock et al., 1996). In addition to increasing the costs of care, overisolation may be emotionally stressful for patients. It typically reduces an individual’s contact
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Tuberculosis in the Workplace with family and friends and often limits contacts with health care workers. People may also feel stigmatized by the apparatus of isolation including the warning signs outside rooms and the requirement that patients be masked during transport outside the isolation room.14 Treatment of Active Tuberculosis Treatment Regimens The discovery in 1946 that streptomycin was effective against active tuberculosis began the transformation of the disease from an often lethal illness to one that could almost always be effectively treated (Daniel, 1997). Six years later, a much more effective drug, isoniazid, came on the market, and in 1970, rifampin, another very effective drug, became available. The use of these two drugs in combination made short-course therapy possible, reducing the length of treatment from 18 months to 6 to 9 months for drug-sensitive strains. As noted earlier, treatment of active tuberculosis cuts death rates from 50 percent or more to near zero for immunocompetent people who have drug-sensitive disease and who receive timely, appropriate care. Unfortunately, multidrug-resistant strains of tuberculosis are much more difficult to treat, especially for patients with poorly functioning immune systems. Treatment of multidrug-resistant disease may require major surgery (e.g., removal of all or part of a lung) and long hospital stays. Patients may also undergo trials of treatment with second-line drug combinations that often must be used for long periods. These drugs also tend to produce more side effects than first-line drugs. Even with treatment, death rates among those with multidrug-resistant tuberculosis and immunosuppression may range from 40 to over 90 percent (CDC, 1994a). Drug therapy regimens differ depending on the type of tuberculosis, the likelihood or identification of multidrug-resistant disease, the presence of other medical conditions such as HIV infection or AIDS, patient age, risk of patient nonaderence to the regimen, and treatment side effects. For drug-sensitive disease, the most common treatment regimen first uses a combination of four drugs (izoniazid, rifampin, pyrazinamide, and ethambutol) for 2 months followed by treatment with two drugs (izoniazid and rifampin) for 4 months (Fujiwara et al., 2000). Some drug schedules call for daily doses of medication; others call for twice-weekly 14 Isolation for infectious tuberculosis does not require hospitalization if the person is not otherwise in need of inpatient care. Those isolated at home are instructed to stay at home without visitors. Home isolation may require that children and other high-risk individuals live elsewhere until the person with tuberculosis is no longer infectious. For those living in congregate settings such as nursing homes or prisons, however, protection of others may require use of properly functioning negative-pressure isolation rooms.
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Tuberculosis in the Workplace doses. Directly observed treatment is uniformly recommended for those on the latter schedule, which is often prescribed for those at high-risk of nonadherence. Although the full course of treatment must be completed to cure the disease and limit the development of drug resistance, most individuals with active, drug-susceptible tuberculosis usually become noninfectious within 1 or 2 months of the start of treatment. Those with drug-resistant disease may remain infectious for much longer. People are considered no longer infectious when they meet three conditions: (1) they are receiving adequate therapy, (2) they have a significant clinical response to therapy, and (3) they have three consecutive negative sputum smear results for sputum collected on different days. Directly Observed Therapy As noted in Chapter 1, the strategy of short-course, directly observed therapy is targeted at the prevention of drug-resistant tuberculosis arising from incomplete treatment. The earliest use of directly observed therapy in the United States dates to the 1970s, but concerns about civil rights slowed its acceptance and use (Mangura and Galanowsky, 2000). CDC recommended the strategy in 1992 (CDC, 1992c), and it is a central component of the tuberculosis control initiatives of the World Health Organization (WHO, 2000a). The recent IOM report on the elimination of tuberculosis in the United States recommended that “all states have health regulations that mandate completion of therapy (treatment to cure) for all patients with active tuberculosis” (IOM, 2000, p. 6). For individuals not living in prisons, nursing homes, or similar settings, directly observed treatment may involve scheduled appointments that bring a patient to a physician’s office, clinic, or other site so that a nurse or other trained individual can watch the person take the required medications. In some cases, outreach workers may travel to an individual’s residence. For health care and other workers, therapy may be observed in the employee health clinic. Even when directly observed therapy is prescribed, it does not guarantee full and complete therapy. Enhancements to the basic strategy (such as multidisciplinary case management teams or the addition of economic and other incentives) can significantly improve the results of therapy (IOM, 2000). CONCLUSION Today, tuberculosis is a disease that can almost always be cured if it is diagnosed promptly and treated fully in people who have well-functioning immune systems and drug-sensitive disease. Recently, treatment
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Tuberculosis in the Workplace priorities in community and workplace tuberculosis control programs have expanded to include latent tuberculosis infection. Faster, more accurate tests for both latent infection and active disease would benefit efforts to prevent and control tuberculosis in both the workplace and the community. The next chapter reviews the statutory basis for the 1997 proposed OSHA rule on occupational tuberculosis. Chapter 4 compares the proposed rule with the 1994 CDC guidelines to prevent transmission of tuberculosis in health care facilities.
Representative terms from entire chapter: