In the absence of an effective vaccine, prompt diagnosis and therapy are the keys to wiping out this disease.
TB IN THE UNITED STATES
In the United States, cases of active TB declined steadily from about 1920 through the mid 1980s. This decline was caused by improved living conditions and advances in public health in the early years of the century, as well as by the introduction of antitubercular medications (beginning with streptomycin sulfate, para-aminosalicylic acid, and isoniazid) in the late 1940s and early 1950s. By 1985, cases of TB in the United States had reached historically low levels, with the incidence of active TB in this country at roughly 9 cases per 100,000 people. With TB cases at record lows, the Centers for Disease Control and Prevention (CDC) set a goal of eliminating TB in the United States by the year 2000.
In the late 1980s, however, cases of TB in the United States began to climb again and continued to rise through the early 1990s. The causes of this increase include the dismantling of the public health infrastructure in the United States, with the closing of many TB clinics and free medication programs; the deterioration in living conditions among people in the inner cities, with many people spending time in overcrowded homeless shelters and prisons where TB can spread easily from one person to the next; the AIDS epidemic, which also allowed TB to spread rapidly among vulnerable populations; and, finally, continuing immigration to this country from areas where TB is endemic.
In response to the sharp increase in TB cases in the United States, a massive effort was made by public health authorities across the country. Largely through the institution of programs of directly observed therapy (DOT) in cities where the TB epidemic was most fierce, such as New York, there has been a steep decline in TB case rates in this country during the past 5 years.3 Last year, there were roughly 21,000 new cases of TB, with a record low incidence of about 8.5 cases per 100,000 people. As the US TB epidemic has receded somewhat, interest in strategies that might help prevent yet another increase in active cases has grown. Among these preventive strategies are the targeted screening of people with latent TB infection and the provision of preventive isoniazid therapy.
In the majority of cases, M tuberculosis is spread from person to person by the airborne route. As respiratory droplet nuclei that contain TB organisms are quite small (>5 æm) and cannot travel very far, transmission of mycobacteria usually requires fairly prolonged and close contact with an infectious case of TB. Once a person inhales the tubercle bacillus, the organism lodges in the lungs and is generally contained by the immune system. The mycobacteria in the lung will then usually remain dormant for many years, and the infected person will have no symptoms or signs of TB. Chest roentgenograms will also be normal, and the only indication of exposure to TB will be a positive tuberculin skin test. At this stage, a person is considered to have latent TB (criteria for determining a positive tuberculin skin test and for making a diagnosis of latent infection are listed in Table 1, page 68).
As previously noted, latent infection is found in nearly one third of the world’s population, with most of these infections occurring in residents of developing nations. The prevalence of infection in the United States varies greatly by country of birth, place of residence, and socioeconomic status. Among people of lower socioeconomic status or those who have recently immigrated here from countries where TB is very common, the prevalence of latent infection can range from 30 percent to 5004 In contrast, in many areas of the United States-particularly in middle class and upper middle class populations-the prevalence of latent infection is less than 1 percent. The prevalence of latent TB infection in a population is a key variable in targeting populations for TB screening and prevention. Most people with latent TB infection never develop any clinical illness. In a relatively small number of cases, however, the latent organisms residing in the lung will begin to multiply and cause a fever, cough, weight loss, and abnormal chest roentgenograms (typically, a cavitary infiltrate in the upper lung zones) that signal active TB. Patients with active TB often have mycobacterial organisms visible on light-microscope examination (that is, a positive sputum smear), and M tuberculosis can be cultured from their sputum.
The lifetime risk of developing active TB in a person with latent TB is estimated at 5 percent to 10 percent;5 most of this risk occurs in the first few years following the acquisition of latent infection. Certain medical conditions associated with a weakened immune system increase an individual’s chance of developing active disease once he/she has been infected. These conditions include AIDS (most prominently) as well as advanced malignancy, malnutrition, treatment with potent immunosuppressive drugs, end-stage renal disease, and diabetes mellitus.
TARGETED SCREENING AND PREVENTION
It is clear that blanket screening of all people in the United States would be an inefficient and extremely costly approach to TB prevention. For one thing, more than half of US counties (mostly in the Great Plains states and Upper Midwest) reported no cases of TB in 1996, according to the CDC. It follows that the number of people with latent infection in these areas is so low as to make screening superfluous. Rather, the CDC has issued guidelines recommending screening in selected populations at the highest risk for TB infection and disease (Table 2, page 68).
A tuberculin skin test should only be administered by a person trained in its application, as a poorly performed test can lead to errors in interpretation. The most important points to remember in performing and interpreting a tuberculin skin test are that the 5 tuberculin units of purified protein derivative should be injected intradermally (usually in the volar forearm) and that the amount of induration (not simply redness or erythema) should be measured 48 to 72 hours later. If the test is positive, the patient should have a chest roentgenogram and should be questioned thoroughly regarding TB symptoms. If both symptoms and chest roentgenograms are negative, a diagnosis of latent TB infection can be made, and the patient should be evaluated as a candidate for preventive therapy.
CONTACTS AND RECENT CONVERTERS
As previously noted, the chance that a person will develop active TB is greatest in the first 1 to 2 years after latent infection has been established. For this reason, those who have recently become infected should receive high priority as candidates for preventive therapy. Close contacts of active cases of TB are identified through contact investigations, which should begin immediately after an infectious case of TB has been reported to the local health department. Most people with TB infection who have been identified through contact investigations should receive isoniazid preventive therapy regardless of age. Note that a ?5-mm induration is considered a positive tuberculin skin test in a close contact of an active case of TB.
Recent tuberculin skin test converters are defined as individuals with a positive skin test who are known to have had a negative skin test within the previous 2 years. In general, there is no need for healthy people to be subjected to repeated skin testing, but in certain high-risk individuals, annual or semiannual testing is warranted. These individuals include health care workers (such as RCPs) who may have repeated exposure to patients with active TB.6 For these workers, testing as often as every 3 to 6 months may be appropriate7; any person with a newly positive tuberculin skin test should be evaluated carefully for active TB. If active TB is not present, preventive therapy should be offered-again, regardless of the patient’s age.
EMIGRATION FROM ENDEMIC AREAS
In some published studies of the prevalence of latent TB infection in recent immigrants to the United States from developing areas such as Tibet or Vietnam, 70 percent to 100 percent of those tested were positive.8,9 Therefore, routine screening of people who have recently arrived from high-prevalence countries or regions is warranted, and isoniazid preventive therapy should be prescribed for those with latent infection.
A question often arises about the interpretation of the tuberculin skin test in people who have previously been vaccinated with bacille Calmette-Guerin (BCG), which-despite considerable debate about its effectiveness in preventing TB-is widely administered in developing countries. It had long been thought that prior BCG vaccination would result in a lifelong false-positive tuberculin skin test result.
Several recent studies, however, indicate that the immunity (and the positive skin test) conferred by BCG given in infancy wanes by the time a person is 10 to 15 years old. A positive tuberculin skin test in an adult who received BCG in infancy is more likely to represent true infection with M tuberculosis than to reflect prior BCG vaccination.10 The CDC and American Thoracic Society therefore recommend that a history of BCG vaccination in childhood be ignored in interpreting a tuberculin skin test performed in adulthood.11
Once patients with HIV/AIDS have been infected with M tuberculosis, they are at very high risk for developing active disease, with incidence rates of 10 percent a year (as opposed to the 10 percent lifetime risk in immunocompetent people).12 For this reason, patients with HIV/AIDS should be screened for TB infection on a regular basis, and receive preventive therapy when latent TB infection is diagnosed, regardless of their age. Despite the immunocompromise associated with HIV, isoniazid preventive therapy has been shown to be extremely effective in this patient population.
Two aspects of TB screening in HIV-positive people deserve special attention. First, a greater than or equal to 5-mm induration is considered a positive tuberculin skin test in such patients.13 Second, because of the immunocompromise that is the hallmark of HIV infection, it is possible that a tuberculin skin test may be falsely negative in an AIDS patient with a low CD4 cell count. For this reason, some investigators previously advocated that AIDS patients with a negative tuberculin skin test be further evaluated for anergy (lack of skin-test response to common antigens such as mumps or tetanus). If found to be anergic, they would then be considered for isoniazid preventive therapy. Recent studies14,15 of anergic, HIV-positive injection drug users in urban centers such as New York and San Francisco, however, suggest that the risk of TB in this population is actually quite small. As a result, the CDC recommends that anergy testing not be included in the routine evaluation of tuberculin skin test results in HIV-infected people.16 Rather, the tuberculin skin test should be interpreted as in any other patient (with the exception of the greater than or equal to 5-mm induration being indicative of a positive result).
COMPLETION OF THERAPY
Making a diagnosis of TB infection, even in a patient at high risk for developing active disease, will not prevent a single case of TB unless a course of 6 to 12 months of isoniazid preventive therapy is completed by the patient. Unfortunately, experience shows that as few as 50 percent of patients who begin a course of preventive therapy will complete it.17 Although DOT programs have been immensely successful for active TB disease, preventive DOT programs are not in widespread use. This places an additional burden on physicians to educate patients about the need for preventive therapy and the importance of completing treatment once it has been started. Although isoniazid preventive therapy is extremely safe in most circumstances, patients should be counseled regarding side effects and the avoidance of alcohol. Patients should receive only 1 month’s supply of medication at a time, should be seen by a physician or experienced nurse regularly during treatment, and should seek medical attention promptly if side effects occur.
In the absence of an effective TB vaccine, the best way to reduce this disease in the United States and elsewhere is prompt diagnosis and institution of therapy for all active cases; thereby, it is possible to reduce the spread of the disease and lower the number of people who will develop latent infection (and the number who will then go on to develop active disease). Targeted TB screening and prevention programs, if properly applied, will also play a significant role in reducing the TB caseload in the United States.
Neil W. Schluger, MD, is director of the chest clinic at Bellevue Hospital Center, New York, and associate professor of medicine at New York University School of Medicine.
- Raviglione MC, Snider DE Jr, Kochi A. Global epidemiology of TB. Morbidity and mortality of a worldwide epidemic. JAMA. 1995;273:220-226.
- World Health Organization. The WHO/IUATLD Global Project on Anti-TB Drug Resistance Surveillance. Anti-TB Drug Resistance in the World. Geneva: World Health Organization; 1997.
- Frieden TR, Fujiwara PI, Washko RM, Hamburg MA. Tuberculosis in New York City-turning the tide. N Engl J Med. 1995;333:229-233.
- Schluger NW, Huberman R, Wolinsky N, Dooley R, Rom WN, Holzman RS. Tuberculosis infection and disease among persons seeking social services in New York City. International Journal of Tuberculosis and Lung Disease. 1997;1:31-37.
- Israel HL, Hetherington HW, Ord JG. A study of tuberculosis among students of nursing. JAMA. 1991;117:461-473.
- Cookson ST, Jarvis WR. Prevention of nosocomial transmission of Mycobacterium tuberculosis. Infect Dis Clin North Am. 1997;11:385-409.
- Centers for Disease Control and Prevention Guidelines for preventing the transmission of Mycobacterium tuberculosis in health care facilities. MMWR Morb Mortal Wkly Rep. 1994;43:1-132.
- Nelson KR, Bui H, Samet JH. Screening in special populations: a “case study” of recent Vietnamese immigrants. Am J Med. 1997;102:435-440.
- Truong DH, Hedemark LL, Mickman JK, Mosher LB, Dietrich SE, Lowry PW. Tuberculosis among Tibetan immigrants from India and Nepal in Minnesota, 1992-1995. Jama. 1997;277:735-738.
- Kroger L, Katila ML, Korppi M, Pietikainen M. Skin test reactivity to atypical mycobacteria among healthy Finnish preschool children vaccinated with BCG vaccine at birth. Acta Paediatr. 1992;81:891-895.
- Bass JB Jr, Farer LS, Hopewell PC, et al. Treatment of TB and TB infection in adults and children. Am J Respir Crit Care Med. 1994;149:1359-1374.
- Selwyn PA, Hartel D, Lewis VA, et al. A prospective study of the risk of TB among intravenous drug users with human immunodeficiency virus infection. N Engl J Med. 1989;320:545-550.
- Markowitz N, Hansen NI, Hopewell PC, et al. Incidence of TB in the United States among HIV-infected persons. Ann Intern Med. 1997;126:123-132.
- Gordin FM, Matts JP, Miller C, et al. A controlled trial of isoniazid in persons with anergy and human immunodeficiency virus infection who are at high risk for TB. N Engl J Med. 1997;337:315-320.
- Daley CL, Hahn JA, Moss AR, Hopewell PC, Schecter GF. Incidence of TB in injection drug users in San Francisco: impact of anergy. Am J Respir Crit Care Med. 1998;157:19-22.
- Centers for Disease Control and Prevention. Anergy skin testing and preventive therapy for HIV-infected persons: revised recommendations. MMWR Morb Mortal Wkly Rep. 1997;46:1-10.
- Camins BC, Bock N, Watkins DL, Blumberg HM. Acceptance of isoniazid preventive therapy by health care workers after tuberculin skin test conversion. Jama. 1996;275:1013-1015.
- Centers for Disease Control and Prevention. Screening for TB and TB infection in high-risk populations. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Morb Mortal Wkly Rep. 1995;44:19-34.