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The Use of Preventive Therapy for Tuberculous Infection in the United States Recommendations of the Advisory Committee for Elimination of Tuberculosis
The appropriate use of preventive therapy will play a crucial role in efforts to eliminate tuberculosis in the United States by the year 2010 (1). When taken as prescribed, isoniazid preventive therapy is highly effective in preventing latent tuberculous infection from progressing to clinically apparent disease. In controlled trials conducted by the Public Health Service in ordinary clinical and public health settings, isoniazid preventive therapy reduced the incidence of disease by 54%-88% (2). The main reason for the variation in efficacy appears to have been the amount of medication actually taken during the year in which isoniazid was prescribed. In a trial conducted in eastern Europe among infected adults with abnormal chest radiographs, a 12-month course of isoniazid preventive therapy was 75% effective among all persons assigned to the regimen and 93% effective among those who were compliant with therapy (3). Similarly, isoniazid preventive therapy was estimated to be 98% effective among children in Houston and in recently infected nursing home patients who were compliant with therapy (4,5). Isoniazid preventive therapy has been shown to be effective for long periods and to be reasonably cost-effective (6,7).
Despite its proven effectiveness, preventive therapy is less widely applied in the United States than it should be. Reports submitted to CDC by tuberculosis control programs in states and large cities indicate that less than 60% of infected contacts of persons with newly diagnosed tuberculosis are being started on preventive therapy (CDC, unpublished data). In a study to determine why tuberculosis is not prevented, investigators found that in a high proportion of newly diagnosed cases the opportunity to prevent disease had been missed (8). Although three-fourths of the persons surveyed had contact with a health-care provider within the 5 years before the most recent diagnosis of tuberculosis, less than one-third of them had been tuberculin skin tested even though many had risk factors for tuberculosis. Of the persons who had positive skin tests and other factors placing them at increased risk of disease, only 5% had been offered preventive therapy.
The following recommendations of the Advisory Committee for Elimination of Tuberculosis (ACET) are intended to increase the effective application of preventive therapy in the United States. Health departments, medical and nursing schools, schools of public health, voluntary agencies, and professional societies may use these guidelines to educate health-care providers about the appropriate use of preventive therapy in efforts to eliminate tuberculosis. The ACET recognizes that clinical decisions regarding preventive therapy must be individualized and based on an assessment of benefits and risks. These recommendations are intended to assist physicians and patients in making these decisions. RECOMMENDATIONS
The main purpose of preventive therapy is to prevent latent (asymptomatic) infection from progressing to clinical disease (9). Such therapy also is used to prevent initial infection and to prevent recurrence of past disease.
Although the number of persons in the United States who are asymptomatically infected with Mycobacterium tuberculosis is not known, projections based on previous data range from 10 million to 15 million (CDC, unpublished data). Estimates are that greater than 90% of current tuberculosis cases occur from this large pool of previously infected persons. Unless preventive therapy is more effectively applied to reduce this reservoir of infection, hundreds of thousands of new tuberculosis cases and tens of thousands of deaths can be expected over the next few decades. High-Risk Groups
Certain groups within the infected population are at greater risk than others and should receive high priority for preventive therapy. In the United States, persons with any of the following six risk factors should be considered candidates for preventive therapy, regardless of age, if they have not previously been treated:
Persons with human immunodeficiency virus (HIV) infection (greater than or equal to 5 mm)* and persons with risk factors for HIV infection whose HIV infection status is unknown but who are suspected of having HIV infection.
Close contacts of persons with newly diagnosed infectious tuberculosis (greater than or equal to 5 mm). In addition, tuberculin-negative ( less than 5 mm) children and adolescents who have been close contacts of infectious persons within the past 3 months are candidates for preventive therapy until a repeat tuberculin skin test is done 12 weeks after contact with the infectious source.
Recent converters, as indicated by a tuberculin skin test (greater than or equal to 10 mm increase within a 2-year period for those less than 35 years old; greater than or equal to 15 mm increase for those greater than or equal to 35 years of age).
Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis (greater than or equal to 5 mm).
Intravenous drug users known to be HIV-seronegative (greater than or equal to 10 mm).
Persons with medical conditions that have been reported to increase the risk of tuberculosis (greater than or equal to 10 mm).
In addition, in the absence of any of the above risk factors, persons less than 35 years of age in the following high-incidence groups are appropriate candidates for preventive therapy if their reaction to a tuberculin skin test is greater than or equal to 10 mm:
Foreign-born persons from high-prevalence countries. Medically underserved low-income populations, including high-risk racial or ethnic minority populations, especially blacks, Hispanics, and Native Americans.
Residents of facilities for long-term care (e.g., correctional institutions, nursing homes, and mental institutions).
In addition to the groups listed above, public health officials should be alert for other high-risk populations in their communities. For example, through a review of cases reported in the community over several years, health officials may use geographic or sociodemographic factors to identify groups that should be targeted for intervention. Screening and preventive therapy programs should be initiated and promoted within these populations based on an analysis of cases and infection in the community. To the extent possible, members of high-risk groups and their health-care providers should be involved in the design, implementation, and evaluation of these programs. Staff of facilities in which an individual with disease would pose a risk to large numbers of susceptible persons (e.g., correctional institutions, nursing homes, mental institutions, other health-care facilities, schools, and child-care facilities) may also be considered for preventive therapy if their tuberculin reaction is greater than or equal to 10 mm induration. Preventive Therapy
The usual preventive therapy regimen is isoniazid (10 mg/kg daily for children, up to a maximum adult dose of 300 mg daily). The recommended duration of isoniazid preventive treatment varies from 6 to 12 months of continuous therapy (9). Twelve months of therapy is recommended for persons with HIV infection and persons with stable abnormal chest radiographs consistent with past tuberculosis. The other groups should receive a minimum of 6 continuous months of therapy.
To ensure that persons in high-risk groups comply with therapy, health-care personnel should, if necessary, directly observe the therapy. Isoniazid can be given twice weekly in a dose of 15 mg/kg (up to 900 mg) when therapy must be directly observed and resources are inadequate for daily therapy. Recommendations of the ACET are summarized in Table 1.
Patients should be thoroughly educated and should be monitored monthly, in person, by appropriately trained personnel. Isoniazid preventive therapy should not be prescribed if monthly monitoring cannot be done. Some data indicate that black and Hispanic women, especially postpartum, may be at greater risk of serious or fatal adverse reactions and, therefore, should be closely monitored (14-16). Reducing the risk of adverse reactions, even when this risk is low, is as important as providing the benefits of preventive therapy. Additional details on preventive therapy have been published (9).
the United States. MMWR 1989;38(suppl no. S-3):1-25.
2. Comstock GW, Woolpert SF. Preventive therapy. In: Kubica GP, Wayne LG, eds. The mycobacteria: a sourcebook. New York: Marcel Dekker, Inc, 1984:1071-82.
3. 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.
4. Hsu KH. Thirty years after isoniazid: its impact on tuberculosis in children and adolescents. JAMA 1984;251:1283-5.
5. Stead WW, To T, Harrison RW, Abraham JH. Benefit-risk considerations in preventive treatment for tuberculosis in elderly persons. Ann Intern Med 1987;107:843-5.
6. Comstock GW, Baum C, Snider DE. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the Bethel isoniazid studies. Am Rev Respir Dis 1979;119:827-30.
7. Rose DN, Schecter CB, Fahs MC, Silver AL. Tuberculosis prevention: cost-effectiveness analysis of isoniazid chemoprophylaxis. Am J Prev Med 1988;4:102-9.
8. Glassroth JB, Hopewell PC, Bailey WC, Harden J. Why tuberculosis is not prevented. Am Rev Respir Dis (in press).
9. American Thoracic Society/CDC. Treatment of tuberculosis and tuberculosis infection in adults and children. Am Rev Respir Dis 1986;134:355-63. 10. American Thoracic Society/CDC. Diagnostic standards and classification of tuberculosis. Am Rev Respir Dis (in press). 11. Narain R, Chandrasekhar P, Naganna K. A fresh look at the definition of tuberculous infection and new infection. Ind J Med Res 1976;64:336-57. 12. Stead WW, To T. The significance of the tuberculin skin test in elderly persons. Ann Intern Med 1987;107:837-42. 13. Bass JB, Sanders RV, Kirkpatrick MB. Choosing an appropriate cutting point for conversion in annual tuberculin skin testing. Am Rev Respir Dis 1985;132:379-81. 14. Kopanoff DE, Snider DE, Caras GJ. Isoniazid related hepatitis. Am Rev Respir Dis 1978;117:991-1001. 15. Franks AL, Binkin NJ, Snider DE, Rokaw WM, Becker S. Isoniazid hepatitis among pregnant and postpartum Hispanic patients. Public Health Rep 1989;104:151-5. 16. Moulding TS, Redeker AG, Kanel GC. Twenty isoniazid-associated deaths in one state. Am Rev Respir Dis 1989;140:700-5.
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