Priorities for the Treatment of Latent Tuberculosis
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《新英格兰医药杂志》
To the Editor: We agree with Horsburgh (May 13 issue)1 that the lifetime risk of active tuberculosis is helpful in deciding whether to treat latent tuberculosis infection.2,3 Attention to three problems addressed years ago2,3,4 would improve Horsburgh's analysis: the rate at which the risk of active tuberculosis falls with time2,3 was underestimated, discounting5 was ignored, and the risk of treatment2,3,4 was not incorporated into the analysis. A corrected analysis would reveal a substantially lower lifetime risk of active tuberculosis, especially among young persons and persons in risk groups with the highest rates of active tuberculosis, with the possible exception of persons infected with the human immunodeficiency virus (HIV). With appropriate discounting and attention to the toxicity of treatment, one could calculate the effect of treatment on the present value of quality-adjusted life-years gained (or perhaps lost). A corrected analysis that showed a lower lifetime risk of active tuberculosis and appropriately considered the risks of treatment would generate less enthusiasm for the treatment of many persons with latent tuberculosis infection.
William C. Taylor, M.D.
Beth Israel Deaconess Medical Center
Boston, MA 02215
Joel Tsevat, M.D., M.P.H.
University of Cincinnati Medical Center
Cincinnati, OH 45267
Stephen G. Pauker, M.D.
Tufts–New England Medical Center
Boston, MA 02111
References
Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004;350:2060-2067.
Taylor WC, Aronson MD, Delbanco TL. Should young adults with a positive tuberculin test take isoniazid? Ann Intern Med 1981;94:808-813.
Tsevat J, Taylor WC, Wong JB, Pauker SG. Isoniazid for the tuberculin reactor: take it or leave it. Am Rev Respir Dis 1988;137:215-220.
Comstock GW, Edwards PQ. The competing risks of tuberculosis and hepatitis for adult tuberculin reactors. Am Rev Respir Dis 1975;111:573-577.
Gold MR, Siegel JE, Russell LB, Weinstein MC, eds. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996.
To the Editor: Horsburgh concludes that targeting persons at high risk for reactivation tuberculosis could improve rates of treatment completion and help to eradicate tuberculosis in the United States. However, an important, but unstated, shortcoming of this conclusion is that a significant number of these high-risk patients are anergic. Moreover, a significant proportion of the disease burden of reactivation tuberculosis in these populations may be missed.
The percentage of anergic patients in whom reactivation tuberculosis will ultimately develop is unknown. However, among anergic patients, active tuberculosis develops at a rate at least equal to that among patients who have positive tuberculin skin tests with purified protein derivative (PPD). Moreno et al. found that among patients with HIV infection, the risk of tuberculosis was similar in those who were anergic and those who were PPD-positive (12.4 vs. 10.4 cases per 100 person-years).1 Similarly, Fang et al. found that anergic patients who were receiving hemodialysis had a risk of tuberculosis that was similar to the risk among PPD-positive patients (15 percent and 13.2 percent, respectively).2 Thus, although a positive tuberculin skin test mandates intensive efforts to ensure adherence to treatment, a negative test result warrants even greater vigilance.
Macarthur Charles, M.D., Ph.D.
Kyu Y. Rhee, M.D., Ph.D.
Weill Medical College of Cornell University
New York, NY 10021
kasav@lycos.com
References
Moreno S, Baraia-Etxaburu J, Bouza E, et al. Risk for developing tuberculosis among anergic patients infected with HIV. Ann Intern Med 1993;119:194-198.
Fang HC, Chou KJ, Chen CL, et al. Tuberculin skin test and anergy in dialysis patients of a tuberculosis-endemic area. Nephron 2002;91:682-687.
To the Editor: The estimation of the lifetime risk of reactivation of tuberculosis according to the size of the tuberculin skin test, age, and risk group provides a valuable aid to decision making in the treatment of latent tuberculosis infection. The studies used by Horsburgh to estimate the risk associated with positive skin tests were published more than 30 years ago and were conducted within a limited geographic area.
We measured the annual incidence of tuberculosis in a cohort of 15,489 comprising predominantly refugees from Southeast Asia who were 12 years of age or older and had chest x-rays on arrival that showed no abnormalities. Over an average follow-up period of 10 years, the annual risk of tuberculosis among subjects with tuberculin skin tests that were 15 mm or larger was 0.12 percent.1 This rate is the same as that in persons 36 years of age or older, and it is slightly lower than the rate in persons 15 to 35 years of age (0.19 percent) in Horsburgh's analysis. The inclusion of these more recent data from a region that is the source of many cases of tuberculosis in Western countries2 strengthens the generalizability of Horsburgh's conclusions on the lifetime risk of tuberculosis.
Guy B. Marks, Ph.D.
Woolcock Institute of Medical Research
Sydney, NSW 2050, Australia
Warwick J. Britton, Ph.D.
University of Sydney
Sydney, NSW 2006, Australia
References
Marks G, Bai J, Simpson SE, Sullivan EA, Stewart GJ. Incidence of tuberculosis among a cohort of tuberculin-positive refugees in Australia: reappraising the estimates of risk. Am J Respir Crit Care Med 2000;162:1851-1854.
Centers for Disease Control and Prevention. Trends in tuberculosis -- United States, 1998-2003. MMWR Morb Mortal Wkly Rep 2004;53:209-214.
Dr. Horsburgh replies: Drs. Charles and Rhee correctly observe that many persons with advanced HIV infection will be anergic, a condition that limits the usefulness of the tuberculin skin test for the diagnosis of latent tuberculosis in this population. However, after such patients begin antiretroviral therapy, the ability to respond to the test is restored; as soon as the CD4 count rises above 100 cells per cubic millimeter, the tuberculin skin test can be used to identify or rule out latent tuberculosis.1 Moreover, in the United States, rates of tuberculosis among anergic, "high-risk" persons have been found to be substantially lower than elsewhere,2 suggesting that a substantial proportion of the tuberculosis among anergic persons in the report by Moreno et al.,3 cited by Charles and Rhee, may be attributable to recent infection, not to reactivation.
Drs. Marks and Britton note that during a more recent period, the rate of reactivation tuberculosis in Australia was 0.12 percent per year. The median age of their cohort was 27 years; therefore, their results are quite similar to those I derived with the use of older data. This observation confirms that the rates calculated for my article are not likely to be substantial overestimates. Furthermore, it provides evidence that these rates are likely to pertain in other regions where the risk of reexposure to Mycobacterium tuberculosis is low.
In their analyses, Dr. Taylor and colleagues, citing a Danish study and a U.S. study, used rates of reactivation tuberculosis that were lower than the rates I used. However, the U.S. study that they cite4 has the lowest rate of the five published U.S. studies.5 Therefore, I used the median rate, a rate found in three of those five studies, rather than the lower rate.
The objective of my article was to provide more accurate information about the individual patient's risk of reactivation tuberculosis. This information will assist patients and clinicians in making decisions about undertaking treatment of latent tuberculosis. It should help in refining the national strategy for the elimination of tuberculosis. Therefore, I agree with Dr. Taylor and colleagues that it would be instructive to analyze the costs and benefits of treatment of latent tuberculosis in light of the revised lifetime risks that I calculated. However, such an analysis was beyond the scope of the present analysis.
C. Robert Horsburgh, Jr., M.D.
Boston University School of Public Health
Boston, MA 02118
rhorsbu@bu.edu
References
Fisk T, Hon H-M, Lennox JL, von Reyn CF, Horsburgh CR Jr. Detection of latent tuberculosis among HIV-infected patients after initiation of highly active antiretroviral therapy. AIDS 2003;17:1102-1104.
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 tuberculosis. N Engl J Med 1997;337:315-320.
Moreno S, Baraia-Etxaburu J, Bouza E, et al. Risk for developing tuberculosis among anergic patients infected with HIV. Ann Intern Med 1993;119:194-198.
Comstock GW, Woolpert SF, Livesay VT. Tuberculosis studies in Muscogee County, Georgia: twenty-year evaluation of a community trial of BCG vaccination. Public Health Rep 1976;91:276-280.
Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004;350:2060-2067.
William C. Taylor, M.D.
Beth Israel Deaconess Medical Center
Boston, MA 02215
Joel Tsevat, M.D., M.P.H.
University of Cincinnati Medical Center
Cincinnati, OH 45267
Stephen G. Pauker, M.D.
Tufts–New England Medical Center
Boston, MA 02111
References
Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004;350:2060-2067.
Taylor WC, Aronson MD, Delbanco TL. Should young adults with a positive tuberculin test take isoniazid? Ann Intern Med 1981;94:808-813.
Tsevat J, Taylor WC, Wong JB, Pauker SG. Isoniazid for the tuberculin reactor: take it or leave it. Am Rev Respir Dis 1988;137:215-220.
Comstock GW, Edwards PQ. The competing risks of tuberculosis and hepatitis for adult tuberculin reactors. Am Rev Respir Dis 1975;111:573-577.
Gold MR, Siegel JE, Russell LB, Weinstein MC, eds. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996.
To the Editor: Horsburgh concludes that targeting persons at high risk for reactivation tuberculosis could improve rates of treatment completion and help to eradicate tuberculosis in the United States. However, an important, but unstated, shortcoming of this conclusion is that a significant number of these high-risk patients are anergic. Moreover, a significant proportion of the disease burden of reactivation tuberculosis in these populations may be missed.
The percentage of anergic patients in whom reactivation tuberculosis will ultimately develop is unknown. However, among anergic patients, active tuberculosis develops at a rate at least equal to that among patients who have positive tuberculin skin tests with purified protein derivative (PPD). Moreno et al. found that among patients with HIV infection, the risk of tuberculosis was similar in those who were anergic and those who were PPD-positive (12.4 vs. 10.4 cases per 100 person-years).1 Similarly, Fang et al. found that anergic patients who were receiving hemodialysis had a risk of tuberculosis that was similar to the risk among PPD-positive patients (15 percent and 13.2 percent, respectively).2 Thus, although a positive tuberculin skin test mandates intensive efforts to ensure adherence to treatment, a negative test result warrants even greater vigilance.
Macarthur Charles, M.D., Ph.D.
Kyu Y. Rhee, M.D., Ph.D.
Weill Medical College of Cornell University
New York, NY 10021
kasav@lycos.com
References
Moreno S, Baraia-Etxaburu J, Bouza E, et al. Risk for developing tuberculosis among anergic patients infected with HIV. Ann Intern Med 1993;119:194-198.
Fang HC, Chou KJ, Chen CL, et al. Tuberculin skin test and anergy in dialysis patients of a tuberculosis-endemic area. Nephron 2002;91:682-687.
To the Editor: The estimation of the lifetime risk of reactivation of tuberculosis according to the size of the tuberculin skin test, age, and risk group provides a valuable aid to decision making in the treatment of latent tuberculosis infection. The studies used by Horsburgh to estimate the risk associated with positive skin tests were published more than 30 years ago and were conducted within a limited geographic area.
We measured the annual incidence of tuberculosis in a cohort of 15,489 comprising predominantly refugees from Southeast Asia who were 12 years of age or older and had chest x-rays on arrival that showed no abnormalities. Over an average follow-up period of 10 years, the annual risk of tuberculosis among subjects with tuberculin skin tests that were 15 mm or larger was 0.12 percent.1 This rate is the same as that in persons 36 years of age or older, and it is slightly lower than the rate in persons 15 to 35 years of age (0.19 percent) in Horsburgh's analysis. The inclusion of these more recent data from a region that is the source of many cases of tuberculosis in Western countries2 strengthens the generalizability of Horsburgh's conclusions on the lifetime risk of tuberculosis.
Guy B. Marks, Ph.D.
Woolcock Institute of Medical Research
Sydney, NSW 2050, Australia
Warwick J. Britton, Ph.D.
University of Sydney
Sydney, NSW 2006, Australia
References
Marks G, Bai J, Simpson SE, Sullivan EA, Stewart GJ. Incidence of tuberculosis among a cohort of tuberculin-positive refugees in Australia: reappraising the estimates of risk. Am J Respir Crit Care Med 2000;162:1851-1854.
Centers for Disease Control and Prevention. Trends in tuberculosis -- United States, 1998-2003. MMWR Morb Mortal Wkly Rep 2004;53:209-214.
Dr. Horsburgh replies: Drs. Charles and Rhee correctly observe that many persons with advanced HIV infection will be anergic, a condition that limits the usefulness of the tuberculin skin test for the diagnosis of latent tuberculosis in this population. However, after such patients begin antiretroviral therapy, the ability to respond to the test is restored; as soon as the CD4 count rises above 100 cells per cubic millimeter, the tuberculin skin test can be used to identify or rule out latent tuberculosis.1 Moreover, in the United States, rates of tuberculosis among anergic, "high-risk" persons have been found to be substantially lower than elsewhere,2 suggesting that a substantial proportion of the tuberculosis among anergic persons in the report by Moreno et al.,3 cited by Charles and Rhee, may be attributable to recent infection, not to reactivation.
Drs. Marks and Britton note that during a more recent period, the rate of reactivation tuberculosis in Australia was 0.12 percent per year. The median age of their cohort was 27 years; therefore, their results are quite similar to those I derived with the use of older data. This observation confirms that the rates calculated for my article are not likely to be substantial overestimates. Furthermore, it provides evidence that these rates are likely to pertain in other regions where the risk of reexposure to Mycobacterium tuberculosis is low.
In their analyses, Dr. Taylor and colleagues, citing a Danish study and a U.S. study, used rates of reactivation tuberculosis that were lower than the rates I used. However, the U.S. study that they cite4 has the lowest rate of the five published U.S. studies.5 Therefore, I used the median rate, a rate found in three of those five studies, rather than the lower rate.
The objective of my article was to provide more accurate information about the individual patient's risk of reactivation tuberculosis. This information will assist patients and clinicians in making decisions about undertaking treatment of latent tuberculosis. It should help in refining the national strategy for the elimination of tuberculosis. Therefore, I agree with Dr. Taylor and colleagues that it would be instructive to analyze the costs and benefits of treatment of latent tuberculosis in light of the revised lifetime risks that I calculated. However, such an analysis was beyond the scope of the present analysis.
C. Robert Horsburgh, Jr., M.D.
Boston University School of Public Health
Boston, MA 02118
rhorsbu@bu.edu
References
Fisk T, Hon H-M, Lennox JL, von Reyn CF, Horsburgh CR Jr. Detection of latent tuberculosis among HIV-infected patients after initiation of highly active antiretroviral therapy. AIDS 2003;17:1102-1104.
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 tuberculosis. N Engl J Med 1997;337:315-320.
Moreno S, Baraia-Etxaburu J, Bouza E, et al. Risk for developing tuberculosis among anergic patients infected with HIV. Ann Intern Med 1993;119:194-198.
Comstock GW, Woolpert SF, Livesay VT. Tuberculosis studies in Muscogee County, Georgia: twenty-year evaluation of a community trial of BCG vaccination. Public Health Rep 1976;91:276-280.
Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004;350:2060-2067.