Correspondence

Management of Tuberculosis

N Engl J Med 2001; 345:1501-1502November 15, 2001

Article

To the Editor:

When discussing indications for the treatment of latent tuberculosis infection, Small and Fujiwara (July 19 issue)1 follow the joint statement of the American Thoracic Society and the Centers for Disease Control and Prevention (CDC)2 in considering patients regardless of age. Prior guidelines did not recommend routine treatment for those older than 35 years, the point at which isoniazid hepatotoxicity was thought to be more likely to occur than disease reactivation.3 Is age no longer a concern? For example, since treatment is now recommended for all tuberculin-positive persons who have emigrated from high-prevalence areas to the United States within the preceding five years, should we prescribe isoniazid to a recently arrived 75-year-old person? Should we withhold therapy from a 26-year-old who came to the United States at the age of 19?

Small and Fujiwara also recommend initial two-step testing for persons who are likely to have serial tuberculin tests, to avoid confusion from future false positive “conversions” caused by the booster phenomenon. As they note, such results imply waning immunity from infections acquired in the distant past. Yet the CDC recommends that all newly employed health care workers receive two-step testing if they lack proof that they have had a negative skin test within the preceding 12 months,4 despite the added expense and inconvenience. Is this step required for low-risk employees? What if one had a negative skin test two or three years previously? Would a 25-year-old employee who had been born in a high-prevalence area even require two-step testing, since the booster phenomenon is rare at this age?

Steven Leiner, N.P., P.A.-C.
Mission Neighborhood Health Center, San Francisco, CA 94110
sleiner@itsa.ucsf.edu

4 References

1
Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001;345:189-200
Full Text | Web of Science | Medline

2
Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Morb Mortal Wkly Rep 2000;49:1-51
Medline

3
Bass JB Jr, Farer LS, Hopewell PC, et al. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994;149:1359-1374
Web of Science | Medline

4
Guidelines for preventing the transmission of Mycobacterium tuberculosis in health care facilities, 1994. MMWR Morb Mortal Wkly Rep 1994;43:1-132
Medline

To the Editor:

Small and Fujiwara mention the possibility of eliminating tuberculosis in the United States. For this to become a reality, however, “hot spots” of tuberculosis, especially in the South and in urban areas, will need to be addressed by public health officials. Nearly all southeastern states continue to have rates of tuberculosis that are higher than the national average, with most cases occurring among U.S.-born persons, most frequently blacks.1,2 In Georgia, the number of cases of tuberculosis has increased in the past two years.1 The rates of disease in some areas of Atlanta exceed 100 cases per 100,000 persons per year,3 similar to the rates in developing countries.

The racial disparity is also striking, with rates that are 12 times as high among blacks as among whites. This high burden of disease greatly affects Grady Memorial Hospital, where active tuberculosis was diagnosed in 139 patients (a third of whom were coinfected with the human immunodeficiency virus) in 2000, for a rate of 496 cases per 100,000 admissions (Table 1Table 1Cases of Tuberculosis Reported in the United States, Georgia, and Grady Memorial Hospital in Atlanta.). During the past decade, if Grady Memorial Hospital had been a state, it would have ranked 28th in the country in terms of the number of cases reported.3 Tuberculosis is not a Medicaid-eligible disease in Georgia (as it is in all of the other high-incidence states); thus, the hospital has annually provided more than $1.5 million of uncompensated care to patients with tuberculosis.

Adequate resources for care, public health control, and research on interventions to interrupt the transmission of Mycobacterium tuberculosis in hot spots are much needed and will be required if we are serious about eliminating tuberculosis in the United States.

Henry M. Blumberg, M.D.
Carlos del Rio, M.D.
Emory University School of Medicine, Atlanta, GA 30303
hblumbe@emory.edu

3 References

1
Reported tuberculosis in the United States, 2000. Atlanta: Centers for Disease Control and Prevention, June 2001.

2
Talbot EA, Moore M, McCray E, Binkin NJ. Tuberculosis among foreign-born persons in the United States, 1993-1998. JAMA 2000;284:2894-2900
CrossRef | Web of Science | Medline

3
Sotir MJ, Parrott P, Metchock B, et al. Tuberculosis in the inner city: impact of a continuing epidemic in the 1990s. Clin Infect Dis 1999;29:1138-1144
CrossRef | Web of Science | Medline

To the Editor:

In their otherwise excellent review of tuberculosis, Small and Fujiwara did not adequately address the difficult subject of the use of rifampin with nonnucleoside reverse-transcriptase inhibitors. There is no change in rifampin levels when it is given with either of the two most commonly prescribed nonnucleoside reverse-transcriptase inhibitors, nevirapine and efavirenz.1,2 Small and Fujiwara appropriately note that delavirdine and nevirapine, the first two of these agents to be approved by the Food and Drug Administration, are not recommended for use with rifampin because rifampin can significantly lower serum levels of these antiretroviral agents. However, rifampin reduces the area under the curve, minimal concentration, and maximal concentration of efavirenz, the most recently approved nonnucleoside reverse-transcriptase inhibitor, by less than 30 percent in all studies published to date.2,3 Hence, many experts recommend the combination of rifampin and efavirenz, with an increase in the dose of efavirenz to 800 mg per day, for the treatment of patients with tuberculosis who require antiretroviral therapy.2,3 One small study even compared a regimen of efavirenz and rifampin with a regimen of rifampin alone and found that both regimens were highly efficacious.4

Lori E. Fantry, M.D., M.P.H.
University of Maryland Medical School, Baltimore, MD 21201
lfantry@medicine.umaryland.edu

4 References

1
Robinson P, Lamson M, Gigliotti M, Myers M. Pharmacokinetic (PK) interaction between nevirapine (NVP) and rifampin (RMP). In: Conference record of the 12th World AIDS Conference, June 28–July 3, 1998. Geneva: Marathon Multimedia, 1998:1115. abstract.

2
Benedek I, Joshi A, Fiske WD, et al. Pharmacokinetic interaction between efavirenz (EFV) and rifampin (RIF) in healthy volunteers. In: Conference record of the 12th World AIDS Conference, June 28–July 3, 1998. Geneva: Marathon Multimedia, 1998:829. abstract.

3
Lopez-Cortes LF, Ruiz R, Viciana P, et al. Pharmacokinetic interactions between rifampin and efavirenz in patients with tuberculosis and HIV infection. In: Programs and abstracts of the Eighth Conference on Retroviruses and Opportunistic Infections, February 4–8, 2001. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2001:52. abstract.

4
Hung C-C, Chen M-Y, Hsieh S-M, et al. Efficacy of highly active antiretroviral therapy (HAART) combined with rifamycins-containing anti-tuberculosis (anti-TB) therapy in HIV-1 infected patients with tuberculosis (TB). In: Programs and abstracts of the Eighth Conference on Retroviruses and Opportunistic Infections, February 4–8, 2001. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2001:208. abstract.

To the Editor:

Small and Fujiwara state that evaluation of urine for discoloration can be used to assess compliance in patients who are taking rifampin for tuberculosis. Because of its pharmacokinetics, isoniazid is also suitable for use in an assessment of compliance. The “Arkansas method” for the detection of isoniazid allows compliance to be assessed even if patients took the drug up to 24 hours before their arrival at the clinic.1,2 The peak of the rifampin-induced orange coloration of the urine occurs six hours after the ingestion of the drug. This test lacks specificity and sensitivity if it is performed more than 12 hours after the ingestion of rifampin.3 The Arkansas method has equally good results with the use of commercially available paper strips (Taxo INH test strips, Becton Dickinson, Cowley, United Kingdom) or dipsticks made in any laboratory.4

P.E. Meissner, M.D.
J.B.S. Coulter, M.D.
Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom
peter.meissner@urz.uni-heidelberg.de

4 References

1
Elizaga J, Friedland JS. Monitoring compliance with antituberculous treatment by detection of isoniazid in urine. Lancet 1997;350:1225-1226
CrossRef | Web of Science | Medline

2
Schraufnagel DE, Stoner R, Whiting E, Snukst-Torbeck G, Werhane MJ. Testing for isoniazid: an evaluation of the Arkansas method. Chest 1990;98:314-316
CrossRef | Web of Science | Medline

3
Burkhardt KR, Nel EE. Monitoring regularity of drug intake in tuberculous patients by means of simple urine tests. S Afr Med J 1980;57:981-985
Medline

4
Kilburn JO, Beam RE, David HL, Sanchez E, Corpe RF, Dunn W. Reagent-impregnated paper strip for detection of metabolic products of isoniazid in urine. Am Rev Respir Dis 1972;106:923-924
Web of Science | Medline

Author/Editor Response

Dr. Small replies:

To the Editor: I appreciate the valid comments made by each of the correspondents, the spectrum of which emphasizes the complexities of managing tuberculosis in the current era. Some of this complexity arises from the intrinsic challenges of translating treatment guidelines into clinical practice. For example, Mr. Leiner asks whether, given the de-emphasis of age as a criterion for treating latent tuberculosis infection, I would “prescribe isoniazid to a recently arrived 75-year-old” immigrant. Perhaps, depending on the details. In general, I might not, but I certainly would if the person were at high risk for progression to active disease (such persons are a group for which there has never been an age cutoff).

An important resource for assistance in working through the details of specific situations is the “tuberculosis warmlines” funded in part by the CDC (415-502-4700 or 800-4TB-DOCS). Health care providers who dial these numbers will be connected within 24 hours to a tuberculosis expert with whom they may discuss individual situations.

Peter M. Small, M.D.
Stanford University Medical Center, Stanford, CA 94305
peter@molepi.stanford.edu