Correspondence
Treatment of Latent Tuberculosis Infection
N Engl J Med 2003; 348:1292-1293March 27, 2003
- Article
To the Editor:
I was perturbed by the recommendation of Jasmer et al. (Dec. 5 issue)1 that an asymptomatic, low risk, 27-year-old schoolteacher with a 17-mm induration on intradermal tuberculin skin test “should not be treated.” The authors state, “One cannot conclude that she has had recent tuberculin conversion, because she has not had a negative tuberculin test within the past two years.” In fact, one might take the opposite tack and state that one cannot conclude that she did not have a tuberculin conversion during the previous two years in the absence of a prior negative tuberculin test. The Centers for Disease Control and Prevention recommend that “persons with no known risk factors for tuberculosis may be considered for treatment of LTBI [latent tuberculosis infection] if their reaction to tuberculin skin test is ≥15 mm.”2 One might view this person as being in an intermediate-risk group, since she is in a setting in which she would expose and potentially infect many children and adolescents should she become symptomatic. The authors themselves quote the statement by the Institute of Medicine that “`efforts to prevent cases [of tuberculosis] from occurring must be amplified.'” Neither financial constraints nor the risk of hepatotoxic effects of isoniazid (a risk that has recently been markedly reduced) should prevent the use of a chemotherapeutic agent whose efficacy has been documented for over 30 years.
2 ReferencesLeslie L. Barton, M.D.
University of Arizona School of Medicine, Tucson, AZ 85724-5073
llb@peds.arizona. edu 1
Jasmer RM ,Nahid P ,Hopewell PC . Latent tuberculosis infection. N Engl J Med 2002;347:1860-1866
Full Text | Web of Science | Medline2
Core curriculum on tuberculosis: what the clinician should know. 4th ed. Atlanta: Centers for Disease Control and Prevention, 2000.
To the Editor:
Jasmer et al. did not mention the administration of isoniazid and rifampin for three months as a choice of treatment. Daily treatment for three months with isoniazid and rifampin has been shown to be highly effective in adults1 and children2 who are not infected with the human immunodeficiency virus (HIV). In the United Kingdom, this regimen is currently recommended for the treatment of latent tuberculosis in both adults and children.3 In addition, three-month regimens of isoniazid and rifampin provided protection against active tuberculosis that was equivalent to the protection provided by a six-month regimen of isoniazid alone or a three-month regimen of isoniazid, rifampin, and pyrazinamide in HIV-positive Ugandan adults.4
4 ReferencesPhilippe Lepage, M.D., Ph.D.
University of Liege, 4000 Liege, Belgium
philippe.lepage@chrcitadelle. be 1
Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council
CrossRef | Web of Science | Medline2
Ormerod LP . Rifampicin and isoniazid prophylactic chemotherapy for tuberculosis. Arch Dis Child 1998;78:169-171
CrossRef | Web of Science | Medline3
Joint Tuberculosis Committee of the British Thoracic Society
CrossRef | Web of Science | Medline4
Whalen CC ,Johnson JL ,Okwera A , et al. A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. N Engl J Med 1997;337:801-808
Full Text | Web of Science | Medline
To the Editor:
The excellent clinical review of latent Mycobacterium tuberculosis infection by Jasmer and coworkers fails to mention, or include in Table 1 of the article, patients treated with anti–tumor-necrosis factor (TNF) monoclonal antibodies, such as infliximab (Remicade). In a recent report in the Journal, 1 70 cases of reactivation tuberculosis were reported among 147,000 patients worldwide who were treated with infliximab for rheumatoid arthritis or Crohn's disease. More than 40 percent of these patients had extrapulmonary or disseminated tuberculosis. Every effort should be made to rule out latent tuberculosis infection and to administer prophylaxis before providing treatment with infliximab.
1 ReferencesFrancesco G. De Rosa, M.D.
University of Turin, 10149 Turin, Italy
francescogiuseppe.derosa@unito. it Donald E. Craven, M.D.
Lahey Clinic, Burlington, MA 018031
Keane J ,Gershon S ,Wise RP , et al. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N Engl J Med 2001;345:1098-1104
Full Text | Web of Science | Medline
To the Editor:
The authors state that Patient 2 (a 27-year-old schoolteacher born in the United States) was at low risk for tuberculosis infection and should not have undergone testing with purified protein derivative. In Hawaii, the Department of Education requires all teachers to undergo such testing at the time of initial employment. My experience suggests that other states have similar policies. The implied rationale is to identify teachers who might transmit tuberculosis to their students. Do the authors recommend that such programs be discontinued?
Bernard C. Meyer, M.D.
Kaiser Permanente, Hawaii, Makawao, HI 96768
hanablue@gte.net Author/Editor Response
Barton and Meyer question our decision not to treat Patient 2 — a 27-year-old schoolteacher with a tuberculin-skin-test reaction of 17 mm, a normal chest radiograph, and no other risk factors — for latent tuberculosis infection. Barton is mistaken in stating that “one cannot conclude that she did not have a tuberculin conversion during the previous two years in the absence of a prior negative tuberculin test.” The definition of tuberculin conversion requires a negative tuberculin skin test within the preceding two years.1 Despite the absence of tuberculin conversion, it would not be unreasonable to treat Patient 2 because of the possibility that she could infect children should tuberculosis develop, although there is no clear indication for the treatment of latent infection in this particular case. This is the rationale for having teachers undergo tuberculin testing before they are employed, which is common practice, as Meyer relates. However, there is no evidence that this policy has decreased cases of tuberculosis or secondary transmission to children. These goals would be better achieved by obtaining chest radiographs in all teachers with either symptoms or a risk factor (e.g., recent arrival in the United States or contact with a person known to have an infectious case) than by tuberculin skin testing. Our recommendation not to provide treatment was meant to emphasize the point that treatment should be directed toward those at risk, instead of random testing of everyone.
We focused on the U.S.-based guidelines for treatment of latent tuberculosis infection, which include the administration of isoniazid for nine months, rifampin for four months, or rifampin and pyrazinamide for two months. As Lepage notes, the recommendations in the United Kingdom also include the administration of isoniazid and rifampin for three months as an alternative regimen, although there has been only one study evaluating this regimen in adults without HIV infection.2
We agree with De Rosa and Craven that patients who are taking anti-TNF monoclonal antibodies such as infliximab are at increased risk for the development of tuberculosis.3 Such patients are examples of those “receiving immunosuppressive therapy,” as we noted in Table 1 of our article, and these patients should be evaluated for treatment of latent tuberculosis infection similarly to those taking corticosteroids. Although it is unclear whether such patients should be considered to have a positive tuberculin reaction if they have only 5 mm of induration on testing (the cutoff point for those taking corticosteroids), we believe that given the significant risk of tuberculosis among patients taking infliximab, the 5-mm reaction is an appropriate threshold.
3 ReferencesRobert M. Jasmer, M.D.
Payam Nahid, M.D.
Philip C. Hopewell, M.D.
San Francisco General Hospital, San Francisco, CA 94110
rjasmer@itsa.ucsf. edu 1
Core curriculum on tuberculosis: what the clinician should know. 4th ed. Atlanta: Centers for Disease Control and Prevention, 2000:29.
2
Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council
CrossRef | Web of Science | Medline3
Keane J ,Gershon S ,Wise RP , et al. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N Engl J Med 2001;345:1098-1104
Full Text | Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Hemda Rosenblum, Howard Amital. (2011) Anti-TNF therapy: Safety aspects of taking the risk. Autoimmunity Reviews 10:9, 563-568
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Iñigo Rúa-Figueroa Fernández de Larrinoa, Celia Erausquin Arruabarrena. (2010) Treatment of ANCA-associated systemic vasculitis. Reumatolog ía Cl ínica (English Edition) 6:3, 161-172
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Shivsharan Kharatmal, Sarbjit Singh Jhamb, Prati Pal Singh. (2009) Evaluation of BACTEC 460 TB system for rapid in vitro screening of drugs against latent state Mycobacterium tuberculosis H37Rv under hypoxia conditions. Journal of Microbiological Methods 78:2, 161-164
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Maria Cristina Gagliardi, Anne Lemassu, Raffaela Teloni, Sabrina Mariotti, Valeria Sargentini, Manuela Pardini, Mamadou Daffé, Roberto Nisini. (2007) Cell wall-associated alpha-glucan is instrumental for Mycobacterium tuberculosis to block CD1 molecule expression and disable the function of dendritic cell derived from infected monocyte. Cellular Microbiology 9:8, 2081-2092
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