Correspondence
Management of Latent Tuberculosis Infection in Immigrants
N Engl J Med 2003; 348:1289-1292March 27, 2003
- Article
To the Editor:
We applaud the rigorous decision analysis by Khan et al. (Dec. 5 issue),1 who demonstrated the cost effectiveness of screening and treating recent immigrants from countries where tuberculosis is prevalent for latent tuberculosis infection. The investigators also attempted to identify the best treatment regimens for latent tuberculosis infection in various populations from developing countries, on the basis of drug-resistance patterns. However, the differences in direct costs and health benefits among these regimens were relatively small and should be interpreted cautiously. The comparisons were limited, in that the estimates of drug resistance for certain countries (derived from data from the Centers for Disease Control and Prevention [CDC]) were imprecise, the issue of nonadherence under programmatic conditions was not addressed, and the rates and associated costs of adverse events were probably underestimated.
It is important to highlight the recent reports of serious adverse events affecting the liver, some resulting in death, associated with the use of rifampin and pyrazinamide for two months.2 The CDC now recommends a nine-month regimen of daily isoniazid as the preferred treatment for latent tuberculosis infection, or, as an acceptable alternative, a four-month regimen of daily rifampin. Two months of daily rifampin–pyrazinamide may be considered in selected cases when the completion of longer regimens is unlikely and the patient can be monitored closely. The CDC continues to collect reports of severe liver injury (i.e., injury leading to hospital admission or death) due to any regimen for latent tuberculosis infection (telephone 404-639-8117).
2 ReferencesSuzanne M. Marks, M.P.H.
Kashef Ijaz, M.D., M.P.H.
Michael F. Iademarco, M.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 30333
kijaz@cdc.gov 1
Khan K ,Muennig P ,Behta M ,Zivin JG . Global drug-resistance patterns and the management of latent tuberculosis infection in immigrants to the United States. N Engl J Med 2002;347:1850-1859
Full Text | Web of Science | Medline2
Update: fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations -- United States, 2001. MMWR Morb Mortal Wkly Rep 2001;50:733-735
Medline
To the Editor:
Khan et al. appropriately emphasize the importance of treating latent tuberculosis infection in persons at high risk, but they probably overstate the potential of shorter treatment regimens. Evidence for the safety and effectiveness of these regimens is more limited than that for preventive treatment with isoniazid. Neither the effectiveness nor the tolerability of a four-month regimen of rifampin has been studied, and the effectiveness of a two-month regimen of rifampin and pyrazinamide has not been studied in persons who are seronegative for the human immunodeficiency virus (HIV). In the only study of a three-month regimen of rifampin, its effectiveness was 46 percent1; this estimate was not included in the base-line or sensitivity analyses presented by Khan et al. The sample sizes in studies that assessed the tolerability of longer regimens of rifampin have been small,2,3 and therefore caution is warranted before such a regimen is recommended for large-scale application.
The authors also do not account for the cost and complexity of screening more than 600,000 immigrants and providing treatment to more than 200,000 per year. Aside from increasing the treatment of latent infection in recent immigrants (whatever regimen is used), we probably cannot eliminate tuberculosis in this country until the disease is better controlled globally. Improving global control measures is cost effective and also serves the interest of tuberculosis control in this country.
3 ReferencesTimothy Sterling, M.D.
Johns Hopkins University, Baltimore, MD 21231Sonal S. Munsiff, M.D.
Thomas R. Frieden, M.D., M.P.H.
New York City Department of Health and Mental Hygiene, New York, NY 10013
smunsiff@health.nyc. gov 1
Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council
CrossRef | Web of Science | Medline2
Polesky A ,Farber HW ,Gottlieb DJ , et al. Rifampin preventive therapy for tuberculosis in Boston's homeless. Am J Respir Crit Care Med 1996;154:1473-1477
Web of Science | Medline3
Villarino ME ,Ridzon R ,Weismuller PC , et al. Rifampin preventive therapy for tuberculosis infection: experience with 157 adolescents. Am J Respir Crit Care Med 1997;155:1735-1738
Web of Science | Medline
To the Editor:
In their cost-effectiveness analysis, Khan and colleagues compared the expected costs and outcomes of screening by tuberculin testing and the treatment of those with a reaction to the costs and outcomes of no screening, instead of analyzing the incremental costs and effects of replacing the current program of screening by chest radiography. A previous analysis suggested that incremental costs would be substantial and the gains limited.1 Moreover, physicians' adherence in medical evaluations and prescriptions and patients' adherence to screening were assumed to be 100 percent. Patients' adherence to treatment was imputed from expensive clinical trials. However, program evaluations have documented suboptimal adherence, which reduces cost effectiveness, at various steps.1,2 Since the costs of interventions to promote voluntary adherence were not considered, the analysis by Khan and colleagues would be realistic only in the context of legal coercion, which many believe unjust.3 The public health infrastructure required to coordinate and execute such a massive program was ignored, falsely enhancing cost effectiveness.
3 ReferencesDick Menzies, M.D.
Kevin Schwartzman, M.D., M.P.H.
Montreal Chest Institute, Montreal, QC H3A 1A3, Canada
dick.menzies@mcgill. ca 1
Schwartzman K ,Menzies D . Tuberculosis screening of immigrants to low-prevalence countries. Am J Respir Crit Care Med 2000;161:780-789
Web of Science | Medline2
Dasgupta K ,Schwartzman K ,Marchand R ,Tannenbaum TN ,Brassard P ,Menzies D . Comparison of cost-effectiveness of tuberculosis screening of close contacts and foreign-born populations. Am J Respir Crit Care Med 2000;162:2079-2086
Web of Science | Medline3
Coker R ,van Weezenbeek KL . Mandatory screening and treatment of immigrants for latent tuberculosis in the USA: just restraint? Lancet Infect Dis 2001;1:270-276
CrossRef | Medline
To the Editor:
By excluding consideration of HIV infection in their analysis of the incidence of tuberculosis in immigrants because “persons with HIV infection would be excluded from legal immigration in accordance with current U.S. policy,” Khan et al. miscalculate actual conditions. HIV-infected African expatriates are regularly encountered in New York City. Most have non-B subtypes of HIV type 1 infection, suggesting that their infection was acquired from other Africans,1 presumably before entry into the United States. Among 60 HIV-infected African expatriate patients seen at a New York City hospital, tuberculosis was the most common opportunistic infection in the 25 whose HIV test was prompted by symptoms of AIDS.2
2 ReferencesElizabeth R. Jenny-Avital, M.D.
Albert Einstein College of Medicine, Bronx, NY 10461
jennyavita@aol.com 1
Jenny-Avital ER ,Beatrice ST . Erroneously low or undetectable plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid load, determined by polymerase chain reaction, in West African and American patients with non-B subtype HIV-1 infection. Clin Infect Dis 2001;32:1227-1230
CrossRef | Web of Science | Medline2
Jenny-Avital ER . AIDS in Africans living in New York City. Clin Infect Dis 2000;131:267-267 abstract.
Author/Editor Response
We share the concern expressed by Marks et al. about the recent reports of hepatotoxicity with rifampin plus pyrazinamide, and we acknowledge that the data on rifampin-based treatment for latent tuberculosis infection are limited, as noted by Sterling et al. However, the broad use of isoniazid in populations with a high prevalence of resistance is not benign. Treatment of persons with resistant infections needlessly exposes them to the risk of serious adverse reactions, incurs unnecessary costs, and requires a nine-month commitment from which it is unlikely that there will be benefits.1
In our analysis, we established benchmark estimates of the effectiveness of each rifampin-based regimen in relation to a landmark clinical trial.2 Our estimate of the effectiveness of rifampin monotherapy was derived from a study showing the statistical equivalence of three months of rifampin and six months of isoniazid.3 On the basis of these data, many experts consider the effectiveness of rifampin-based regimens to be approximately equivalent to those based on isoniazid.4
Our analysis evaluated the cost effectiveness of treatment of latent tuberculosis infection in the context of the current health care infrastructure in the United States. Since we recognize that limited medical and public health resources may preclude the targeted screening of all persons at high risk, our analysis was designed to facilitate the most efficient use of available resources. Decisions regarding mass screening and large-scale investment in the public health infrastructure must be considered in the context of current national health care priorities.5
The “no intervention” group in our study was not a “no screening” group, as interpreted by Menzies and Schwartzman. Since this group was based on epidemiologic data on tuberculosis in foreign-born persons, it reflects current screening practice for all foreign-born persons in the United States. Among the latter are documented immigrants, who undergo screening by chest radiography, as well as other foreign-born persons who might not have been screened.
We acknowledge that all immigrants with HIV infection might not be identified by the current immigration screening system. Nevertheless, the presence of persons infected with HIV only strengthens the conclusions of our study, since HIV greatly increases the risk of reactivation of latent tuberculosis and thus deepens the benefits of screening.
Finally, we strongly agree that global control of tuberculosis is necessary before its elimination from the United States can realistically be considered. It is our opinion that targeted screening of foreign-born populations at high risk, combined with a strong commitment to global control, is consistent with the national interests of the United States.
5 ReferencesKamran Khan, M.D., M.P.H.
St. Michael's Hospital, Toronto, ON M5B 1W8, Canada
km.khan@utoronto. ca Peter Muennig, M.D., M.P.H.
City University of New York School of Medicine, New York, NY 10031Joshua Graff Zivin, Ph.D.
Columbia University, New York, NY 100321
Fairshter RD ,Randazzo GP ,Garlin J ,Wilson AF . Failure of isoniazid prophylaxis after exposure to isoniazid-resistant tuberculosis. Am Rev Respir Dis 1975;112:37-42
Web of Science | Medline2
Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ 1982;60:555-564
Web of Science | Medline3
Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council
CrossRef | Web of Science | Medline4
Geiter L, ed. Ending neglect: the elimination of tuberculosis in the United States. Washington, D.C.: National Academy Press, 2000.
5
Taylor Z ,O'Brien RJ . Tuberculosis elimination: are we willing to pay the price? Am J Respir Crit Care Med 2001;163:1-2
Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Rajiv Sahni, Cyndee Miranda, Belinda Yen‐Lieberman, J. Walton Tomford, Paul Terpeluk, Pearl Quartey, Lucileia T. Johnson, Steven M. Gordon. (2009) Does the Implementation of an Interferon‐γ Release Assay in Lieu of a Tuberculin Skin Test Increase Acceptance of Preventive Therapy for Latent Tuberculosis Among Healthcare Workers?. Infection Control and Hospital Epidemiology 30:2, 197-199
CrossRef
