Correspondence
Drug-Resistant Tuberculosis in New York City
N Engl J Med 1993; 329:134-135July 8, 1993
- Article
To the Editor:
In their article on drug-resistant tuberculosis in New York City, Frieden et al. (Feb. 25 issue)1 demonstrate that cases of such disease are cause for serious concern. I wonder, however, whether the authors studied a representative population of patients. The survey population consisted of patients who had a positive culture for Mycobacterium tuberculosis during April 1991. Such a survey represents neither incidence nor prevalence. Like autopsy studies, laboratory-based surveys are subject to selection bias and may oversample patients with severe morbidity. Patients with treatment failure, relapse, or drug resistance are more likely to undergo serial drug-susceptibility testing than patients who respond to therapy or have drug-susceptible disease. Such possible bias is suggested by the fact that the majority of study patients with isolates available for testing (239 of the 466 patients) were reported to have previously received treatment. What proportion of the total number of cases of tuberculosis in New York City that were reported to the Centers for Disease Control and Prevention during this period was included in the study? What proportion of patients in the city's tuberculosis registry in April 1991 was included? How did patients with tuberculosis who were included in the study compare with those who were not, in terms of demographic and clinical characteristics?
Frieden et al. use a definition of patients with previous treatment that differs from the federal definition of patients with recurrent disease who had confirmed tuberculosis in the past, were discharged from or lost to supervision for more than 12 months, and who had confirmed disease again2. In 1990, only 3.3 percent of patients with tuberculosis from New York City (117 of 3520 patients) were reported to have recurrent disease3. How many of the 239 patients with previous treatment were reported to the federal government as having recurrent tuberculosis, and over what period were they reported?
3 ReferencesKathleen F. Gensheimer, M.D., M.P.H.
Maine Department of Human Services, Augusta, ME 043331
Frieden TR ,Sterling T ,Pablos-Mendez A ,Kilburn JO ,Cauthen GM ,Dooley SW . The emergence of drug-resistant tuberculosis in New York City. N Engl J Med 1993;328:521-526
Full Text | Web of Science | Medline2
Kopanoff DE ,Snider DE Jr ,Johnson M . Recurrent tuberculosis: why do patients develop disease again? A United States Public Health Service cooperative survey. Am J Public Health 1988;78:30-33
CrossRef | Web of Science | Medline3
Centers for Disease Control. Tuberculosis statistics in the United States, 1990. Atlanta: Department of Health and Human Services, 1992.
To the Editor:
Frieden et al. do not cite data to support their conclusion that close surveillance of M. tuberculosis isolates would prevent or control the emergence of drug-resistant isolates. A high percentage of the patients with drug-resistant isolates had previously had such isolates, including patients who had been infected before their previous treatment for tuberculosis. There is nothing to suggest that the spread of the disease or the overall prognosis would be altered by close follow-up of treatment in such patients. Goble et al.1 point out that the treatment of patients with drug-resistant M. tuberculosis has had poor results, even when the patients receive the best available treatment.
. . . Until effective drugs are developed to treat drug-resistant tuberculosis, we can expect further increases in the number of cases of this devastating illness.
1 ReferencesIan Joffe, M.D.
Albert Einstein Medical Center, Philadelphia, PA 191411
Goble M ,Iseman MD ,Madsen LA ,Waite D ,Ackerson L ,Horsburgh CR Jr . Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl J Med 1993;328:527-532
Full Text | Web of Science | Medline
To the Editor:
. . . Although Frieden et al. tabulated the high frequency of infections with human immunodeficiency virus (HIV) in the total population studied, they did not specify the HIV status of the 7 percent of untreated patients in whom tuberculosis resistant to both isoniazid and rifampin developed. Their report provides no evidence about the likelihood of the spread of tuberculosis resistant to isoniazid and rifampin to immunocompetent persons. A recent study showed increased nosocomial transmission of tuberculosis from HIV-infected patients, but all subjects with secondary cases who were tested had drug-susceptible organisms.1 The study by Frieden et al. is in fact reassuring in its demonstration that the spread of tuberculosis resistant to isoniazid and rifampin to persons without HIV infection was rarely observed in New York City in 1991.
1 ReferencesHarold L. Israel, M.D., M.P.H.
Jefferson Medical College, Philadelphia, PA 191071
Dooley SW ,Villarino ME ,Lawrence M , et al. Nosocomial transmission of tuberculosis in a hospital unit for HIV-infected patients. JAMA 1992;267:2632-2634
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Author/Editor Response
The authors reply:
To the Editor: In response to Dr. Gensheimer, our investigation was designed to measure drug susceptibility in every New York City patient with a positive culture for M. tuberculosis in April 1991. We chose this design to estimate drug resistance among both incident and prevalent documented culture-positive cases. All culture-positive incident cases reported during these 30 days were included in the study; the proportion of prevalent cases represented by the 239 previously treated patients studied is not known. As we noted, only 14 patients met the criteria for relapse. The critical issue, however, is whether a patient had previous treatment with antituberculosis medications and was therefore at increased risk for drug resistance.
Dr. Joffe questions the value of surveillance. Surveillance for drug-resistant tuberculosis has enabled the New York City Department of Health to recognize and control outbreaks of tuberculosis, provide important clinical information to physicians, guide initial antituberculous therapy, monitor the adequacy of treatment, document the need for additional resources, and target the deployment of personnel. Although some patients have M. tuberculosis isolates that do not respond to treatment, effective isolation and treatment of patients with multidrug-resistant tuberculosis can effectively control disease and prevent its transmission. Even patients with severe immunosuppression and infection with highly resistant strains of tuberculosis, when effectively treated, have had a clinical response, conversion of cultures to negative, and prolonged survival (New York City Department of Health: unpublished data).
In response to Dr. Israel, the transmission of multidrug-resistant tuberculosis predates the HIV epidemic. In our survey, 40 of the 89 patients with such disease (45 percent), including 4 of 17 without previous treatment (24 percent), had no documentation of HIV infection. The association between HIV positivity and drug resistance may, as we indicated, reflect an increased likelihood of exposure to and infection with these strains, decreased virulence of drug-resistant isolates, or simply more frequent and rapid progression to active tuberculosis among immunocompromised persons infected with M. tuberculosis1. This last explanation may be very important. If 100 people, half of whom were infected with HIV, were exposed to and infected with multidrug-resistant tuberculosis today, there would probably be more than 20 cases among HIV-seropositive patients in the next two years, but only 2 to 3 cases among immunocompetent patients. If HIV infection predisposed people not only to progression to active tuberculosis but also to infection with M. tuberculosis if they were exposed, then this difference would be even more marked.
HIV-infected patients in New York City are more likely to have drug-resistant isolates than uninfected persons. Most, however, still have susceptible isolates. HIV-infected patients should undergo early tuberculin skin testing and, if the results are positive, should receive preventive therapy with isoniazid. This therapy is highly effective in preventing drug-susceptible tuberculosis in both HIV-negative and HIV-positive patients2-4.
4 ReferencesThomas R. Frieden, M.D., M.P.H.
Samuel W. Dooley, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 303331
Selwyn PA ,Hartel D ,Lewis VA , et al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med 1989;320:545-550
Full Text | Web of Science | Medline2
International Union Against Tuberculosis Committee on Prophylaxis
Web of Science | Medline3
Comstock GW ,Baum C ,Snider DE Jr . Isoniazid prophylaxis among Alaskan Eskimos: a final report of the Bethel isoniazid studies. Am Rev Respir Dis 1979;119:827-830
Web of Science | Medline4
Selwyn PA ,Sckell BM ,Alcabes P ,Friedland GH ,Klein RS ,Schoenbaum EE . High risk of active tuberculosis in HIV-infected drug users with cutaneous anergy. JAMA 1992;268:504-509
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Abha Choudhary, Meenakshi N. Vyas, Nand K. Vyas, Zengyi Chang, Florante A. Quiocho. (1994) Crystallization and preliminary x-ray crystallographic analysis of the 38-kda immunodominant antigen of mycobacterium tuberculosis. Protein Science 3:12, 2450-2451
CrossRef
