Correspondence
Antituberculosis-Drug Resistance
N Engl J Med 1998; 339:1079-1080October 8, 1998
- Article
To the Editor:
The article “Global Surveillance for Antituberculosis-Drug Resistance, 1994–1997” by Pablos-Méndez et al. (June 4 issue)1 is a clarion call to action by governments and health officials worldwide to combat the increasing prevalence of multidrug-resistant tuberculosis. The prevalence of this disease may in fact be higher than reported, because of two limitations of the study. First, data from regions in which the disease is highly endemic, such as China and most of India, were not obtained. Second, the study included relatively few countries in Africa and none in the Middle East. Furthermore, the ongoing pandemic of human immunodeficiency virus (HIV) infection is a major factor in the projected increases in the incidence of multidrug-resistant tuberculosis.2-4 . . .
4 ReferencesKirk M. Chan-Tack, M.D.
Hospital of the University of Pennsylvania, Philadelphia, PA 191041
Pablos-Mendez A ,Raviglione MC ,Laszlo A , et al. Global surveillance for antituberculosis-drug resistance, 1994-1997. N Engl J Med 1998;338:1641-1649
Full Text | Web of Science | Medline2
Raviglione MC ,Snider DE Jr ,Kochi A . Global epidemiology of tuberculosis: morbidity and mortality of a worldwide epidemic. JAMA 1995;273:220-226
CrossRef | Web of Science | Medline3
Dooley SW ,Jarvis WR ,Martone WJ ,Snider DE Jr . Multidrug-resistant tuberculosis. Ann Intern Med 1992;117:257-259
Web of Science | Medline4
Barnes PF ,Lee HQ ,Davidson PT . Tuberculosis in patients with HIV infection. Med Clin North Am 1993;77:1369-1390
Web of Science | Medline
To the Editor:
The report by Pablos-Méndez et al. on antituberculosis-drug resistance is important, but the results should be taken with a grain of salt. The authors found high prevalences in the former Soviet Union, the Dominican Republic, and Argentina. However, the samples analyzed were not randomly selected; they were convenience samples of biologic material submitted to the laboratories for analysis. The more samples we take, the more resistance we will find. The use of these data to support a hypothesis such as that “migration between the Dominican Republic and New York City” may be responsible for the high prevalence is therefore problematic, because there might have been oversampling of patients with the more complicated cases. The high prevalence found in Argentina could be the result of an extensive search for multidrug resistance. In countries where no such search is being conducted, no multidrug resistance will be found.
Jose F. Diaz, M.D.
Johns Hopkins School of Public Health, Baltimore, MD 21205To the Editor:
The report by Pablos-Méndez et al. pointing out the alarming worldwide threat imposed by multidrug-resistant tuberculosis prompts us to comment on the clinical, social, and financial impact of this problem.
We studied the outcome of treatment in 30 consecutive patients (19 male and 11 female) with multidrug-resistant tuberculosis who were referred to our tertiary care tuberculosis unit between 1985 and 1996. The mean age was 34 years (range, 15 to 82); none of the patients were HIV-seropositive; and 23 were foreign-born. The majority (27 patients) had pulmonary tuberculosis, typically with apparently active disease. All patients were culture-positive on admission, with strains that were resistant to isoniazid and rifampin (by definition), but streptomycin resistance was present in strains from 20 patients, and resistance to both pyrazinamide and ethambutol was present in strains from 5 patients. In 17 patients, previous tuberculosis treatment was documented, and 10 patients were known to have had no prior treatment. Twenty-seven patients with pulmonary tuberculosis had smear-positive sputum samples. Smears of sputum samples from most of these patients converted to negative within eight weeks, but four converted to negative only after a median period of two years. Inpatient treatment lasted a mean of 173 days (range, 31 to 481).
Patients were treated with seven drugs on average. Side effects were common, as were language and cultural barriers between patients and care providers. Yet compliance was high, with directly observed chemotherapy during in-patient treatment. Tuberculosis treatment was continued until six months after the conversion of sputum cultures; one patient received additional surgical treatment for the control of tuberculosis, and two others underwent surgery for aspergilloma after successful tuberculosis treatment.
The estimated cost of treatment (including the cost of drugs and the admission fees) was $60,000 per patient. The mean length of follow-up was 2053 days (range, 497 to 3892); none of the patients were lost to follow-up. Patients were considered cured if the clinical response was favorable and if cultures and directly obtained smears remained negative after the completion of treatment. Six patients died, three with active tuberculosis and three of unrelated conditions. Our results compare favorably with the results of Goble et al.1 but are similar to those for patients without HIV in the studies by Park et al.2 and Telzak et al.3
The costs of treating multidrug-resistant tuberculosis are tremendous, both economically and in terms of human suffering, although in affluent societies the mortality rate may have been overestimated in the past. Pablos-Méndez et al. rightly call for increased global efforts to combat the effects of poor tuberculosis-control programs, especially in developing countries.4
4 ReferencesWya A. Geerligs
Groningen University School of Medicine, 9700 RB Groningen, the NetherlandsRichard van Altena, M.D.
Beatrixoord, 9750 RA Haren, the NetherlandsTjip S. van der Werf, M.D., Ph.D.
Groningen University Hospital, 9700 RB Groningen, the Netherlands1
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 | Medline2
Park MM ,Davis AL ,Schluger NW ,Cohen H ,Rom WN . Outcome of MDR-TB patients, 1983-1993: prolonged survival with appropriate therapy. Am J Respir Crit Care Med 1996;153:317-324
Web of Science | Medline3
Telzak AE ,Sepkowitz K ,Alpert P , et al. Multidrug-resistant tuberculosis in patients without HIV infection. N Engl J Med 1995;333:907-911
Full Text | Web of Science | Medline4
van der Werf TS ,Groothuis DG ,van Klingeren B . High initial drug resistance in pulmonary tuberculosis in Ghana. Tubercle 1989;70:249-255
CrossRef | Medline
Author/Editor Response
The authors reply:
To the Editor: Chan-Tack is correct in pointing out that the results of the global project cannot be used as an atlas of antituberculosis-drug resistance. The World Health Organization and the International Union against Tuberculosis and Lung Disease are currently expanding drug-resistance surveillance in the Middle East (Iran and Morocco), Africa (Uganda, Guinea, Mozambique, and the Gambia), Russia (St. Petersburg and Archangel oblasts), China (Guangdong and Zhejiang provinces), and India (Delhi and five other states).
Diaz attributes the high prevalence of drug resistance found in three countries to biased sampling. The survey in the Ivanovo oblast region of Russia tested all smear-positive cases during the study period, and was not just a convenience sample. The survey in the Dominican Republic used weighted-clusters methods, in which samples were obtained from consecutive patients in each of the selected diagnostic centers in the country.1 Our data cannot address the contribution, if any, of migration between the Dominican Republic and New York City to the levels of multidrug resistance in either setting. The cluster sampling in Argentina was not random but included 80 reference centers in 18 of the 24 districts that reported 93 percent of the cases of tuberculosis in the country; each center received consecutive samples from urban and rural clinics during a six-month period. Although documented outbreaks among HIV-positive patients in metropolitan hospitals may have contributed to the high prevalence of multidrug resistance in Argentina,2 the problem worldwide was associated with inadequate control of tuberculosis.
The report of Geerligs et al. further illustrates the costs and toxicity associated with the treatment of multidrug-resistant tuberculosis. Preventing the emergence of multidrug resistance in the first place — with a solid control program and standardized regimens — is a priority of the World Health Organization,3 especially in resource-poor countries.
3 ReferencesAriel Pablos-Méndez, M.D., M.P.H.
Columbia University, New York, NY 10032Mario C. Raviglione, M.D.
Paul Nunn, M.D.
World Health Organization, 1211 Geneva 27, Switzerland1
Espinal MA ,Baez J ,Soriano G , et al. Drug-resistant tuberculosis in the Dominican Republic: results of a nationwide survey. Int J Tuberc Lung Dis 1998;2:490-498
Web of Science | Medline2
Morcillo N ,Alito A ,Romano MI , et al. Multidrug resistant tuberculosis outbreak in Buenos Aires: DNA fingerprinting analysis of isolates. Medicina (B Aires) 1996;56:45-47
Web of Science | Medline3
Tuberculosis Programme. Framework for effective tuberculosis control. Geneva: World Health Organization, 1994. (WHO/TB/94.179.)
- Citing Articles (2)
Citing Articles
1
Espinal, Marcos A., Laszlo, Adalbert, Simonsen, Lone, Boulahbal, Fadila, Kim, Sang Jae, Reniero, Ana, Hoffner, Sven, Rieder, Hans L., Binkin, Nancy, Dye, Christopher, Williams, Rosamund, Raviglione, Mario C., . (2001) Global Trends in Resistance to Antituberculosis Drugs. New England Journal of Medicine 344:17, 1294-1303
Full Text2
Gerd Fätkenheuer, Henri Taelman, Philippe Lepage, Achim Schwenk, Richard Wenzel. (1999) The return of tuberculosis. Diagnostic Microbiology and Infectious Disease 34:2, 139-146
CrossRef
