Tuberculosis: An Unconquered Problem
ABSTRACT & COMMENTARY
Synopsis: In a database examining tuberculosis drug resistance between 1994 and 1997, resistance to anti-tuberculosis drugs was found in all 35 countries and regions surveyed.
Source: Pablos-Mendez A, et al. N Engl J Med 1998;338:1641-1649.
Tuberculosis remains a worldwide epidemic disease, with the greatest mortality seen in third-world countries. The number of cases in the United States remains high but has declined in the 1990s.1,2 Resistance of tuberculosis to antibiotic therapy was first noted with streptomycin monotherapy in the 1940s. However, this problem remained relatively uncommon through the 1990s. Recently, there have been many reports of multidrug resistance to tuberculosis, especially in patients with HIV infection where delayed recognition and failure to consider the disease resulted in a very high mortality rate. Transmission among residents of correctional facilities, health care facilities, and other congregate-living situations developed where highly susceptible populations were housed.
In order to evaluate the global threat of drug-resistant tuberculosis, Pablos-Mendez et al reported the work of the IUAT and World Health Organization's database of drug-resistant tuberculosis. This surveillance project demonstrated that, among patients with no prior history of treatment, an average of 10% of TB strains was resistant to one drug. Drug resistance was reported from all countries and regions surveyed. In patients with prior treatment, the average prevalence of all resistance increased to 36%, with the prevalence of multidrug resistance at 13%. Resistance to all four drugs, INH, streptomycin, rifampin, and ethambutol, was very uncommon (median, 0.2%). Re-treatment resulted in the more frequent acquisition of resistance (median, 36%). Combined prevalence of resistance to any of the four drugs ranged from 2.3% in the Czech Republic to 42% in the Dominican Republic, with an average value of 12.6%.
COMMENT BY ALAN M. FEIN, MD
Given the significance of tuberculosis as a worldwide cause of morbidity and mortality, the importance of TB drug resistance is significant. How do organisms become resistant to antituberculosis therapy? Usually, the problem of resistance results from the emergence of resistant strains during inadequate treatment due to irregular drug supplies, inappropriate regimens, or, in the United States, poor compliance. When patients are infected with resistant strains, the likelihood of a positive outcome is significantly diminished. This has been documented in third world countries in AIDS patients and in patients with malnutrition. Therefore, the study of the Global Tuberculosis Project of the World Health Organization-IUATLD is important. It serves as a reminder that no country or region is immune to the problem of drug resistance. The authors point out that the high prevalence of multidrug resistance in the Dominican Republic is likely the result of either weaknesses in the tuberculosis control program or immigration between the Dominican Republic and New York, where a very high prevalence of multidrug resistance was reported in the 1990s. Interestingly, the African countries reported low antituberculosis drug resistance, probably because of the late arrival and the unavailability of rifampin. Although tuberculosis is endemic throughout Asia, there was little primary drug resistance. This was not the case in India, the site of more than one-third of the worldwide cases of tuberculosis, where the prevalence of multidrug resistance was as high as 13%. In the United States, where drug susceptibility is relatively high at 88%, resistance to any drug still remained at the 12% level, and resistance to all four drugs was almost 1%. INH resistance was most common at 8%. The importance to directly observed therapy to ensure compliance with antituberculosis therapy must be stressed as well as never adding a single drug to a failing regimen. While many physicians are familiar with the basics of TB treatment, it is important to involve infectious disease, pulmonary specialists, and local health departments in this effort to avoid the problems of drug resistance resulting from noncompliance.
References
1. Aland D, et al. N Engl J Med 1994;330:1710-1716.
2. Small PM, et al. N Engl J Med 1993;328:1137-1144.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content