The past several years have seen an marked rise in the number of cases of tuberculosis in the United States, particularly in urban areas such as New York City, where the increasing incidence of tuberculosis is related to the AIDS epidemic, the deterioration of social conditions, the breakdown of the public health infrastructure, and continuing immigration of persons from countries where tuberculosis infection is endemic. Though the rise of tuberculosis cases is troublesome for many reasons, one of the most disturbing aspects of the current epidemic of tuberculosis is the appearance of large numbers of strains of Mycobacterium tuberculosis which are resistant to one or more of the first-line agents used to treat the disease. Mortality associated with tuberculosis due to infection with a multidrug-resistant strain (MDR-TB) is reported as being extremely high, in many cases no different from the mortality of tuberculosis in the pre-antibiotic era. Though infection control measures may be effective in limiting the spread of MDR-TB, there has undoubtedly been a large reservoir of MDR-TB infection created in the past several years as a result of the many well-documented outbreaks which have occurred. In order to treat the cases of MDR-TB that are occurring now and which will undoubtedly occur in the future, new approaches to treatment will be needed. Promising new therapeutic strategies include those that can deliver high concentrations of effective antituberculosis therapy to the lung without systemic toxicity, and those that can deliver therapy designed to stimulate the host response to tuberculosis to augment killing of mycobacteria.
Specific Aim 1 : To assess the effect of aerosol interferon-gamma (IFN- gamma) on the human host response to tuberculosis, specifically on the ability of alveolar macrophages to kill Mycobacterium tuberculosis.
Specific Aim 2 : To assess the effect of aerosol amikacin on clearance of mycobacteria from the lungs of patients with pulmonary tuberculosis.
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| Schluger, N W; Rom, W N (1998) The host immune response to tuberculosis. Am J Respir Crit Care Med 157:679-91 |
| Condos, R; Rom, W N; Schluger, N W (1997) Treatment of multidrug-resistant pulmonary tuberculosis with interferon-gamma via aerosol. Lancet 349:1513-5 |
