The diagnosis and therapy of tuberculosis during the past 100 years.

Methods for the radiographic diagnosis of tuberculosis have improved from simple fluoroscopy to computerized tomography. Although direct smear examination is still the most widely used bacteriological method of diagnosis, cultural methods with selective liquid media are sensitive and rapid. The use of antituberculosis drugs has changed tuberculosis from a disease with about a 50% mortality, treated by measures to collapse the affected lung lesions and by rest for the patient, to a condition successfully curable by chemotherapy. Key steps in the development of modern chemotherapy regimens were the demonstrations in clinical trials that (1) streptomycin was effective; (2) combination of drugs prevented the emergence of drug-resistant Mycobacterium tuberculosis; (3) chemotherapy under domiciliary conditions was effective and did not put family members at risk of infection; (4) patient compliance could be assisted by fully supervised intermittent regimens, or more effectively, by (5) shortening treatment by the introduction of rifampin and pyrazinamide, the two most potent sterilizing drugs, into the regimens. Regimens were divided into an initial intensive phase, while bacterial populations were high, and a longer continuation phase to complete sterilization. Pyrazinamide was shown to sterilize only in the intensive phase. The treatment of nonpulmonary tuberculosis followed the same plan, but when bacterial populations are low, fewer drugs are required in combination.