Page 206(CDC) should be key, establishing and using animal models to test effectiveness and safety of potential vaccines.
To confirm the diagnosis of tuberculosis, the laboratory must isolate Mycobacterium tuberculosis from the patient's specimen. This has been true since the laboratory was first able to isolate tubercle bacilli, even if guinea pig inoculation were needed to improve the chances of isolation by passage in a highly susceptible host. When specific therapeutic regimens for the treatment of tuberculosis became available in the 1950s, the incidence of the disease began to decline to such an extent that 40 years later we were able to anticipate its eradication in the United States. As quickly as the number of cases declined, tuberculosis laboratory services in diagnostic mycobacteriology became less important in the overall activities of public health and clinical laboratories. Laboratories at that time were limited to the use of the slow, but reliable, methods that had been developed over decades. Therefore, detection of acid-fast bacilli by a specific stain could be accomplished in a local laboratory or on the ward of a hospital within hours of specimen collection, but isolation of tubercle bacilli and identification based on unique characteristics required inoculation of many tubes of solid media and subcultures to measure biochemical reactions. Drug susceptibility tests also required the inoculation of a solid medium prepared with assay levels of the drugs. Results of these tests could take from 6 weeks to 6 months to complete, and during this time patients with tuberculosis were continuing to be in contact with community members, continuing to infect others by exposing them to aerosols produced by coughing and sneezing.
The laboratories responsible for tuberculosis diagnosis were not ready for the expanded workload that resulted from the increased number of cases that began to occur in 1986, when, without precedent in this century, the tuberculosis case rate reversed a downward trend and began to increase. Nor were they prepared for testing the strains resistant to multiple drugs that were isolated from nosocomial outbreaks of tuberculosis in the last decade of the century.
New procedures for the isolation and identification of M. tuberculosis were developed, notably the radiometric BACTEC system (Roberts et al., 1983), high performance liquid chromatography (HPLC) analysis of mycolic acids for speciation (Butler et al., 1992), molecular procedures for identification (Shinnick and Jonas, 1994), and fingerprinting techniques which provide data useful in epidemiologic studies (van Embden et al., 1993). However, laboratories were slow to incorporate the new techniques for identification and drug susceptibility testing when they became avail