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From the time of the discovery of the tubercle bacillus in the late nineteenth century until the introduction of chemotherapy in the mid-twentieth, the role of the laboratory in the management of tuberculosis was limited because the treatment of the disease was nonspecific. The advent of specific chemotherapy and the recognition of human diseases caused by a number of mycobacterial species other than M. tuberculosis increased the scope and importance of the clinical laboratory in guiding the diagnosis and management of mycobacterial disease. This included the isolation of mycobacteria, the identification of the isolates, the determination of their susceptibilities to chemotherapeutic agents and their subtyping for epidemiologic purposes. In spite of the enhanced role it has played in the past forty years, the laboratory's contribution has been impeded by the slow growth of mycobacteria, which causes delays of weeks or months between submission of a specimen and the availability of a definitive report. In the meantime both the urgency and the complexity of diagnosis and management of mycobacterial disease have increased with the emergence of epidemics of these diseases associated with the acquired immunodeficiency syndrome (AIDS). This development has also increased the need for recognition of tubercle bacilli in such specimens as blood and stools, which were only infrequently studied in past years. Recent developments in microchemical and immunologic technology, and especially molecular biology, are greatly reducing the time needed to get information that contributes to diagnosis and management of mycobacterial disease.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper reviews recent information on the systematics and clinical significance of potentially pathogenic environmental mycobacteria. A short history of these mycobacteria is given. Information on species for which clinical and systematic aspects have already been well documented, i.e., Mycobacterium kansasii, M. marinum, M. scrofulaceum, M. simiae, M. szulgai, M. ulcerans, M. xenopi, and members of the M. fortuitum complex, is updated. Although the M. avium complex was extensively reviewed in earlier literature, major new systematic and clinical information is presented in some detail. Species that have received very limited prior coverage, i.e., M. asiaticum, M. haemophilum, M. malmoense, and M. shimoidei, are the main subjects of this review and are discussed in detail. The rare infections attributed to species that are normally considered nonpathogenic, i.e., M. gastri, M. gordonae, the M. terrae complex, and most of the rapidly growing mycobacteria outside of the M. fortuitum complex, are critically reviewed. Finally, suggestions are offered for practical measures that can minimize the risk of failing to isolate or misidentifying some of the more obscure potentially pathogenic environmental mycobacteria that are only infrequently recognized.

The philosophy of the recently proposed "Levels of Laboratory Service" program, which will be so vital to the conduct of a successful outpatient tuberculosis treatment and control program, is presented. The hallmark of this program is the decentralization of the diagnostic/monitoring services as they involve laboratory participation. In the long run this could mean more efficient operation, more reliable reporting, and probably less work for the participating laboratories. The greater emphasis on smear examination (Level I) as a monitoring tool will mean fewer cultures, thereby lessening the load for those laboratories that once went through countless clinically requested exercises of repetitively proving by culture the existence of M. tuberculosis in a given patient. Doubtless, the bulk of the work will be conducted in Level II laboratories; but here, too, identification of the most easily defined pathogen, M. tuberculosis, will minimize the over-all workload for these investigators while decreasing their concern about mycobacteria other than tubercle bacilli. Expertise gained in frequent repetitions of a limited number of tests (niacin, nitrate reduction, and pH 7/68 degrees C catalase) will ensure reliable speciation of the clinically most important Mycobacterium. The work of Level III laboratories should eventually be reduced primarily to organisms other than M. tuberculosis, thereby ensuring that a number of highly competent reference institutions will not only attain proficiency in taxonomic aspects of mycobacteria, but will also reflect the regional picture of the changing patterns in mycobacterial pathogens of man. Participation of laboratories in proficiency testing programs will encourage top-level performance in all areas. Additionally, such testing programs will serve a teaching role; a laboratory need not feel "locked in" at a given service level, but may increase its proficiency and move up a step in terms of the service it provides. In contrast, no laboratory need feel compelled to increase its activities; if daily workloads limit the extent of their involvement with mycobacteria, these laboratories can be confident that other institutions are providing needed services. The success of the entire "Levels of Laboratory Service" program depends on the recognition by individual laboratories of their own workload limitation, the directed motivation of personnel, and the maintenance of a free and open pipeline of communication to laboratories at the next higher level of service.

Sera from patients with disease caused by the Mycobacterium avium complex (M. avium and M. intracellulare), M. kansasii, or M. tuberculosis and from subjects who did not have a mycobacterial disease were tested by enzyme-linked immunosorbent assay against peptidoglycolipid antigens representing each of the 15 most common serovars of the M. avium complex and against crude protein antigen extracts of M. avium and M. tuberculosis. The highly specific peptidoglycolipid antigens yielded positive reactions in 83% of M. avium complex patients, 57% of active-tuberculosis patients, and 14% of subjects without mycobacterial disease. Reactions to more than 1 of the 15 peptidoglycolipid antigens were found only in patients with infections caused by mycobacteria, suggesting that a mycobacterial pulmonary lesion is readily colonized by mycobacteria other than the one that initiated the lesion. The two crude mycobacterial protein antigens were highly cross-reactive, with little if any capacity to discriminate between infections caused by any of the mycobacteria studied. Moreover, they did not appear to be more sensitive than the peptidoglycolipids. The data suggest that it is unlikely that a practical and reliable serological test can be developed that will distinguish between transient subclinical infection and significant disease caused by common environmental mycobacteria, such as members of the M. avium complex. Success in developing such a test for nonenvironmental mycobacteria, such as M. tuberculosis, appears more likely.

Although techniques based on immunologic or chromatographic analyses have been described for identifying mycobacteria in clinical laboratories, most microbiologists continue to rely on a series of specialized physiological and biochemical tests for this purpose. The recognition of additional significant species over the past decade has required the addition of more tests to the battery used for mycobacterial identification. This paper will review briefly the taxonomic status of species likely to be encountered in clinical specimens and the most useful tests for characterizing them. Strategies will be presented for using these tests in the most efficient way to provide optimal resolution of taxa without use of an unreasonably large battery of tests. A brief survey of techniques that may become more practical in the future will also be included.