Disseminated Mycobacterium avium complex (MAC) infection has become an increasingly common focus of the medical care of patients with advanced AIDS in the United States. Prevention of MAC infection is therefore a major priority, but the only preventive strategy in use or under investigation is chemoprophylaxis, an approach with significant shortcomings (incomplete efficacy, side effects, drug interactions, potential for resistance, expense). Our current international epidemiologic study has provided new insights which suggest that MAC infection might be prevented by two different strategies: (l) Avoiding exposure to MAC: We have used pulsed field gel electrophoresis (PFGE) analysis of clinical and environmental isolates of MAC to demonstrate that recirculating institutional hot water systems are a source of MAC. Our epidemiologic analysis indicates that exposure to indoor pools is a risk factor for disseminated MAC. (2) Immunizing against MAC: We have determined that AIDS patients in developing countries appear to be protected against MAC by broad mycobacterial immunity (BCG, tuberculosis), and AIDS patients in developed countries with intense occupational exposure to water or soil (environmental sources of MAC) before the onset of HIV infection are protected against disseminated MAC. The present prod is designed to (i) use the techniques we have developed to identify additional specific sources of MAC exposure and infection, and (ii) to use the serum samples we have collected to identify a serum marker of prior mycobacterial exposure which correlates with the protection we have observed in the epidemiologic study. 400 HIV-infected patients from the United States (New Hampshire, Boston, New York, Atlanta) and Finland with CD4 counts <100/mm3 and no prior disseminated MAC infection will be entered into the 3 year study. A baseline environmental exposure questionnaire will be completed, a serum sample will be obtained, and the patient will be instructed in the use of a 5 day environmental exposure diary. Results of the baseline questionnaire and diary will be used to identify high risk exposures; 3 water samples will be obtained from these sources and cultured for MAC (total 1200 water samples, estimated 960 positive). Mycobacterial blood cultures will be obtained based on standard clinical criteria. Clinical isolates will be obtained for each new diagnosis of MAC (estimated 83 patients). All isolates will be analyzed by PFGE; an environmental source with an isolate whose PFGE pattern matches a clinical isolate will be identified as the source of infection. Characteristics of MAC positive water system samples (water temperature, holding tank, age of system) will be determined in a case-control analysis. In the second component of the study, antibodies to broad (lipoarabinomannin) and specific (glycopeptidolipid, mig) mycobacterial antigens will be determined on baseline serum samples collected during both the current and proposed studies to determine whether antibody markers of infection acquired prior to HIV infection are associated with a decreased risk of MAC (protective immunity) or an increased risk of MAC (reactivation of latent disease).
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