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Frequency of Isolation of M. avium complex (MAC) from Marrow in Patients Suspected of Disseminated MAC (DMAC) but with Negative Blood Cultures. R. R. MACGREGOR*, D. C. PERLMAN, R. MURPHY, C. INDERLIED, L. BERMUDEZ, J. ANDERSEN, E. BASSILY, S. KOLETAR, D. PETERSON, R. HAFNER, and the ACTG 341 Study Team.
AIDS Clin. Trials Group, Bethesda, MD DMAC is a late complication of AIDS associated with profound immunosuppression. In a prospective multicenter trial, we examined clinical, microbiological, and immunological characteristics of 19 patients with <50 CD4 cells/µl who were not receiving MAC prophylaxis and had > 1 signs/symptoms (s/s) suggestive of DMAC. Evaluations included MAC culture of blood, marrow, respiratory, and GI tracts, plus assays of immune function. Most (84%) were men, 68% were minorities, median age was 40, and 47% had CD4 <20.
MAC was isolated from marrow in 4/19 (21%), and from blood in 1 of these 4. Only 3/19 were colonized with MAC in respiratory or GI tracts; 2 of these also had MAC in marrow. MAC was not isolated from respiratory or GI specimens in the other 2 patients with DMAC. 29% of patients had only 1 symptom, while 18% reported > 3. Weight loss/cachexia (47%) and chills/night sweats (41%) were most common, but the number of s/s was not associated with the probability of having a positive MAC culture. Those who received prophylaxis > 3 months prior to study entry were less frequently MAC+ (1/12) than those with no prior prophylaxis (3/7, p=0.12). In situ staining of marrow macrophages demonstrated TGF-beta production in all 4 patients with MAC grown from marrow vs only 3/15 with negative cultures (p=0.009). No cells stained positive for IL-12 in patients with DMAC. Flow cytometry for cytokine production is pending for blood and marrow cells.
This study offers clinical evidence that MAC may infect tissues before occurrence of continuous bacteremia in some patients with symptoms suggestive of DMAC. Presence of TGF-beta and absence of IL-12 production in marrows of patients with positive marrow cultures is consistent with impaired response to MAC.
Key Words: Bone Marrow, DMAC Pathogenesis, M. Avium Infection
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