ORGANISMS of the Mycobacterium avium complex have long been recognized as an uncommon cause of pneumonia in persons with chronic lung disease.1 2 3 4 Organisms of this complex, which comprises two closely related species, M. avium and M. intracellulare, appear to have little virulence in the normal host. Before the acquired immunodeficiency syndrome (AIDS) epidemic, disseminated infection with M. avium complex was extremely rare; by 1980, only 24 cases had been reported in the medical literature.5 Beginning in 1982, however, when the infection was recognized in patients with AIDS, the number of cases increased dramatically. At first, the minimal inflammatory response . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199105093241906

Mycobacterium avium complex infection in the acquired immunodeficiency syndrome.

Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing is of increasing interest and importance as new effective antimicrobial agents are identified and evaluated. Antimicrobial resistance has already emerged as an important problem, and methods for circumventing resistance that use combination therapies are now being studied.

The Mycobacterium avium complex.

The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population.

Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome.

http://ntur.lib.ntu.edu.tw/bitstream/246246/158943/1/30.pdf

Endoscopic appearance of GI mycobacteriosis caused by the Mycobacterium avium complex in a patient with AIDS: case report and review.

Intraperitoneal injection of glycopeptidolipid (GPL) antigens from Mycobacterium avium complex serovar 4 resulted in the decreased ability of murine splenic lymphocytes to respond to nonspecific-mitogen-induced blastogenesis when exposed to concanavalin A, phytohemagglutinin, and lipopolysaccharide. Adherent cell depletion and cell mixing experiments with T lymphocytes indicated that macrophages were not a major contributor to the immunosuppression observed in this study. Enumeration of splenic lymphocytes by means of flow-cytometry with fluorescein isothiocyanate-conjugated monoclonal antibodies demonstrated that intraperitoneal injection of GPL antigens resulted in a significant decrease in Thy-1+ and Lyt-1+ cells but no change in the numbers of Lyt-2+ cells. Treatment with GPL antigens in vitro affected the ability of splenic mononuclear cells to respond optimally for concanavalin A-induced blastogenesis at 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml and lipopolysaccharide-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. However, in vitro treatment with GPL antigens did not affect phytohemagglutinin-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. These findings suggest that GPL antigens or their metabolites affect lymphocyte function and may be important cofactors in the overall pathogenesis of M. avium complex infections.

https://iai.asm.org/content/iai/56/5/1044.full.pdf

Modified lymphocyte response to mitogens after intraperitoneal injection of glycopeptidolipid antigens from Mycobacterium avium complex.

A 40-year-old bisexual man with the acquired immunodeficiency syndrome developed abdominal pain and bloody diarrhea. At sigmoidoscopy, the mucosa of the rectum and sigmoid colon was edematous, erythematous, and friable, with multiple linear and oval erosions. Histologic examination of rectal biopsies demonstrated innumerable acid-fast bacilli free and within macrophages of the lamina propria. Mycobacterium avium-intracellulare was cultured from the rectal biopsy specimens. Pulmonary tissue and bone marrow cultures also demonstrated this organism. Therapy with several antimycobacterial agents resulted in improvement of symptoms. Among immunocompromised patients the spectrum of enteric pathogens causing colitis should be expanded to include Mycobacterium avium-intracellulare, a potentially treatable organism.

Schwartz Is

Papers

Mycobacterium avium-intracellulare-associated colitis in a patient with the acquired immunodeficiency syndrome.