Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome

Abstract

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.

Mycobacterium avium infection in HIV-1-infected subjects increases monokine secretion and is associated with enhanced viral load and diminished immune response to viral antigens

“…Disseminated infections with mycobacterial agents may modulate HIV infection, given the fact that mycobacteria and products thereof stimulate the production of cytokines [9,10]. These mediators (especially IL-6 and TNF-a) have been shown to be involved in the superinduction of HIV in T cells and/or monocytic cell lines [13].…”

“…IL-1. lL-6) which induce viral replication, or contribute to the pathophysiology of HIV-I infection by excess TNF-a release [9].…”

Protection against VirulentMycobacterium aviumInfection following DNA Vaccination with the 35-Kilodalton Antigen Is Accompanied by Induction of Gamma Interferon-Secreting CD4+T Cells

“…There is, however, an increasing incidence of opportunistic infections caused by atypical mycobacterial species such as Mycobacterium avium, particularly in human immunodeficiency virus-infected patients (26). Until recently, M. avium complex (MAC) organisms were rarely reported to cause disease in individuals without predisposing lung disease or AIDS (5). Recent reports indicate that pulmonary MAC infections are becoming a more prevalent clinical problem in individuals without predisposing conditions (26), particularly in the older female population (6).…”

Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex

“…M. avium subsp. hominissuis and M. intracellulare are ubiquitous, saprophytic mycobacteria commonly found in soil and water (12,17,28). Best known for causing disseminated infection in patients infected with human immunodeficiency virus, M. intracellulare and M. avium subsp.…”