chitosan and plga microspheres as drug delivery ... - UniCA Eprints

1. General IntroductionEven today, more than one hundred year after its first description, TB is still a great healthproblem worldwide. It is estimated that there are 1 billion persons infected with tuberculosisworldwide, with 8 million new cases and 3 million deaths per year (5). Such high mortalityrate seems to be due to progressive HIV infection rather than TB, and the degree ofimmunosuppression being the most important predictor of survival of HIV-TB patients. MTBprobably increases HIV replication by inducing macrophages to produce transactivatingcytokines (TNFα, IL-1, IL-6).However, immunocompromised patients are also at risk of mycobacteria other thantuberculosis (MOTT) infections. Recent reports have described several groups of patientswith acute leukemia, lymphoma, visceral malignancies and treated with immunosuppressivetherapy who have been infected with MOTT such as M. avium, M. fortuitum, M. chelonae,M. scrofulaceum and M. hemophilum (6, 7). Mycobacterium Avium Complex (MAC) cancause pulmonary disease, subacute lymphadenitis and disseminated diseases (8). MAC wasalso recognised in the AIDS pandemic as a cause of serious disseminated infection and wasthe most common cause of systemic bacterial infection in AIDS, affecting more than 50% ofpatients in the developed countries (9). In AIDS patients with disseminated infection, themononuclear phagocyte system is the predominant site of infection, but other organ systemssuch as skin, bone and joints, eyes, thyroid, adrenals, testis and the central nervous system canbe infected (10, 11). Bacteremia occurs in most of these patients, the organism beingpredominantly in circulating monocytes. Monocytes and fixed tissue macrophages are full ofMAC in AIDS patients, indication of the immune deficiency in these individuals (11, 12, 13,14, 15). Furthermore, epidemiological studies suggest that MAC strains associated withpulmonary disease may differ from those associated with disseminated disease in AIDSpatients. Although if the prevalence of disseminated MAC associated disease was high, greatindividual susceptibility, and geographic and seasonal variations has been described. Forinstance, disseminated MAC is rare in Africa, although MAC is prevalent in soil and watersamples from the area where advanced AIDS patients are present (16). This phenomenaremains unexplained, although it is postulated that widespread previous antimycobacterialimmunity from the high rate exposure of Africans to MTB and BCG vaccination may beresponsible. This is supported by data that suggest that prior TB diagnosis may be somehowprotective against disseminated MAC (17). Pathogenesis of MAC infection is incompletelyunderstood. Disseminated MAC is usually believed to follow primary acquisition of themycobacteria. It appears that MAC first colonizes the gastrointestinal (GI) tract or respiratory11