Opportunistic infections in intestinal dysfunction &wasting

Harvard University (Medical School), Boston MA

Investigators

Linked publications & trials

Abstract

Project will test the hypothesis that chronic infections of the gastrointestinal (GI) tract lead to gut dysfunction which reduce nutritional intake, and over a period, contribute to wasting in AIDS. The proposal will also address several related questions. In particular, we will determine the manner in which enteric opportunistic infections (OIs) predispose SIV-infected monkeys to wasting and rapid disease course. We will specifically target the role of Cryptosporidium parvum, Enterocytozoon bieneusi, and Mycobacterium avium complex (MAC), and determine their contribution, if any, to gut dysfunction. We will determine whether chronic OIs cause gut dysfunction and wasting in AIDS regardless of occurrence of significant gastrointestinal symptoms, namely profound diarrhea.. In addition, we believe that the location(s) in the gut of infections such as with C. attention will be directed to examine the role of the mucosal immune status of the SIV-infected macaque which permits the establishment of persistent infection with certain OIs. Finally, the structure-function relationship of the gut mucosa of macaques infected with 3 0Is, will be compared in Using chambers with mucosa of animals infected with SIV only. Specific Aim 1 will investigate the contribution of OIS, namely C. parvum, E. bieneusi and MAC to wasting in AIDS, using the SIV-infected rhesus macaque model; specifically: a) whether persistent infections with the 3 OIS must result in profound diarrhea to contribute to wasting and more rapid disease progression, b) the effects of location and severity of OIS on gut structure and function, c) the nature and extent of immune dysfunction necessary to permit persistent infection with these OIS on gut structure and function, c) the nature and extent of immune dysfunction necessary to permit persistent infection with these OIS. In Specific Aim 2, we will monitor a cohort of approximately 70 SIV-infected macaques with circulating CD4 counts of less than or equal too 500/mul of blood to determine the correlation, if any, between spontaneous acquisition of C. parvum, E. bieneusi, or MAC and the following parameters: a) CD4+ T cell numbers in peripheral blood, b) viral load, c) changes in stool character and relation to extent of OI excretion, d) body weight loss, e) levels of serum micronutrients, body composition and extent to tempo wasting, and f) extent of gut dysfunction in necropsy.