This project addresses biology and pathogenesis of Candida infection, and includes clinical trials of prevention of cytomegalovirus (CMV) and fungal infection. Studies addressing CMV include prevention of recurrent CMV infection with prophylactic ganciclovir; phase 1 trials of a new human monoclonal antibody with neutralizing activity against CMV (with subsequent efficacy trials to be proposed); and a randomized trial of filtered blood products versus seronegative blood products for prevention of primary CMV infection among seronegative patients. Studies of the biology and pathogenesis of Candid infection include determination of the prevalence of serotype B versus serotype A isolates in colonization or invasive infection of marrow transplant compared with other immunocompromised and immunocompetent patients; sensitivity testing of serotype B versus serotype A isolates and of isolates causing colonization versus invasive disease; determination of the adherence characteristics of Candida isolates from patients with and without invasive disease in a new ex vivo tissue adherence assay using tissues from a variety of immunocompromised and immunocompetent mice, primate tissues, and patient tissues; correlation of the results of the adherence assay with Candida serotype; and evaluation of Candida enolase detection in the blood as a new test for diagnosis of systemic infection. The ex vivo adherence assay will be used to explore the cell or tissue to which Candida adheres, as an initial step in determining the ligand-receptor interactions important in pathogenesis. The new triazole antifungal agent fluconazole will be used in a randomized trial for prophylaxis of fungal infection after transplant. Finally, a series of studies will further explore the ability to transplant human immunodeficiency virus (HIV) positive patients initially using zidovudine, and later other agents including dideoxyinosine (ddl) and soluble CD4, alone and in combination. The goal is to eradicate or sufficiently suppress HIV to protect the new immune system from infection, so that marrow transplant can be successfully used to treat HIV positive patients with an underlying malignancy, or ultimately to treat HIV infection itself.
Showing the most recent 10 out of 788 publications
