The objective of the proposed research is the development of effective and safe drugs for the prevention and treatment of Pneumocystis carinii pneumonitis (PCP). Immunocompromised patients at high risk for PCP, especially those with AIDS, will benefit from such drugs. Currently available therapy is associated with a failure rate of about 25% and adverse effects occur in about 30% of cases. The research is intended to accomplish two aims: the establishment of a method for the in vitro cultivation of P. carinii and its adaptation to drug testing; and, to utilize the corticosteroid-treated rat model to screen new compounds and drug combinations for efficacy against PCP. The major thrust of the work is to cultivate P. carinii in sufficient quantity and purity to provide organisms for basic studies of structure and function. While consideration has been given to past and contemporary studies, the strategy proposed is to investigate through labor-intensive studies unique and often unconventional approaches to microbial cultivation. A wide range of cultural conditions with nutritional options, inhibitor deletions, growth stimulants, physical changes, electrolyte modification and host feeder cells will be investigated. A successful culture system will be utilized to study drug effects on P. carinii mitochondria, as well as overall cytopathogenicity and growth inhibition. The well-established corticosteroid-treated rat model will be used to evaluate new compounds (macrolides, quinolinemethanols, phenylphenols, dihydrofolate reductase and chitin synthesis inhibitors) and drug interactions for synergism. Drugs in or near clinical trials will be studied in rats for their relative efficacies to provide a guide for priorities in clinical trials.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
AIDS and Related Research Study Section 5 (ARRE)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
St. Jude Children's Research Hospital
United States
Zip Code
Choueiry, M A; Scurto, P L; Flynn, P M et al. (1998) Disseminated infection due to Mycobacterium fortuitum in a patient with desmoid tumor. Clin Infect Dis 26:237-8
Oz, H S; Hughes, W T (1997) Pneumocystis carinii infection alters GTP-binding proteins in the lung. J Parasitol 83:679-85
Oz, H S; Hughes, W T (1996) Effect of sex and dexamethasone dose on the experimental host for Pneumocystis carinii. Lab Anim Sci 46:109-10
Oz, H S; Hughes, W T (1996) Acute fulminating babesiosis in hamsters infected with Babesia microti. Int J Parasitol 26:667-70
Oz, H S; Hughes, W T; Vargas, S L (1996) Search for extrapulmonary Pneumocystis carinii in an animal model. J Parasitol 82:357-9
Vargas, S L; Hughes, W T; Wakefield, A E et al. (1995) Limited persistence in and subsequent elimination of Pneumocystis carinii from the lungs after P. carinii pneumonia. J Infect Dis 172:506-10
Hughes, W T; Oz, H S (1995) Successful prevention and treatment of babesiosis with atovaquone. J Infect Dis 172:1042-6
Hughes, W T (1993) Prevention of infections in patients with T cell defects. Clin Infect Dis 17 Suppl 2:S368-71
Hughes, W T (1991) Macrolide-antifol synergism in anti-Pneumocystis carinii therapeutics. J Protozool 38:160S
Hughes, W T; Killmar, J T (1991) Synergistic anti-Pneumocystis carinii effects of erythromycin and sulfisoxazole. J Acquir Immune Defic Syndr 4:532-7

Showing the most recent 10 out of 18 publications