The Developmental Therapeutics Branch, Basic Research and Development Program, Division of AIDS, as part of its mission, facilitates research efforts related to the discovery and development of new therapies for the treatment of HIV infection and the opportunistic infections (OIs) associated with AIDS. Between 10 and 40 % of AIDS patients in the United States are at risk of developing toxoplasmic encephalitis (TE) through reactivation of latent Toxoplasma infections. Current therapies for TE have proven toxic, expensive, or only partially effective. Development of new, more efficacious therapeutic agents is of utmost importance, yet it has been limited by l) the difficulty of preclinical testing of potential therapies 2) the general lack of pharmaceutical industry research and development in this area, and 3) the relative lack of information on the biological and immunologic processes that control chronic and latent Toxoplasma infections. This contract will provide a critical resource for expeditious evaluations of new therapies for toxoplasmic encephalitis and the continued development of in vivo and in vitro models for toxoplasmic encephalitis and latent infection. This project will complement other activities in the Division's strategy to stimulate OI drug discovery and development by providing in vivo and in vitro test systems for TE that are not readily available to the scientific community. Such a resource will allow NIAID to provide critical support for investigator-initiated drug discovery for TE, to stimulate private sector sponsorship of new drugs, to perform comparative studies of drugs and drug combinations to be used in multiple OI prophylaxis studies, and contribute essential information for the design of clinical studies.

Project Start
1993-09-30
Project End
1998-09-29
Budget Start
1993-09-30
Budget End
1995-01-31
Support Year
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Palo Alto Medical Foundation Research Institute
Department
Type
DUNS #
622276137
City
Palo Alto
State
CA
Country
United States
Zip Code
94301
Araujo, Fausto G; Slifer, Teri (2003) Different strains of Toxoplasma gondii induce different cytokine responses in CBA/Ca mice. Infect Immun 71:4171-4
Yardley, Vanessa; Khan, Anis A; Martin, Michael B et al. (2002) In vivo activities of farnesyl pyrophosphate synthase inhibitors against Leishmania donovani and Toxoplasma gondii. Antimicrob Agents Chemother 46:929-31
Khan, A A; Lambert Jr, L H; Remington, J S et al. (1999) Recombinant bactericidal/permeability-increasing protein (rBPI21) in combination with sulfadiazine is active against Toxoplasma gondii. Antimicrob Agents Chemother 43:758-62
Khan, A A; Araujo, F G; Brighty, K E et al. (1999) Anti-Toxoplasma gondii activities and structure-activity relationships of novel fluoroquinolones related to trovafloxacin. Antimicrob Agents Chemother 43:1783-7
Khan, A A; Slifer, T R; Araujo, F G et al. (1999) Quinupristin-dalfopristin is active against Toxoplasma gondii. Antimicrob Agents Chemother 43:2043-5
Khan, A A; Slifer, T R; Araujo, F G et al. (1999) Effect of clarithromycin and azithromycin on production of cytokines by human monocytes. Int J Antimicrob Agents 11:121-32
Khan, A A; Slifer, T R; Remington, J S (1998) Effect of trovafloxacin on production of cytokines by human monocytes. Antimicrob Agents Chemother 42:1713-7
Khan, A A; Nasr, M; Araujo, F G (1998) Two 2-hydroxy-3-alkyl-1,4-naphthoquinones with in vitro and in vivo activities against Toxoplasma gondii. Antimicrob Agents Chemother 42:2284-9
Araujo, F G; Khan, A A; Bryskier, A et al. (1998) Use of ketolides in combination with other drugs to treat experimental toxoplasmosis. J Antimicrob Chemother 42:665-7