Measuring the effect of co-administration of FDA-approved drugs against chronic stage Toxoplasma gondii
Advisor Information
Paul Davis
Location
UNO Criss Library, Room 249
Presentation Type
Oral Presentation
Start Date
4-3-2016 9:15 AM
End Date
4-3-2016 9:30 AM
Abstract
Toxoplasma gondii is an intracellular obligate parasite that affects nearly half the world’s population. Humans can be infected via improper handling of feline feces, consuming undercooked or raw meat, blood transfusion, or may be infected congenitally from an infected mother. T. gondii has two stages of infection: the acute, quickly multiplying tachyzoite stage, and the chronic, slowly dividing bradyzoite stage. The acute stage is quickly subdued by the host’s immune system (provided it is not compromised). However, by this time T. gondii will have formed cysts in the brain which remain throughout the host’s lifetime. This stage of the infection is known as the chronic stage, which currently has no known treatment. Immunocompromised individuals are especially at risk of developing symptoms as the infection can be active again, in the absence of an effective immune response. Eradicating the cysts will effectively cure T. gondii and significantly reduce the likelihood of developing symptoms. Current efforts in finding a cure for the chronic infection involve finding a cocktail of novel drugs that work synergistically to effectively clear T. gondii from the host. However, this is limited by poor brain penetration and high toxicity of several novel drugs. A combination of drugs including metronidazole, pyrimethamine, and sulfadiazine displayed synergistic effects with a significant reduction in cyst burden at concentrations of 120 mg/kg, 12.5 mg/kg, and 400 mg/kg, respectively, in vivo mice.
Measuring the effect of co-administration of FDA-approved drugs against chronic stage Toxoplasma gondii
UNO Criss Library, Room 249
Toxoplasma gondii is an intracellular obligate parasite that affects nearly half the world’s population. Humans can be infected via improper handling of feline feces, consuming undercooked or raw meat, blood transfusion, or may be infected congenitally from an infected mother. T. gondii has two stages of infection: the acute, quickly multiplying tachyzoite stage, and the chronic, slowly dividing bradyzoite stage. The acute stage is quickly subdued by the host’s immune system (provided it is not compromised). However, by this time T. gondii will have formed cysts in the brain which remain throughout the host’s lifetime. This stage of the infection is known as the chronic stage, which currently has no known treatment. Immunocompromised individuals are especially at risk of developing symptoms as the infection can be active again, in the absence of an effective immune response. Eradicating the cysts will effectively cure T. gondii and significantly reduce the likelihood of developing symptoms. Current efforts in finding a cure for the chronic infection involve finding a cocktail of novel drugs that work synergistically to effectively clear T. gondii from the host. However, this is limited by poor brain penetration and high toxicity of several novel drugs. A combination of drugs including metronidazole, pyrimethamine, and sulfadiazine displayed synergistic effects with a significant reduction in cyst burden at concentrations of 120 mg/kg, 12.5 mg/kg, and 400 mg/kg, respectively, in vivo mice.