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Abstract The Ultimate Goal Of This Study Was To Evaluate The Anti-Toxoplasmic Effect Of The Anticancer Drug Miltefosine, Both In-Vitro And In-Vivo. The Impact Of Using This Drug Was Evaluated And Compared With Those Of The Standard Therapy Co-Trimoxazole, Clindamycin And Their Combinations, On Three Main Aspects: I) The Parasitic Load In Different Organs, Using Quantitative Real Time-PCR (Qpcr) Assay Targeting The B1 Gene Of Toxoplasma Gondii; Ii) The Levels Of Toxoplasma Igg, Igm, TNF- Alfa, IL-12 And Interferon Gamma Releasing Assay (IGRA) In Infected Treated And Un-Treated Mice; Iii) The Ultrastructure Changes Imported On The Intracellular And Extracellular Tachyzoites On Infected Treated Vero Cells. It Was Found That Miltefosine Was Not Toxic To Vero Cells At 0.6 Mg/Ml (1.5 Μm) And Showed The Highest Activity Against The Free Parasite In-Vitro, Causing 50% Reduction Of Initial Tachyzoite Numbers After 7 Hours Of Treatment. Both Intraperitoneal (IP) And Subcutaneously (SC) Administered Miltefosine Induced A Significant Increase In TNF-Α, As Well As The Anti-Toxoplasma Igg And Igm Antibodies, IL-12 With A Significant Reduction In IGRA As Compared To The Control group (P<0.01). Despite Having A Suppressive Effect On Tachyzoites Viability In-Vitro, The Drug Tested Failed To Reduce, And Even Increased, The Parasite Load In Different Tested Animal Tissues Of The Infected Mice. The Finding Of A Consistently Higher Parasite Load In The Miltefosine Treated Mice Than The Infected Untreated Control Was In Contrary To The Effect Observed With Co-Trimoxazole, In Which The Load Was Generally Lower Than The Control Group. On Incubation Of Miltefosine With Tachyzoites-Infected Vero Cells, Marked Ultrastructural Changes Were Observed Only On The Extracellular Located Tachyzoites Within A Limited Time Frame (5 Hours).Conclusion; Miltefosine Appears To Be A Good Candidate For Combination Therapy For Toxoplasma, At Least To Combat The Extracellular Parasite And To Immunomodulate The Host Response. Additional Studies With Several Anti-Toxoplasma Combinations And A Number Of Drug Delivery Systems Are Warranted. |