New effective and safe combination therapy for acute and chronic toxoplasmosis in murine models

ABSTRACT

Toxoplasma gondii is a protozoan parasite that infects humans and most species of warm blood animals. The most effective treatment for toxoplasmosis is the classic combination of pyrimethamine/sulfadiazine while the safest drug is spiramycin. These traditional anti-Toxoplasma drugs are either ineffective or have serious side effects that sometimes needs discontinuation of treatment. Both mouse [acute] and rat [chronic] models were used to evaluate a novel dipyridamole/allopurinol anti-Toxoplasma combination therapy that targets the purine salvage pathways of the parasite. The efficacy and safety of the new drugs were evaluated in comparison with traditional therapies; pyrimethamine/sulfadiazine and spiramycin. The life expectancy of mice in dipyridamole/ allopurinol group was significantly increased in comparison to other drug groups and almost doubled in relation to the infection control group. A significant reduction of anti-Toxoplasma antibody titers was only present in dipyridamole/allopurinol group in comparison to the infection control groups in both acute and chronic states of infection. The drug proves to be safe as evidenced by normal blood parameters reflecting no sign of drug toxicity. Pyrimethamine/sulfadiazine combination was second in efficacy while spiramycin was second in safety