Modulation of haematological and pathological changes caused by toxoplasma gondii in an experimental model of chronic infection

Wide spectrum of pathologic patterns is encountered in T. gondii infection, ranging from trivial pathology to fatal disease. The study was done to evaluate the ability of some drug groups to reverse the pathological changes caused by T. gondii infection. This evaluation was done, in vivo, in a rat model of chronic infection parallel to that in human. Lung, liver and brain specimens were taken in definite time points respecting the kinetics of infection in that model. Blood counts were done to all groups to evaluate efficacy and toxicity of drugs. A new combination of dipyridamole/ allopurinol was able to significantly reduce the pathology in all organs to almost the baseline pathology of chronic Toxoplasma infection. The relatively moderate protective effect of pyrimethamine/sulfadiazine combination was undermined by the toxic effects evidenced by pathology and haematological parameters. Spiramycin, in spite of proving safe, yet its protective effective is relatively weak in all organs especially in the brain where it seems to offer no protection

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

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