Introduction: Although miltefosine is the first line for treatment of leishmaniasis, it could have multiple un-recognized effects if any infection accidentally takes place during therapy. The aim is to precisely evaluate the molecular and biochemical remarks of miltefosine on Toxoplasma gondii accidental infection during miltefosine therapeutic course. Methodology: changes implied by miltefosine daily parenteral administration to Toxoplasma-infected mice, subcutaneously or intraperitoneal, have been investigated. Tumor necrosis factor-Alfa, immunoglobulin G and M, IL-12 and interferon-gamma release assay (IGRA) were measured in the animals’ sera post-miltefosine administration in addition to monitoring Tissue parasite load by measuring the daily changes of copy number of B1 gene using quantitative PCR technique (qPCR). Results: Miltefosine significantly increased inflammatory and immunological markers (TNF-α, IgG and IgM) measured on reference to control untreated group, with a significant increase in the parasite burden and distribution in all tested organs (F = 390.9, df = 9, P < 0.0001), (F = 4478.98, df = 4.75, P< 0.0001) and (F = 247.3, df = 4, P < 0.0001); heart, liver and lung, respectively, using MANOVA. Releasing capability of macrophages significantly increased during the first day of infection, however, it finally declined after seven consecutive doses of miltefosine (t = 7.96, P < 0.001). Conclusion: Miltefosine could not control the pathogenesis and multiplication of accidental Toxoplasma infection. Cumulative low parenteral daily doses of miltefosine (1.5 µM) could inversely affected the normal humoral immunity against toxoplasmosis. Therefore, a periodical screening for accidental Toxoplasma infection during the course of therapy is strongly recommended.

Conclusion:MSCs have an antiinflammatory effect and prolong the survival of T. gondii infected mice; however, they have a non-significant effect on brain cyst count.El-Hosseiny et al., Afro-Egypt J Infect Endem Dis 2020;10(2):129-140 https://aeji.journals.ekb.eg/

Background: Standard therapies for toxoplasmosis have serious adverse effects and can't eliminate the cyst stage of chronic infection. Highly effective medications with few adverse effects are required. This work aimed to determine the efficacy of nitrofurantoin in the treatment of chronic toxoplasmosis as a means of overwhelming the limitations of other standard medications. Methods: A total of 42 laboratory-bred Swiss female albino mice were included. Six mice were left in the non-infected, non-treated group (G 1). The rest (12mice/ each group) were experimentally infected orally with the T. gondii strain (ME49). Six weeks post-infection the experimental mice were divided into four groups.Group1:uninfected, untreated; Group2:infected, untreated mice (infected control); Group3:infected treated mice with nitrofurantoin for two weeks and Group 4: infected mice treated with a combination of nitrofurantoin and spiramycin for two weeks. Sixty days after infection, all mice were slaughtered. Parasitological (brain cyst count) and histological (using hematoxylin and eosin) measures were used to assess the therapeutic impact of nitrofurantoin in chronically infected mice (H & E). Results: High significant reduction of mean brain cyst count was observed in the nitrofurantoin monotherapy group in comparison with the infected control group. The combination-treated group had the best treatment efficacy, with the highest rates of brain cyst decrease. Histopathological studies of the brain tissues showed an obvious correlation with the results of the brain cyst counts. Conclusions: Nitrofurantoin is a possible anti-T.gondii option for clinical usage in chronic toxoplasmosis, as it enhances the antitoxoplasmic effect of standard toxoplasmosis treatment.