Sex dichotomy in the course of experimental latent toxoplasmosis

Toxoplasma gondii is an opportunistic zoonotic protozoan that exceeds neurological and congenital impact sequence to reactivating latent toxoplasmosis especially under immunosuppression. Sex-associated hormones influence the severity of Toxoplasma infection. Thus, our study aimed to compare toxoplasmosis associated morbidity in both male and female mice and to monitor the response to anti-Toxoplasma therapeutics fortified with sex hormones in comparison to presently used drugs. Twenty male and 20 female mice were infected with ME49 Toxoplasma strain. The morbidity was assessed in the chronic stage in both sexes by estimating brain cyst burden, brain histopathological examination and monitoring serum anti-Toxoplasma IL-12 using ELISA method. Another 40 male and 40 female mice were infected with ME49 Toxoplasma strain then after 6 weeks received different treatment regimens including Atovaquone, Spiramycin, Metronidazole, Estradiol benzoate and Testoserone propionate either as a monotherapy or as a combination. Treatment response was monitored by scoring mice activity and brain cyst burden. This study showed that female mice demonstrated higher cyst burden and manifested more pathological reactions than male mice. While, the IL-12 serum level was significantly higher in male than female mice. Also, it is proved that the Toxoplasma cyst number was reduced significantly when used testosterone/atovaquone, or testosterone/spiramycin/metronidazole combined regimen in female mice groups. While for male mice, the combined therapy of spiramycin/metronidazole was the superior one. Accordingly, combined therapy with sex hormones is a promising strategy for discovering new therapeutic regimens for treating latent toxoplasmosis especially in female. [Display omitted] •Sex proved a variable that influence the course, and the response to treatment of chronic latent toxoplasmosis.•Female mice manifested exaggerated brain pathological lesions, high brain cyst burdens and low serum IL-12 levels.•Male mice manifested a mild brain lesions, lower brain cyst burdens, and higher serum levels of IL-12.•Female mice responded effectively to the anti-Toxoplasma drug-hormone co-therapy, a response which was significant from that of the other tested treatment regimens.•Co-administration of sex hormones with anti-Toxoplasma chemotherapeutics in the treatment of male mice proved no significant advantages over the other tested treatment regimens.