Toxoplasmosis is a global disease caused by an obligatory intracellular protozoan “Toxoplasma gondii “(T. gondii). It is estimated that around one-third of the world's population is infected with toxoplasmosis including more than 13 million HIV infected patients, causing brain inflammation and other illnesses (Salas-Lais et al., 2020). Toxoplasmosis is commonly asymptomatic with a latent phase in healthy people while in immunodeficient persons, it can cause severe complications. In pregnant women, congenital anomalies in infants. Also, neurological disorders in HIV infected patients which end up with death (Özcel and Ozbel, 2007; Mesquita et al., 2010). Cerebral toxoplasmosis has emerged as a major CNS problem among acquired immunodeficiency syndrome (AIDS) patients (Nacher et al., 2020), particularly in places with a high prevalence of HIV infection and limited access to highly active antiretroviral therapy (HAART). Most immunocompromised people like AIDS, solid-organ and stem-cell transplant patients inhabiting the developing world usually do not undergo to the anti-Toxoplasma therapy So, the influence of toxoplasmosis is predictable in such patients due to immunosuppression (Mulanovich et al., 2011).

The existing therapy for toxoplasmosis displays many drawbacks such as dihydrofolate reductase (DHFR) inhibitors like pyrimethamine (PYR). They are the most common chemical treatments used for T. gondii infection. These drugs only work on tachyzoites, not bradyzoites. Furthermore, when administered as single agents, they are ineffective. As a result, they're frequently used with sulfa drugs (Rosowsky et al., 1998). One of the important issues in the treatment of chronic T. gondii infection is poor brain penetration of standard treatments. Sulfadiazine and PYR combination were found to be effective against acute toxoplasmosis (Israelski and Remington, 1993), but not against chronic cerebral toxoplasmosis (Faucher et al., 2011). Furthermore, long-term usage of these medications can result in haematological and renal damage (Crespo et al., 2000). Spiramycin is an antibiotic that belongs to the macrolide family and has anti-parasitic effects. Streptomyces ambofaciens produces it, and it's the drug of choice for treating T. gondii during pregnancy. Congenital toxoplasmosis and vertical transmission are reduced by this drug (Peyron et al., 2017). Valentini et al. (2015) investigated the Spiramycin/Cotrimoxazole (Sp/C) combination and discovered that it is effective in preventing toxoplasmosis transfer from mother to fetus. In a mouse model of chronic toxoplasmosis, spiramycin was found to be effective when combined with other therapies such as metronidazole. The combination of spiramycin and metronidazole therapy resulted in enhanced spiramycin absorption in the brain and nearly full elimination of brain cysts (Chew et al., 2012).

The immune system plays a vital role in the protection of the host against foreign antigens and parasitic infections (Page et al., 2014). The complex protective immune response against T. gondii and other intracellular parasites necessitates the interaction of innate immunity, humoral immunity, and cellular acquired immunity, which is directed against the parasite's several stages (Mévélec et al., 2020). The ability of CD4+ and CD8+ T cells to produce IFN-γ depends mostly on the appropriate adaptive immune response (Sasai and Yamamoto, 2019). Antibodies also participate in defense, alongside with T cells (KangRemington and Suzuki, 2000).

Immunomodulators like levamisole (LEVA) are biotic mediators that enhance the defense mechanism against infectious diseases (Agrawal et al., 2010). LEVA is a broad-spectrum tetrahydro-6-phenylimidazo-thiazole antihelminthic drug and is immunoregulatory too. Its possible immuno-regulatory role is referred to its mimicry of the thymic hormone. Thymopoietin influences several components of the immune system as well as the stimulation of phagocytosis and regulatory T cells to restore homeostasis in a disturbed immune system. LEVA can increase macrophage chemotactic effect and T lymphocyte function. It has been used to treat a variety of dermatologic conditions including skin infections, cancer, and viral infections like AIDS (Mitchell, 2003; Zhai et al., 2007). It also can modify the immune system by resetting the immunological balance towards Th1 response (Mitchell, 2003). LEVA has also been shown to enhance serum complement activity and leukocyte functions, such as lymphocyte phagocytosis and/or lymphokine synthesis (Mulero et al., 1998) in addition to stimulation of cytokines like interferon (IFN), interleukin (IL) 6, IL12, IL18, and IL1 (Chen et al., 2008). Therefore, in the present study, we investigated spiramycin alone and/or in combination with levamisole in experimental T. gondii infection.