Toxoplasma gondii, the causative agent of toxoplasmosis, is a parasitic protozoan that infects almost a third of the global population. In cases of profound and prolonged immunosuppression, reactivation of the infection occurs in chronically infected individuals, which can be life-threatening. RT is a particularly devastating complication in allogeneic hematopoietic stem cell transplant recipients, the fastest growing population of immunosuppressed patients in Europe. Despite this, there are still no guidelines for the diagnosis and treatment of RT. Moreover, the limited therapeutic options for RT are not only inadequate for allogeneic hematopoietic stem cell transplant recipients due to pronounced myelotoxicity, but also ineffective because they only treat circulating parasites. The ToxoReTREAT project is aimed at solving the problem of RT in this patient population by applying a multidisciplinary approach in providing new therapeutic options, with potentially improved efficiency and reduced side effects, and formulating national guidelines for the diagnosis and treatment of RT.
The ToxoReTREAT project will offer new, improved approaches to the diagnosis and treatment of reactivated toxoplasmosis (RT) in the growing population of allogeneic hematopoietic stem cell transplant recipients. Through the multidisciplinary approach, we will develop national guidelines for the diagnosis and treatment of RT, examine the efficacy of newly synthesized acridine and acridone derivatives in experimental models of RT, and analyze the experimental results by using the freely available ImageJ software for computer analysis.
The main goal of the ToxoReTREAT project is to solve the problem of reactivated toxoplasmosis (RT) in the population of allogeneic hematopoietic stem cells transplant recipients by applying a multidisciplinary approach (medicine, pharmaceutical chemistry, computer science) to offer cost-benefit improvements in the management of RT and efficient novel treatment options.
Molecular monitoring of RT, isolation and characterization of T. gondii strains, identification of risk factors and evaluation of the effectiveness of standard treatment options will result in the formulation of National Guidelines for the diagnosis and treatment of toxoplasmosis in allogeneic hematopoietic stem cell transplant recipients. Acridine and acridone derivatives, newly synthesized and modified during this project, will be tested in in vitro and in vivo experimental models of RT, using T. gondii strains isolated from patients diagnosed with RT. Our research will identify at least one RT drug candidate with reduced toxicity and increased overall efficacy against T. gondii tachyzoites and bradyzoites, compared to standard treatment. We expect that the results of our project will raise the interest of the pharmaceutical industry to engage in the development of new and better drugs for the treatment of toxoplasmosis. The application of the freely available ImageJ software for the improvement of the automated evaluation of the results of chemotherapy experiments will contribute to the sustainable transfer of knowledge acquired through chemotherapy experiments.
The National Reference Laboratory (NRL) for toxoplasmosis is recognized in the professional community throughout the region as the only center that performs isolation and genotyping of T. gondii strains and chemotherapy experiments using in vitro and in vivo models for infections caused by T. gondii and Plasmodium sp.. Therefore, ToxoReTREAT will stimulate further long-term regional cooperation generated by the participation of representatives of the regional scientific community at our workshop and final conference, with the perspective of creating a multicenter study, allowing us access to a wider range of clinical samples on the one hand and on the other hand, re-affirming the position of our NRL as the leading regional center in this area. At the international level, the results of the project are expected to further improve the position of NRL within the European network of reference laboratories for toxoplasmosis and other parasitic diseases. Dissemination of the results of the ToxoReTREAT project, carried out at the international congresses, will expand the research perspectives of IMR, MFUB, FPHUB and IPB, which will lead to strengthening our current position and enabling the sustainable growth of each SRO participating in the project.
At the local level, the ToxoReTREAT project will provide much-needed National Guidelines for the diagnosis, monitoring and treatment of toxoplasmosis in hematopoietic stem cell transplant recipients. The project will also provide advanced training in sophisticated methodologies for the three young researchers involved, such as in vitro maintenance of T. gondii strains, as well as in vitro bradyzoite-tachyzoite conversion (two PhD students at IMR) and detailed computer analysis of experimental photographs (one PhD student at IPB), thus improving their professional capacity.
The strength of the ToxoReTREAT project is reflected in the professional capacity of the project team members. The leading SRO is the Institute for Medical Research (IMR) of the University of Belgrade, and the project leader (Tijana Štajner, MD/PhD, senior research associate, specialist in medical microbiology, head of the NRL for toxoplasmosis) and 4 members of the project team ( Jelena Srbljanović, PhD, research associate; Branko Bobić, MD/PhD, principal research fellow; Olivera Lijeskić, MD, research assistant, PhD student at MFUB and Đorđe Zlatković, MPharm, junior research assistant, PhD student at FPHUB). In addition to IMR, the project participants are Dragana Vujić, MD/PhD, full professor, specialist in pediatrics, subspecialist in hematology, head of the Center for Hematopoietic Stem Cell Transplantation at the Institute for Maternal and Child Health of Serbia “Dr. Vukan Čupić”, from the MFUB SRO, Vladimir Dobričić, PhD, associate professor, from the FPHUB, and Anđelija Ilić, PhD, principal research fellow, and Jelena Trajković, research assistant, doctoral student at the Faculty of Physics, UB, both from the IPB.
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