Scientists at the Jundiaí Medical School in São Paulo, Brazil, have made significant strides in treating toxoplasmosis, a widespread infectious disease. In their recent study published in PLOS ONE, they screened 160 existing drugs from the COVID Box, a compound library initially developed to combat SARS-CoV-2 by Medicines for Malaria Venture (MMV), a non-profit focused on affordable antimalarial drugs.
The researchers identified six compounds, including ethaverine, almitrine, fluspirilene, thiethylperazine, PB38, and nebivolol, which proved to be at least 30 times more effective against the toxoplasmosis parasite than host cells. Almitrine, typically prescribed for chronic obstructive pulmonary disease (COPD), was particularly promising, showing a significant reduction in brain parasite load when tested on mice with chronic toxoplasmosis. This breakthrough collaboration also involved researchers from the Federal University of Alfenas (UNIFAL) and the Federal University of Paraíba (UFPB).
Experiments
In the laboratory, the COVID Box compounds underwent thorough assessment in human cells infected by Toxoplasma gondii, the protozoan parasite responsible for toxoplasmosis. Additionally, computational analysis was employed to gauge aspects like absorption, distribution, metabolism, excretion, and toxicity.
Juliana Quero Reimão, the lead author of the study, explained that all the selected compounds exhibited favorable traits such as gastrointestinal absorption and the ability to penetrate the blood-brain barrier – a crucial attribute for treating diseases caused by brain-infecting parasites. Their primary goal was to identify compounds capable of entering cells, eradicating the pathogen, and sparing host cells from harm.
While more trials are necessary before repurposing these drugs for toxoplasmosis treatment, the initial findings are highly encouraging. Reimão emphasized that ongoing research would explore additional compounds, which might prove even more effective.
Developing new therapies for toxoplasmosis is imperative due to the limited treatment options, particularly in the acute stage, where existing drugs can lead to hypersensitivity and toxicity. Pregnant women and individuals with chronic toxoplasmosis face limited treatment choices, underscoring the importance of continued research and development.
Toxoplasmosis presents a complex treatment challenge as it progresses in two stages. Although effective drugs are available for the acute phase, they become ineffective in the chronic stage. During the acute phase, the parasite multiplies rapidly, mainly infecting brain, eye, and muscle cells while forming protective cysts. Symptoms then subside, marking the onset of the chronic or latent stage.
The disease becomes perilous if the host’s immune system weakens, potentially leading to severe complications, including cerebral issues that could be fatal. Pregnant women are routinely screened for toxoplasmosis in the first trimester due to the risk of fetal transmission, resulting in congenital toxoplasmosis. Meanwhile, men may remain unaware of their infection unless their immune system becomes compromised.
Human contamination typically occurs through the consumption of contaminated water or food. Congenital toxoplasmosis transmitted during pregnancy can result in miscarriage, birth defects, and various neurological, auditory, and ocular issues. In Brazil, approximately one in three individuals is estimated to have toxoplasmosis, according to the Adolfo Lutz Institute, the primary epidemiological surveillance laboratory for São Paulo state. In the United States, around 40 million adults and children are infected, with toxoplasmosis being the leading cause of death from foodborne diseases, according to the Centers for Disease Control and Prevention (CDC).
Most T. gondii infections are asymptomatic, with some individuals experiencing mild symptoms such as muscle and joint pain, flu-like discomfort, swollen lymph nodes, and fatigue. The highest risk of severe toxoplasmosis is posed to infants born to mothers infected during or shortly before pregnancy and immunocompromised patients, including those undergoing certain chemotherapy treatments, transplant recipients, and individuals with HIV/AIDS. A diagnostic test is advisable for these groups, and if positive, treatment should continue until symptoms improve.
The next steps for the researchers involve assessing the other promising compounds in animal models with toxoplasmosis, both in the acute and chronic phases. They have also screened additional compound libraries supplied by MMV, totaling 600 compounds evaluated.