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Their findings provide conceptual and practical roadmaps for improving the efficacy and reducing toxicity of available medicines. They also offer insights into the biology of T. gondii, suggest critical molecular targets for new medicines, and offer renewed hope for the speedy development of much-needed curative medicines for those with toxoplasmosis–and potentially malaria.

The researchers describe three significant steps forward:

• They characterized a new experimental model, a Brazilian strain of T. gondii, called EGS, which behaves in tissue culture much like the dormant cystic parasites that live in human brain cells. This is “an immensely useful and important advance for medicine development,” said the study’s corresponding author Rima McLeod, professor of ophthalmology and visual sciences and of pediatrics at the University of Chicago. “It allows us to define its genotype and phenotype in depth and to identify what it does to its human host’s blood and primary brain stem cells. Remarkably, this encysted parasite turns on host cell pathways in ways that can alter ribosomal function and cause mis-splicing of transcripts as well as other flaws associated with Alzheimer’s and Parkinson’s disease.”
• The researchers found targets critical for the parasite’s various life stages. Especially appealing was the parasite’s mitochondrial protein, cytochrome b. The team was able to develop compounds more soluble than existing cytochrome b inhibiting quinolones. These can limit parasite survival, and have physiochemical properties commensurate with crossing the blood-brain barrier to treat central nervous system infections. This work emphasizes that the cytochrome bc 1 complex is a critical target. Co-crystallography of the enzyme with the inhibitor provides information to optimize inhibitory compounds.
• They show that greater understanding of T. gondii could have significant implications for anti-malarial research. Compounds they developed were highly effective against Plasmodium falciparum, the parasite that causes malaria, including all tested drug-resistant strains. Malaria, McLeod emphasized, “kills a child every eleven seconds.”

The team’s findings matter because T. gondii is the most frequent cause of infection leading to destruction of the back of the eye for persons in most countries in the world. It is most damaging for infants and children who acquire infection from their mothers during gestation, but it can also cause life-threatening infections in those with compromised immune systems, such as those with cancer, autoimmune disease or AIDS. Highly virulent strains of Toxoplasma are also now known to cause lethal disease, especially in South America.

A large data analysis by researchers at the University of Chicago, published June 26, 2016, in Clinical Infectious Diseases, found that the estimated annual incidence of toxoplasmosis over the last ten years in the US was 6,137 people, based on diagnostic codes for the disease. An editorial in that journal notes that these data “are the strongest to date to indicate that toxoplasmosis represents a significant disease burden in the United States.”

Story Source:

The above post is reprinted from materials provided by University of Chicago Medical Center. Note: Materials may be edited for content and length.

Journal Reference:

1. Martin McPhillie, Ying Zhou, Kamal El Bissati, Jitender Dubey, Hernan Lorenzi, Michael Capper, Amanda K Lukens, Mark Hickman, Stephen Muench, Shiv Kumar Verma, Christopher R. Weber, Kelsey Wheeler, James Gordon, Justin Sanders, Hong Moulton, Kai Wang, Taek-Kyun Kim, Yuqing He, Tatiana Santos, Stuart Woods, Patty Lee, David Donkin, Eric Kim, Laura Fraczek, Joseph Lykins, Farida Esaa, Fatima Alibana-Clouser, Sarah Dovgin, Louis Weiss, Gael Brasseur, Dyann Wirth, Michael Kent, Leroy Hood, Brigitte Meunieur, Craig W. Roberts, S. Samar Hasnain, Svetlana V. Antonyuk, Colin Fishwick, Rima McLeod. New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections. Scientific Reports, 2016; 6: 29179 DOI: 10.1038/srep29179

Ingredient-driven outbreaks make for complex investigations. When a single contaminated ingredient is included in hundreds or even thousands of products, the potential for illness increases exponentially. It becomes extremely challenging to identify the contaminated food. Other ingredient-driven outbreaks that have occurred in recent years include one linked to pine nuts that were used in pesto, salads, and baked goods, and another associated with sunflower seeds found in a variety of trail mixes.

In fact, an ingredient-driven outbreak powered enactment of the FDA Food Safety Modernization Act (FSMA), the first major overhaul of the U.S. food system in 70 years. In 2009, Salmonella-contaminated peanut butter and peanut products sickened more than 700 people and led to nine deaths. According to the Centers for Disease Control and Prevention, nearly 3,000 peanut products — including crackers, cookies, and granola bars produced by a variety of companies — may have been made with the contaminated ingredients produced by the Peanut Corporation of America (PCA). Illnesses spread throughout the country as investigators raced to identify the source of contamination. It took months to pinpoint the tainted products, and to then track down the number of items, retailers, and distributors involved. Meanwhile, people kept getting sick.

The PCA outbreak underscored the importance of a prevention-based approach to foodborne contamination, codified in FSMA. The law requires food manufacturers to take proactive steps to prevent food safety problems. Companies that supply food ingredients must adhere to adequate food safety practices. Manufacturers must develop safety plans for their processing facilities, which identify possible points of contamination and steps to mitigate them, and monitor the effectiveness of those efforts. When problems arise, food processors must work diligently to correct them.

The investigation into contaminated frozen vegetables is ongoing, with both manufacturers and regulators working to protect consumers from further illnesses. The new prevention-based requirements for food-processing facilities will begin to go into effect in September 2016.

See more information at: http://www.cdc.gov/listeria/outbreaks/frozen-vegetables-05-16/index.html