An inexpensive, accurate test that detects infections with the parasite Toxoplasma gondii can provide results within 30 minutes from a finger-prick in a doctor’s office or within an hour from a small blood sample tested in a local medical laboratory. The new test can also identify false positives in other types of commercial diagnostic tests for toxoplasmosis, providing swift reassurance to uninfected pregnant women and their doctors and facilitating timely interventions to protect a fetus against toxoplasmosis in acutely infected pregnant mothers.
These findings appear in a study, led by toxoplasmosis specialist Rima McLeod, MD, Professor of Ophthalmology and Visual Science and Pediatrics at the University of Chicago, published May 23, 2024, in PLOS Neglected Tropical Diseases.
"By using this approach and test to monitor pregnant women monthly for Toxoplasma infections, beginning before or very early in pregnancy, we can help prevent infections of their babies," said McLeod. "This test can also contribute to solving the problem of false positives from other Toxoplasma tests, inexpensively, which can help reassure pregnant women and their doctors."
Early detection of T. gondii in previously uninfected pregnant women is key to limiting the damage of toxoplasmosis in unborn babies.
"Without proper diagnosis and medications, acute toxoplasmosis in the fetus can be lethal or lead to premature birth," said co-corresponding author Martine Wallon, MD, of the Institut des agents infectieux and Hôpital de la Croix-Rousse in France. "In newborns, it can cause microcephaly, hydrocephalus, damage and inflammation in the brain, heart, lungs and eyes, and enlargement of the liver and spleen.”
Prompt diagnosis and treatment can also eliminate brain damage, according to co-author Jorge Gómez-Marín of the University of Quindio in Colombia.
Developed by LDBIO Diagnostics of Lyon, France, and as found by the authors, the Toxoplasma ICT IgG-IgM point-of-care diagnostic test provides rapid results on immuno-chromatographic paper, similar to the color-changing tests used in Covid tests. The researchers note that starting as early as possible, uninfected women should have their antibody status tested once a month during pregnancy, beginning before the 12th week and then 4 to 6 weeks after delivery.
The research analyzes 12 new individual studies conducted by scientists in the United States, France and Colombia. Researchers examined the feasibility of using the ICT in multiple clinical circumstances and types of medical care as well as how it was perceived by patients, families and front-line health care workers.
"The ICT and gestational screening are well-received by patients, providers and policy makers, suggesting it may become a valuable part of standard obstetrical practice," McLeod said.
They also sought to use the ICT as a back-up diagnostic tool to detect false positive tests in standard commercial tests for IgM antibodies.
The paper includes collation of the new, previously unpublished research with earlier studies from the University of Chicago, Stanford University and the Palo Alto Medical Foundation in the US, France, Morocco and Tunisia, revealing the test to be more than 97.5% (blood), 99% (serum) sensitive and 100% specific on a large scale and in multiple countries and settings. Scientists tested the serum or blood samples of more than 5,500 individuals in conjunction with more than 20,000 separate assays using reference laboratory comparator tests. The ICT out-performed other non-specialty reference laboratory tests across the studies and proved it could be used to correct the errors of other commercially-available screening tests.
Previous research in 2017 and 2018 provided the proof of principle studies demonstrating that the ICT could perform accurately with serum and whole blood.
Although eight states require the reporting of toxoplasmosis cases to the CDC, doctors in the U.S. do not yet routinely test for T. gondii in pregnant women. In France and Austria, screening for toxoplasmosis during pregnancy has proven to be cost effective; an earlier study calculated similar benefits for the U.S.
The $4 to $10 test meets all the World Health Organization ASSURED criteria and is already being used in Europe and other countries including Martinique, French Guiana and Morocco. The lack of screening in the U.S is partly due to the problems this study resolves, although additional educational programs are needed because of the misperception that the infection is unpreventable and untreatable. In 2018, a randomized, evidence-based, prospective controlled trial in France demonstrated the efficacy of prompt treatment to prevent transmission and complications and the importance of rapid diagnosis and treatment.
“Testing should be supervised by a knowledgeable health care provider because understanding the implications of the results requires medical knowledge of this disease and its treatment," McLeod said. "Proper use is critical since lifelong consequences of this infection are so significant for a family.”
Toxoplasma spreads in the environment from parasites that initially develop in cat intestines and are excreted in cat feces, thereby contaminating soil, water and food. The parasite can also be ingested by eating undercooked meat. Epidemics of infection of highly virulent new strains are occurring in North and Latin America in humans and wildlife. The investigators demonstrated that this new test is efficient and useful for epidemiologic studies.
Once the microscopic, single-celled T. gondii establishes itself in the human body, it makes its way to the brain where it survives life-long in a latent stage that currently is untreatable. Roughly two billion people harbor this parasite in their brains, and scientists are discovering that the parasite may cause or exacerbate illnesses not previously recognized as associated with this infection. Toxoplasmosis can cause headaches, seizures, breathing problems and brain and eye damage in immuno-compromised patients; reactivated, previously dormant parasites can be lethal.
McLeod hopes that by identifying women who are seronegative before pregnancy and diagnosing acute toxoplasmosis promptly in women who are pregnant, U.S. physicians can rapidly treat the infection before it's transmitted to the fetus. The test is also useful in practices such as ophthalmology, where the parasite is the most frequent cause of infection leading to destruction of the back of the eye, and neurology, where T. gondii cause epilepsy and other types of brain damage.
Researchers are seeking approval of the test by the Food and Drug Administration and Clinical Laboratory Improvement Amendments program. The Chicago investigators consider the test as part of a toolbox, along with their work developing novel medicines and vaccines to treat and prevent the infection.
Funding for "Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more" came from a Medical Student Award from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Allergy, Immunology and Infectious Diseases, National Institutes of Health, the A.K. Thrasher Children's Charity Research Fund, the Kiphart Global-Local Health Seed Fund Award, the Taking Out Toxo Foundation, the Toxoplasmosis Research Institute, the Network for Good, the University of Chicago Provost’s Award for Latin America and the Caribbean, the Cornwell Mann Family Foundation and the Rodriguez, Morel, Taub, Rooney, Tirado, Samuel, Drago, Van Dusen, Kapnick, Engel, Kehoe and Mussilami families.
Additional authors include Ying Zhou, Karen Leahy, Andrew Grose, Joseph Lykins, Maryam Siddiqui, Nicole Leong, Perpetua Goodall, Shawn Withers, Kevin Ashi, Stephen Schrantz, Vera Tesic, Ana Abeleda, Kathleen Beavis, Fatima Clouser, Mahmoud Ismail, Monica Christmas, Isabelle Baird and Juliette Thibodeau from the University of Chicago; Raphael Piarroux and Denis Limonne from LDBIO Diagnostics; Emmanuelle Chapey and François Peyron from Institut des agents infectieux, Hôpital de la Croix-Rousse, Lyon, France; Sylvie Abraham and Sandrine Houze from Hôpital Bichat-Claude Bernard, Laboratory of Parasitology, Paris, France; Kenneth Boyer from Rush Presbyterian Hospital and Medical Center; Elizabeth Torres from the University of Quindio, Colombia; Shannon Conrey, Kanix Wang, Mary Allen Staat and Nancy Back from the University of Cincinnati; Corinne L’Ollivier from Aix-Marseille University, France; and Caroline Mahinc and Pierre Flori from University Hospital of Saint-Étienne, France.
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