Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more
Authors: Zhou Ying , Leahy Karen , Grose Andrew , Lykins Joseph , Siddiqui Maryam , Leong Nicole , Goodall Perpetua , Withers Shawn , Ashi Kevin , Schrantz Stephen , Tesic Vera , Abeleda Ana Precy , Beavis Kathleen , Clouser Fatima , Ismail Mahmoud , Christmas Monica , Piarroux Raphael , Limonne Denis , Chapey Emmanuelle , Abraham Sylvie , Baird Isabelle , Thibodeau Juliette , Boyer Kenneth M. , Torres Elizabeth , Conrey Shannon , Wang Kanix , Staat Mary Allen , Back Nancy , L’Ollivier Coralie , Mahinc Caroline , Flori Pierre , Gomez-Marin Jorge , Peyron Francois , Houzé Sandrine , Wallon Martine , McLeod Rima 
Published: May 2024

Background
Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide.

Objectives
We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory.

Methods
Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology.

Findings
ICT was compared with gold-standard or predicate-tests. Overall, ICT performance for 1093 blood/4967 sera was 99.2%/97.5% sensitive and 99.0%/99.7% specific. However, in clinical trial, FDA-cleared-predicate tests initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon’s Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false-positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO REASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening.

Conclusions/significance
This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories.

Trial registration
NCT04474132, https://clinicaltrials.gov/study/NCT04474132
ClinicalTrials.gov