Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

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.

Long-term Ocular Outcomes in Congenital Toxoplasmosis Treated Perinatally.

BACKGROUND: Congenital toxoplasmosis (CT) can be accompanied by serious organ manifestations, particularly retinochoroiditis, and may occur throughout life. We aimed to monitor long-term ocular prognosis in a large French cohort of patients with CT and its changes over time in the context of mandatory prenatal screening (since 1992) and incidence decrease since 2008. METHODS: Patients with CT diagnosed between 1987 and 2021 were prospectively included and followed for up to 35 years. The effect of the period of conception on the risk of first retinochoroiditis has been tested using a flexible extension of the Cox model. Incidence rates of retinochoroiditis were estimated. RESULTS: A total of 646 infected live born children were followed for a median of 12 years (range, 0.5-35); 187 patients (29%) had at least 1 ocular lesion (first at a median age of 5 years; range, 0-26 years) with peaks at 7 and 12 years. Early maternal infection and the presence of nonocular signs at birth were associated with a higher risk of retinochoroiditis, whereas delayed diagnosis of CT (after birth versus before or at birth) was associated with a lower risk (13% decrease for each additional month after birth; P = .01). A period effect for the risk of developing retinochoroiditis in patients born after 2008 was not detected. CONCLUSIONS: Despite prenatal screening and prolonged perinatal treatment, retinochoroiditis is not a rare event in French patients with CT and can occur well into adulthood, with peak incidences at 7 and 12 years of age. It rarely causes severe damage but warrants regular follow-up into adulthood.