Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.
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ABSTRACT:
SUBMITTER: Zhou Y
PROVIDER: S-EPMC10168490 | biostudies-literature | 2023 May
REPOSITORIES: biostudies-literature
Publications
Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.
Zhou Y Y Leahy K K Grose A A Lykins J J Siddiqui M M Leong N N Goodall P P Withers S S Ashi K K Schrantz S S Tesic V V Abeleda A P AP Beavis K K Clouser F F Ismail M M Christmas M M Piarroux R R Limonne D D Chapey E E Abraham S S Baird I I Thibodeau J J Boyer K K Torres E E Conrey S S Wang K K Staat M A MA Back N N Gomez Marin J J Peyron F F Houze S S Wallon M M McLeod R R
medRxiv : the preprint server for health sciences 20230510
<h4>Background</h4>Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide.<h4>Methods/findings</h4>In our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall ...[more]
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Project description:ObjectiveTo determine a cost-minimizing option for congenital toxoplasmosis in the United States.Methodology/principal findingsA decision-analytic and cost-minimization model was constructed to compare monthly maternal serological screening, prenatal treatment, and post-natal follow-up and treatment according to the current French (Paris) protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. One- and two-way sensitivity analyses are used to evaluate robustness of results. Universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French protocol, is found to be cost-saving, with savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, and to bivariate analysis of test costs and incidence of primary T. gondii infection in pregnancy. Given the parameters in this model and a maternal screening test cost of $12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. If universal testing generates economies of scale in diagnostic tools-lowering test costs to about $2 per test-universal screening is cost-saving at rates of congenital infection well below the lowest reported rates in the United States of 1 per 10,000 live births.Conclusion/significanceUniversal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities.
| S-EPMC3181241 | biostudies-literature
Project description:AimsTo determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern).Materials and methodsWe collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain) to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life.Results61 positive samples for specific IgM (0.39%) and 9 positives for IgA (0.5%) were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality). A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city.ConclusionsIncidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis.
| S-EPMC3104965 | biostudies-literature
Project description:BackgroundPrimary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario.Methodology/principal findingsWe retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years.Conclusions/significanceCost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants.
| S-EPMC5503164 | biostudies-literature
Project description:BackgroundCongenital Toxoplasmosis (CT) can have severe consequences. France, Austria, and Slovenia have prenatal screening programs whereas some other countries are considering universal screening to reduce congenital transmission and severity of infection in children. The efficiency of such programs is debated increasingly as seroprevalence among pregnant women and incidence of congenital toxoplasmosis show a steady decrease. In addition, uncertainty remains regarding the effectiveness of pre- and postnatal treatments.MethodTo identify cost-effective strategies, prenatal and neonatal screenings were compared using a decision-analytic model based on French guidelines and current knowledge of long-term evolution of the disease in treated children. Epidemiological data were extracted from the scientific literature and clinical data from the French Lyon cohort. Strategies were compared at one year of age, when infection can be definitively evaluated, and at 15 years of age, after which validated outcome data become scarce. The analysis was performed from the French Health Insurance System perspective and included direct medical costs for pregnant women and their children.ResultsThe 1-year Incremental Cost-Effectiveness Ratio showed that prenatal screening would require investing €14,826 to avoid one adverse event (liveborn with CT, fetal loss, neonatal death or pregnancy termination) compared to neonatal screening. Extra investment increased up to €21,472 when considering the 15-year endpoint.ConclusionsPrenatal screening is cost-effective as compared to neonatal screening in moderate prevalence areas with predominant Type II strains. In addition, prenatal screening, by providing closer follow-up of women at risk increases the number of occasions for education avoiding toxoplasmosis.
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Project description:PURPOSE:To determine the incidence and natural history of cataracts in children with congenital toxoplasmosis. METHODS:Children referred to the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981 and 2005 were examined by ophthalmologists at predetermined times according to a specific protocol. The clinical course and treatment of patients who developed cataracts were reviewed. RESULTS:In the first year of life, 134 of 173 children examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present at birth and 13 developed postnatally. Locations of the cataracts included anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen cataracts were partial, nine total, and five with unknown complexity. Twelve cataracts remained stable, 12 progressed, and progression was not known for 3. Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma. Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with cataracts had additional ocular lesions. CONCLUSIONS:In the NCCCTS cohort, 11.6% of patients were diagnosed with cataracts. There was considerable variability in the presentation, morphology, and progression of the cataracts. Associated intraocular pathology was an important cause of morbidity.
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Project description:The CRISPR system has become a powerful biological tool with a wide range of applications. However, improving targeting specificity and accurately predicting potential off-targets remains a significant goal. Here, we introduce a web-based CR: ISPR/Cas9 O: ff-target P: rediction and I: dentification T: ool (CROP-IT) that performs improved off-target binding and cleavage site predictions. Unlike existing prediction programs that solely use DNA sequence information; CROP-IT integrates whole genome level biological information from existing Cas9 binding and cleavage data sets. Utilizing whole-genome chromatin state information from 125 human cell types further enhances its computational prediction power. Comparative analyses on experimentally validated datasets show that CROP-IT outperforms existing computational algorithms in predicting both Cas9 binding as well as cleavage sites. With a user-friendly web-interface, CROP-IT outputs scored and ranked list of potential off-targets that enables improved guide RNA design and more accurate prediction of Cas9 binding or cleavage sites.
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Project description:BackgroundToxoplasma gondii is one of the world's most common parasites. Primary infection of the mother during pregnancy can lead to transmission to the fetus with risks of brain and eye lesions, which may cause lifelong disabilities. France instituted a national program based on monthly retesting of susceptible pregnant women to reduce the number of severe cases through prompt antenatal and postnatal treatment and follow-up.ObjectiveTo evaluate the ability of the French prenatal retesting program to reduce the lifetime costs of congenital toxoplasmosis.MethodsWe measured and then compared the costs and benefits of screening vs. not screening using decision-tree modelling. It included direct and indirect costs to society of treatment and care, and the lifetime lost earnings of children and caregivers. A probabilistic sensitivity analysis was carried out.FindingsTotal lifetime costs per live born child identified as congenitally infected were estimated to be €444 for those identified through prenatal screening vs €656 for those who were not screened. Estimates were robust to changes in all costs of diagnosis, treatment, and sequelae.InterpretationScreening for the prevention of the congenital T. gondii infection in France is cost saving at €212 per birth. Compared with no screening, screening every pregnant woman in France for toxoplasmosis in 2020 would have saved the country €148 million in addition to reducing or eliminating the devastating physical and emotional suffering caused by T. gondii. Our findings reinforce the conclusions of other decision-analytic modelling of prenatal toxoplasmosis screening.
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Project description:From a prospective cohort of 344 women who seroconverted for toxoplasmosis during pregnancy, 344 amniotic fluid, 264 placenta, and 216 cord blood samples were tested for diagnosis of congenital toxoplasmosis using the same PCR assay. The sensitivity and negative predictive value of the PCR assay using amniotic fluid were 86.3% and 97.2%, respectively, and both specificity and positive predictive value were 100%. Using placenta and cord blood, sensitivities were 79.5% and 21.2%, and specificities were 92% and 100%, respectively. In addition, the calculation of pretest and posttest probabilities and the use of logistic regression allowed us to obtain curves that give a dynamic interpretation of the risk of congenital toxoplasmosis according to gestational age at maternal infection, as represented by the three sample types (amniotic fluid, placenta, and cord blood). Two examples are cited here: for a maternal infection at 25 weeks of amenorrhea, a negative result of prenatal diagnosis allowed estimation of the probability of congenital toxoplasmosis at 5% instead of an a priori (pretest) risk estimate of 33%. For an infection at 10 weeks of amenorrhea associated with a pretest congenital toxoplasmosis risk of 7%, a positive PCR result using placenta at birth yields a risk increase to 43%, while a negative result damps down the risk to 0.02%. Thus, with a molecular diagnosis performing at a high level, and in spite of the persistence of false negatives, posttest risk curves using both negative and positive results prove highly informative, allowing a better assessment of the actual risk of congenital toxoplasmosis and finally an improved decision guide to treatment.
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