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.

Multicenter evaluation of the Toxoplasma gondii Real-TM (Sacace) kit performance for the molecular diagnosis of toxoplasmosis.

The molecular detection of Toxoplasma gondii DNA is a key tool for the diagnosis of disseminated and congenital toxoplasmosis. This multicentric study from the Molecular Biology Pole of the French National Reference Center for toxoplasmosis aimed to evaluate Toxoplasma gondii Real-TM PCR kit (Sacace). The study compared the analytical and clinical performances of this PCR assay with the reference PCRs used in proficient laboratories. PCR efficiencies varied from 90% to 112%; linearity zone extended over four log units (R2 > 0.99) and limit of detection varied from 0.01 to ≤1 Tg/mL depending on the center. Determined on 173 cryopreserved DNAs from a large range of clinical specimens, clinical sensitivity was 100% [106/106; 95 confidence interval (CI): 96.5%-100%] and specificity was 100% (67/67; 95 CI: 94.6%-100%). The study revealed two potential limitations of the Sacace PCR assay: the first was the inconsistency of the internal control (IC) when added to the PCR mixture. This point was not found under routine conditions when the IC was added during the extraction step. The second is a lack of practicality, as the mixture is distributed over several vials, requiring numerous pipetting operations. Overall, this study provides useful information for the molecular diagnosis of toxoplasmosis; the analytical and clinical performances of the Sacace PCR kit were satisfactory, the kit having sensitivity and specificity similar to those of expert center methods and being able to detect low parasite loads, at levels where multiplicative analysis gives inconsistently positive results. Finally, the study recommends multiplicative analysis in particular for amniotic fluids, aqueous humor, and other single specimens.

Congenital Toxoplasmosis and Long-term Outcomes

Objective: Congenital toxoplasmosis (CT) can have severe early and late sequelae in children. In this study, we aimed to evaluate the demographic, clinical, treatment characteristics of patients diagnosed with congenital Toxoplasma infection and to highlight the long-term complications of the patients. Methods: Patients with CT were included in this study who were followed between 2010 and 2022 in Cukurova University Medical Faculty Hospital. Demographic, clinical and treatment characteristics were searched retrospectively. In the diagnosis of maternal and CT, Toxoplasma IgM, IgG, IgG avidity, T. gondii polymerase chain reaction tests were used along with clinical and symptoms. Results: Eighteen children (two twins) with CT and their mothers (n=16) were included in the study. Median age was 1 month. Ten (55.5%) of the children were male. CT diagnosis was made during pregnancy in 7 mothers (resulting in 8 babies) and postnatally in 9 mothers (resulting in 10 babies). The mothers of 5 (31.1%) babies with CT received spiramycin treatment during pregnancy. Three (60%) of 5 pregnant women who received spiramycin were diagnosed in the first trimester, 4 (80%) of the babies did not have any sequale and only 1 (20%) had microphthalmia. Ocular involvement was the most common presentation of the disease occured in 10 patients (55.5%), hydrocephalus and intracranial calcification developed in five patients (27.7%). Hearing loss developed in 2 (11.1%) patients. During the follow-up period, seizures developed in 3 patients (16.6%), microcephaly in 2 patients (11.1%), and neurodevolopmental retardation in 7 patients (38.8%), two of the patients had severe mental retardation. One (5.5%) patient with hydrocephalus died at 36 months of age due to complications after ventriculoperitoneal shunt application. Conclusion: In our study, we observed severe sequelae in vision, hearing, and neurodevelopmental aspects in children diagnosed with CT at birth and during follow-ups. Early diagnosis and treatment of infants, along with the detection of Toxoplasma infection during pregnancy, are essential in preventing severe sequelae that may arise due to CT.

Comparative performance of ISAGA IgM and ELISA assays for the diagnosis of maternal and congenital Toxoplasma infections: which technique could replace ISAGA IgM?

The ISAGA immunocapture test for the detection of anti-Toxoplasma immunoglobulin M is a manual technique known for its excellent sensitivity and specificity. The purpose of this retrospective, multicenter study was to compare the performances and agreement between ISAGA and other IgM detection techniques before cessation of ISAGA production. The analytic performance of the different tests was evaluated using 1,341 serum samples from adults with positive IgM and negative IgG to Toxoplasma gondii, and 1,206 sera from neonates born to mothers with seroconversion. The agreement between the tests was evaluated on 13,506 adult and 5,795 child serum samples. The sensitivity of Toxo-ISAGA IgM® (adults 98.7%, neonates 63.1%) was similar to that of Platelia Toxo IgM® (adults 94.4%, neonates 64.6%), and significantly higher than Liaison Toxo IgM® (adults 90.6%), Architect/Alinity Toxo IgM® (adults 95.7%, neonates 48.6%), and Vidas Toxo IgM® (adults 81.8%, neonates 17.5%). However, the specificities varied between 24.4% (Platelia Toxo IgM®) and 95.2% (Liaison Toxo IgM®) in adults and were >95% for all tests in neonates. An analysis of the kappa coefficients showed better agreement between ISAGA IgM® and the other tests in children (0.75-0.83%) than in adults (0.11-0.53%). We conclude that, in the absence of Toxo-ISAGA IgM®, the association of a very sensitive technique (Platelia Toxo IgM® or Architect/Alinity Toxo IgM®) and a very specific technique (Vidas Toxo IgM® or Liaison Toxo IgM®) is recommended for IgM detection in adult sera. For neonates, Platelia Toxo IgM® appeared to be the best alternative to replace Toxo-ISAGA IgM®.

Title: Performances comparatives des tests ISAGA IgM et ELISA pour le diagnostic des infections maternelles et congénitales à Toxoplasma : quelle technique pourrait remplacer ISAGA IgM ? Abstract: Le test d'immunocapture ISAGA pour la détection des immunoglobulines M anti-Toxoplasma est une technique manuelle connue pour son excellente sensibilité et spécificité. Le but de cette étude rétrospective et multicentrique était de comparer les performances et la concordance entre l'ISAGA et d'autres techniques de détection d'IgM avant l'arrêt de la commercialisation de l'ISAGA. Les performances analytiques des différents tests ont été évaluées à partir de 1 341 échantillons de sérum d'adultes présentant des IgM positives et des IgG négatives à Toxoplasma gondii, et de 1 206 sérums de nouveau-nés nés de mères présentant une séroconversion. La concordance entre les tests a été évaluée sur 13 506 échantillons de sérum d'adultes et 5 795 sérums d'enfants. La sensibilité de Toxo-ISAGA IgM® (adultes 98,7 %, nouveau-nés 63,1 %) était similaire à celle de Platelia Toxo IgM® (adultes 94,4 %, nouveau-nés 64,6 %) et significativement supérieure à celle de Liaison Toxo IgM® (adultes 90,6 %), Architect/Alinity Toxo IgM® (adultes 95,7 %, nouveau-nés 48,6 %) et Vidas Toxo IgM® (adultes 81,8 %, nouveau-nés 17,5 %). Cependant, les spécificités variaient entre 24,4 % (Platelia Toxo IgM®) et 95,2 % (Liaison Toxo IgM®) chez les adultes et étaient >95 % pour tous les tests chez les nouveau-nés. L'analyse des coefficients kappa a montré une meilleure concordance entre ISAGA IgM® et les autres tests chez les enfants (0,75­0,83%) que chez les adultes (0,11­0,53%). Nous concluons qu'en l'absence de Toxo-ISAGA IgM®, l'association d'une technique très sensible (Platelia Toxo IgM® ou Architect/Alinity Toxo IgM®) et d'une technique très spécifique (Vidas Toxo IgM® ou Liaison Toxo IgM®) est recommandée pour la détection des IgM dans les sérums adultes. Pour les nouveau-nés, Platelia Toxo IgM® apparaît comme la meilleure alternative en remplacement de Toxo-ISAGA IgM®.

Could PLATELIA Toxo IgM be the new gold standard for the serological diagnosis of congenital toxoplasmosis: a French multicenter study.

To assess the performance of PLATELIA Toxo IgM (Bio-Rad) and Toxo ISAGA (BioMérieux) to detect anti-Toxoplasma IgM in infants at risk of congenital toxoplasmosis, a retrospective multicenter study was conducted comparing serological results obtained in the framework of routine diagnosis work-up for congenital toxoplasmosis. All infants born to mothers infected with T. gondii during pregnancy from 2010 to 2020 with at least 6 months of serological follow-up were included (n = 1,010). One thousand ten cases were included, of which 250 infants (24.75%) had congenital toxoplasmosis. A total of 1039 sera were included. The concordance between the two techniques was 96%, with kappa coefficient of 0.87, showing an almost perfect agreement between ISAGA and PLATELIA. Cumulative sensitivity and specificity were 73.2% and 99.5.% and 74.8% and 100% for ISAGA and PLATELIA, respectively. The mean time to detect IgM using ISAGA and PLATELIA tests was 6.9 ± 20.1 days and 5.6 ± 14.7 days, respectively not significant (ns). Finally, the sensitivity of ISAGA and PLATELIA to detect IgM antibodies in infected neonates at 5 days of life was 62% and 64%, respectively. Performances of PLATELIA Toxo IgM assay were comparable to the gold standard ISAGA. This enzyme-linked immunosorbent assay is suitable for routine serology for the diagnosis of congenital toxoplasmosis in newborns. IMPORTANCE This study will help clinical microbiologists to chose an alternative serological method for the neonatal diagnosis of congenital toxoplasmosis, once the gold standard technique ISAGA will be withdrawn next year.

Toxoplasma gondii infections in pediatric neurosurgery.

Toxoplasma gondii is a parasite that is estimated to infect one-third of the world's population. It is acquired by ingesting contaminated water and food specially undercooked meat, contact with domestic or wild feline feces, and during pregnancy by transplacental transmission.Immunocompetent hosts are usually asymptomatic, and infection will be self-limited, while those patients whose immune system is debilitated by HIV infection, immunosuppressive therapy, long-term steroid treatment, and fetuses infected during gestation will show evidence of systemic activity which is more severe in the central nervous system and eyes due to insufficient immune response caused by their respective blood barriers. Congenital toxoplasmosis has an estimated incidence of 8% in mothers who were seronegative at the beginning of their pregnancy. Infection in the first trimester may result in spontaneous abortion or stillbirth; however, it is estimated that the highest risk for vertical transmission is during the second and third trimesters when blood flow and placenta thickness favor parasitic transmission.Congenital toxoplasmosis can be detected with periodic surveillance in endemic areas, and with appropriate treatment, the risk of vertical transmission can be reduced, and the severity of the disease can be reversed in infected fetuses.While most infected newborns will show no evidence of the disease, those who suffer active intrauterine complications will present with cerebral calcifications in 8-12% of cases, hydrocephalus in 4-30%, and chorioretinitis in 12-15%. Also, seizure disorders, spasticity, and varying degrees of neurocognitive deficits can be found in 12%.Four distinct patterns of hydrocephalus have been described: aqueductal stenosis with lateral and third ventricle dilatation, periforaminal calcifications leading to foramen of Monro stenosis with associated asymmetrical ventricle dilatation, a mix of aqueductal and foramen of Monro stenosis, and overt hydrocephalus without clear evidence of obstruction with predominant dilatation of occipital horns (colpocephaly).While all patients diagnosed with congenital toxoplasmosis should undergo pharmacological treatment, those presenting with hydrocephalus have traditionally been managed with CSF shunting; however, there are reports of at least 50% success when selected cases are treated with endoscopic third ventriculostomy. Successful hydrocephalus management with appropriate treatment leads to better intellectual outcomes.

Real-time PCR in the diagnosis of congenital toxoplasmosis.

The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of newborns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid.

Contribution of serology in congenital toxoplasmosis diagnosis: results from a 10-year French retrospective study.

This study aimed to evaluate different serological strategies for the postnatal diagnosis of congenital toxoplasmosis (CT) and establish a biological algorithm for CT diagnosis. The study analyzed serological data of immunoglobulins M, A, and G (IgM, IgA, IgG) performed by immunoenzymatic and compared immunological profile (CIP) assays in 668 newborns with CT diagnosis across four testing periods: P1 (D0- D10), P2 (D11-D35), P3 (D36-D45), and P4 (>D45). Forty-nine percent of the 668 CT cases were diagnosed during P1 and 34%, 4%, and 12% during P2, P3, and P4, respectively. CIP assays detected neosynthetized IgMs/IgGs in 98% of CT cases diagnosed during P1, while IgMs and IgAs were detected in 90% and 57% of CT cases diagnosed during P2 and in 88% and 67% of diagnoses made during P3, respectively. Detection of neosynthesized IgMs/IgGs, IgMs, and IgAs by immunoassay contributed to CT diagnosis in 81%, 77%, and 60% of cases, respectively. In total, 46% of serum samples were positive for all three parameters, 27% for two, and 27% for one of the three. The study recommends using the CIP assay as standard during P1 for CT diagnosis and IgM and IgA immunoassays after P1. A clinical and biological follow-up in a specialized center with a close collaboration between biologists and clinicians is highly recommended to increase the chances of early diagnosis. Overall, this study provides useful information for the development of a biological algorithm for CT diagnosis, which can aid in early detection and appropriate treatment of this disease.

Unspecific congenital toxoplasmosis in a two-month-old baby.

A two-month-old baby boy diagnosed with unspecific congenital toxoplasmosis was referred by a pediatrician to the Clinical Parasitology referral center at the Faculty of Medicine, Universitas Indonesia. Baby was post-hospitalized in the NICU and required ventilation support for one month. Furthermore, there was history of from various medical conditions, such as intracranial bleeding, convulsion, hypertrophic cardiomyopathy, retinopathy, and renal failure. After two month, there was no significant weight gain, anti-Toxoplasma IgM showed positive results, and anti-Toxoplasma IgM and IgG of the mother were also positive. Baby and mother were successfully treated with pyrimethamine, cotrimoxazole, and folinic acid for one month. At 2 years, there signs of normal motoric, eye, and hearing development with underdeveloped kidneys. Therefore, pre-pregnancy counseling and education aimed at preventing toxoplasmosis during pregnancy should be increased and conducted routinely by health workers or trained cadres to reduce the risk of fetal defects.

IgM triplet in neonatal diagnosis by immunoblotting and its potential use as a diagnostic marker for congenital toxoplasmosis.

Primary infection during pregnancy by the protozoan Toxoplasma gondii can be worrisome because transmission to the fetus may lead to congenital toxoplasmosis (CT). Neonatal diagnosis is usually performed by serological profile comparison of the mother and newborn. As previously reported in 2012 by C. L'Ollivier et al., three IgM bands at 75, 90 and 100 kDa called the "IgM triplet" has caught our attention and seems to be pathognomonic of CT. This retrospective multicenter study involved nine reference laboratories included in the French National Reference Center for Toxoplasmosis network and concerned determining the specificity and sensitivity of this IgM triplet. On this basis, we were able to propose a new read of the comparison of IgG and IgM immunoblot profiles of mother and infant to increase the sensitivity of this diagnostic marker. The effect of the trimester of pregnancy at the time of infection, but also of maternal treatment with pyrimethamine/sulfadiazine/folinic acid on the presence of this IgM triplet in the infant, could be studied. The presence of the triplet appears pathognomonic for the diagnosis of CT, and it increased the sensitivity of the immunoblot assay from 55.04% to 72.48%. As a result, it would be wise to enhance conventional immunoblot reading by adding the presence of the three IgM bands in the infant pattern for neonatal diagnosis of CT.

Title: La triplette IgM dans le diagnostic néonatal par immunoblot et son utilisation potentielle comme marqueur diagnostique de la toxoplasmose congénitale. Abstract: La primo-infection pendant la grossesse par le protozoaire Toxoplasma gondii peut se révéler préoccupante car la transmission au fœtus peut conduire à une toxoplasmose congénitale (TC). Un diagnostic néonatal est généralement réalisé par comparaison des profils sérologiques de la mère et du nouveau-né. Comme précédemment rapporté en 2012 par C. L'Ollivier et al., l'association de trois bandes d'IgM à 75, 90, et 100 kDa appelée la « triplette IgM ¼ a retenu notre attention et semble être pathognomonique de la TC. Cette étude rétrospective multicentrique impliquant neuf laboratoires de référence inclus dans le réseau du Centre National de Référence pour la Toxoplasmose a permis de déterminer la spécificité et la sensibilité de cette triplette IgM. Ainsi, cela a permis de proposer une nouvelle lecture de la comparaison des profils d'immunoblot IgG et IgM de la mère et du nourrisson pour augmenter la sensibilité de ce marqueur diagnostique. L'effet du trimestre de la grossesse au moment de l'infection mais aussi du traitement maternel par pyriméthamine/sulfadiazine/acide folinique sur la présence de la triplette IgM chez l'enfant a pu être analysé. La présence de cette triplette semble pathognomonique pour le diagnostic de TC et elle permet d'augmenter la sensibilité du test immunoblot de 55,04 % à 72,48 %. Ainsi, il pourrait être judicieux d'améliorer la lecture conventionnelle de l'immunoblot en ajoutant la présence des trois bandes IgM dans le schéma du nourrisson pour le diagnostic néonatal de TC.

Congenital Toxoplasmosis Diagnosis: Current Approaches and New Insights.

PURPOSE: The aim of this study is to describe and discuss current disadvantages in congenital toxoplasmosis (CT) diagnosis, and what can be improved or changed through new perspectives and technological advances. METHODS: We used Pubmed, Cochrane, and EBSCO databases to research publications from 10 years to date describing current diagnostic methods for CT. The keywords used for this Mini-Review were Toxoplasma gondii, congenital toxoplasmosis, diagnosis, and prospects using Boolean operators such as AND, OR, identifying scientific publications highlighting the importance of implementing new diagnostic methods. RESULTS: Current diagnosis methods have several disadvantages, i.e., time-consuming, low sensitivity or specificity, and non-cost effective, that bring up the necessity of improving or developing new approaches. Recombinant proteins can help improve specificity by generating tests that use circulating strains in a specific geographical region, SAG1 and BAG1, as they are expressed during a particular stage of the disease (acute or chronic, respectively), for its use in serological diagnoses, such as capture ELISA and immunochromatography. Point of Care (POC) tests are methods performed at the patient care site, which leads to rapid patient treatment; despite the advantages, several improvements and perspectives are necessary to be implemented globally. CONCLUSIONS: Although already established diagnosis methods for CT may be sufficient in some regions, there is still a persistent demand to develop tests with higher throughput, cost, and time reduction in developing countries, where prevalence is high. New approaches in CT diagnosis, such as recombinant proteins, capture ELISA, immunochromatography, and POC tests methods, can increase performance in terms of specificity and sensitivity simplifying diagnostic tests' requirements.

Maternal anti-Toxoplasma gondii antibodies IgG2, IgG3 and IgG1 are markers of vertical transmission and clinical evolution of toxoplasmosis in the offspring.

Toxoplasma gondii can be transmitted vertically during pregnancy and may cause neurological, ocular, and even systemic damage to the offspring. Congenital toxoplasmosis (CT) can be diagnosed during gestation and/or after birth in the postnatal period. The timely diagnosis is highly relevant for efficient clinical management. The most common laboratory methods for diagnosing CT are based on Toxoplasma-specific humoral immune responses. However, these methods are of low sensitivity or specificity. In a previous study with a small number of cases, the comparison of anti-T. gondii IgG subclasses between mothers and their offspring showed promising results for CT diagnosis and prognosis. Thus, in this work, we analyzed specific IgG subclasses and IgA in 40 T. gondii-infected mothers and their children, of which 27 were congenitally infected and 13 uninfected. A higher frequency of anti-Toxoplasma IgG2, IgG3, IgG4, and IgA antibodies was observed in mothers and congenitally infected offspring. Of these, IgG2 or IgG3 were statistically the most conspicuous. In the CT group, maternal IgG3 antibodies were significantly associated with severe disease of the infants and IgG1 and IgG3 with disseminated disease. The results support that maternal anti-T. gondii IgG3, IgG2 and IgG1 are markers of congenital transmission and severity/spread of disease in the offspring.

First description of congenital toxoplasmosis after maternal coinfection with Toxoplasma gondii and severe acute respiratory syndrome coronavirus 2: a case report.

BACKGROUND: Congenital toxoplasmosis can be associated with serious clinical consequences from fetus to adulthood. Hence, early detection is required to minimize severe sequelae through appropriate therapy. We describe the first case of a congenital toxoplasmosis after maternal coinfection with Toxoplasma gondii and severe acute respiratory syndrome coronavirus 2 and the challenging serological diagnosis of the disease in this context. CASE PRESENTATION: A Caucasian boy was born at 27 weeks 2 days of gestation by cesarean section due to maternal COVID-19-related respiratory failure. Postpartum serological screening of the mother revealed a previously unrecognized active Toxoplasma gondii infection. The premature child initially tested negative for anti- Toxoplasma gondii immunoglobulin A and M antibodies 1, 2 and 4 weeks after birth, whereas immunoglobulin G antibodies were only weakly positive with no evidence of child-specific production. Neither neurological nor ophthalmological abnormalities were detected. Approximately 3 months after birth, serological testing indicated a congenital toxoplasmosis by presence of immunoglobulin A and M, in combination with a child-specific immunoglobulin G synthesis. Additionally, cerebrospinal fluid was tested positive for Toxoplasma gondii DNA. Although no clinical manifestations of congenital toxoplasmosis were detected, an antiparasitic therapy was initiated to minimize the risk of late sequelae. There were no hints for a transplacental transmission of severe acute respiratory syndrome coronavirus 2. CONCLUSION: This case raises the awareness of possible coinfections with the risk of transplacental transmission in cases of maternal coronavirus disease 2019. The report emphasizes the need for screening vulnerable patients for toxoplasmosis in general and especially in the context of pregnancy. It becomes evident that prematurity can complicate the serological diagnosis of congenital toxoplasmosis due to a delayed antibody response. Repeated testing is recommended to carefully monitor children at risk and especially those with a history of preterm birth.

Congenital toxoplasmosis with severe neurological disease in a referral hospital in Peru. / Toxoplasmosis congénita con enfermedad neurológica severa en un hospital de referencia del Perú.

The aim of this study was to describe the epidemiological, clinical, and therapeutic characteristics of patients diagnosed with congenital toxoplasmosis (CT) with severe neurological disease. We reviewed the medical records of patients under 1 year of age with positive IgM test for Toxoplasma gondii and brain, eye, and/or hearing involvement. This study was carried out at the Instituto Nacional de Salud del Niño San Borja (INSNSB), Lima, Peru. Twenty-one patients diagnosed with CT were evaluated; 57.1% were female, and the median age at diagnosis was 3.1 months (IQR: 1.7-7.3). The main central nervous system manifestations were hydrocephalus (76.2%), intracranial calcifications (52.4%), microcephaly (42.9%), and convulsions (25.6%); the most frequent ocular manifestation was chorioretinitis (38.1%). In conclusion, 64% of CT cases had one or more manifestations of severe neurological disease.

El propósito del presente estudio fue describir las características epidemiológicas, clínicas, y terapéuticas de pacientes con diagnóstico de toxoplasmosis congénita (TC) con enfermedad neurológica severa. Se revisaron las historias clínicas de los pacientes menores de 1 año con serología IgM positiva para Toxoplasma gondii y compromiso encefálico, ocular y/o auditivo. El estudio se realizó en el Instituto Nacional de Salud del Niño San Borja (INSN-SB) en Lima, Perú. Se evaluaron a 21 pacientes con diagnóstico de TC, el 57,1% fueron del sexo femenino y la mediana de edad al momento del diagnóstico fue 3,1 meses (RIC: 1,7-7,3). Las principales manifestaciones del sistema nervioso central fueron hidrocefalia (76,2%), calcificaciones intracraneales (52,4%), microcefalia (42,9%), y convulsiones (25,6%); la manifestación ocular más frecuente fue la coriorretinitis (38,1%). En conclusión, 64% de los casos de TC tuvieron una o más manifestaciones de enfermedad neurológica severa.

Transmisión vertical de Toxoplasma gondii asociado a la edad gestacional / Vertical transmission of Toxoplasma gondii associated with gestational age

Una de las principales consecuencias de la infección por Toxoplasma gondii en mujeres embarazadas es la transmisión vertical al feto. Aunque es poco frecuente, la toxoplasmosis congénita puede causar enfermedades neurológicas u oculares graves. La infección primaria por T. gondii durante el embarazo puede tener consecuencias peligrosas, como retinocoroiditis, hidrocefalia, calcificaciones cerebrales, encefalitis, esplenomegalia, pérdida de audición, ceguera y muerte. La atención prenatal debe incluir educación sobre la prevención de la toxoplasmosis. Se trata de un estudio observacional, analítico y transversal. Se evaluaron 209 mujeres gestantes e igual número de recién nacidos; 136 de las mujeres embarazadas resultaron con infección aguda positiva a IgM. De estas 51,20% y 64,71% resultaron primoinfectadas según la determinación de IgA e IgG avidez, respectivamente. 20 de los 35 neonatos provenientes de madres primoinfectadas, adquirieron la infección congénita en el tercer trimestre de la gestación. La conciencia sobre la prevención y el control de la toxoplasmosis es baja entre las poblaciones de alto riesgo. Es necesario fortalecer la educación en salud relacionada con la prevención y el control de la toxoplasmosis en las mujeres en edad reproductiva para prevenir la transmisión vertical a sus productos de gestación y evitar los efectos negativos y hasta mortales de la inefcción por el parásito(AU)

One of the main consequences of Toxoplasma gondii infection in pregnant women is vertical transmission to the fetus. Although rare, congenital toxoplasmosis can cause serious neurological or ocular disease. Primary T. gondii infection during pregnancy can have dangerous consequences, including retinochoroiditis, hydrocephalus, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Prenatal care should include education on the prevention of toxoplasmosis. This is an observational, analytical and cross-sectional study. 209 pregnant women and the same number of newborns were evaluated; 136 of the pregnant women were acutely infected with IgM. Of these, 51.20% and 64.71% were primary infected according to the determination of IgA and IgG avidity, respectively. 20 of the 35 neonates from mothers with primary infection acquired the congenital infection in the third trimester of pregnancy. Awareness of toxoplasmosis prevention and control is low among high-risk populations. It is necessary to strengthen health education related to the prevention and control of toxoplasmosis in women of reproductive age to prevent vertical transmission to their gestational products and avoid the negative and even fatal effects of infection by the parasite(AU)

Prevention of congenital toxoplasmosis in France using prenatal screening: A decision-analytic economic model.

BACKGROUND: Toxoplasma 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. OBJECTIVE: To evaluate the ability of the French prenatal retesting program to reduce the lifetime costs of congenital toxoplasmosis. METHODS: We 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. FINDINGS: Total 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. INTERPRETATION: Screening 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.

Diagnostic accuracy of adjusted low IgG avidity index to predict acute Toxoplasma gondii infection in the first trimester of pregnancy.

Congenital toxoplasmosis is reportable disease in Europe. To prevent it antibody serological tests were introduced in several European countries as a part of screening programmes. Immunoglobulin G (IgG) avidity index testing is one of these tests for diagnosing acute infection with Toxoplasma gondii (Nicolle et Manceaux, 1908) in pregnant women. However, a low or moderate IgG avidity index can give inconclusive results for predicting woman's status. From June 2012 until the end of 2014, 17,990 women were included in the national screening program to prevent congenital toxoplasmosis. One hundred and twenty-six women were consecutively included in the study because they had low or moderate IgG avidity. Every woman with possible acute toxoplasmosis was followed up every month till delivery. Fifty-eight of 126 (46%) women got infected in months before current pregnancy, 39 women (31%) were infected early in pregnancy. Twenty-nine pregnant women of 126 (23%) got infected in the second/third trimester of pregnancy. New cut off for IgG avidity index was 0.11. With this cut off, we were able to exclude T. gondii acute infection in the first trimester with very good diagnostic accuracy (area under the curve (AUC) = 0.95, 95% confidence Interval (CI) 0.91-0.99, sensitivity 0.95, specificity 0.86). If an IgG avidity index above 0.11 is measured in a woman's serum and she is in the first trimester of pregnancy, then a odds ratio (OR) for acute infection with T. gondii is below 1 (OR 0.11, 95% CI 0.05-0.25, P < 0.0001). If we measure IgG avidity index that is ≥ 0.11 in the first trimester of pregnancy, we can exclude infection with T. gondii with good diagnostic accuracy in our cohort of women. With a new cut off we could reduce number of invasive procedures such as amniocentesis and put less pregnant women in distress.

[Ocular toxoplasmosis in infants 0 to 12 months of age with congenital toxoplasmosis]. / Toxoplasmosis ocular en lactantes de 0 a 12 meses de edad con toxoplasmosis congénita.

BACKGROUND: Ocular toxoplasmosis (OT) is a retinochoroiditis that evolves with several episodes of inflammation and can occur both in the congenital or acquired form of the disease, Aim: To describe the frequency and clinical characteristics of OT in infants aged 0 to 12 months, children of mothers with positive serology for toxoplasmosis in the perinatal period. METHODS: Cross-sectional descriptive, ambispective study. RESULTS: Infants from 0 to 12 months of age, whose mothers had positive serology for toxoplasmosis in the perinatal period, referred to the pediatric ophthalmology service for evaluation, were admitted. Demographic variables, maternal and infant serology and the results of the ophthalmological examination were collected. Data were analyzed in SPSS v21 Results: 46.4% of 125 infants had OT, of them 67.2% were female, (p = 0.04) the median age was 6 months, 41% had IgG and IgM positive. The lesions were bilateral in 82.8%, central in 86.2%, and inactive in 81%. Retinochoroiditis was accompanied by strabismus in 41%. CONCLUSIONS: The frequency of OT in this population of infants with congenital toxoplasmosis was high. more than 80% of the eye lesions were inactive, centrally located and bilaterally involved.