Ultrasound features of fetal toxoplasmosis: A contemporary multicenter survey in 88 fetuses.

OBJECTIVE: To describe the lesions detected by prenatal ultrasound examination in congenital toxoplasmosis (CT). METHODS: We retrospectively analyzed all cases of fetal infection with Toxoplasma gondii with ultrasound anomalies described by fetal medicine experts in 2009 to 2019 in 30 French centers. RESULTS: Eighty-eight cases of CT were included. Forty-five (51.1%) had one or more cerebral signs only, 35 (39.8%) had cerebral plus extracerebral signs and 8 (9.1%) had extracerebral signs only. The main cerebral signs were intracranial hyperechogenic nodular foci (n = 60) of which 20 were isolated, ventriculomegalies (n = 44) which generally increased during follow-up, and periventricular abscesses (n = 12). The main extracerebral signs were hepatomegaly and/or splenomegaly (n = 14), small for gestational age (n = 14), ascites (n = 14, including 2 with hydrops), and hyperechogenic bowel (n = 11). Maternal infection occurred mostly in the first or second trimester (81 cases), periconceptionally in one and in the third trimester in six cases. The first ultrasound signs were detected after a median of 7 weeks (range: 1.4; 24.0) following maternal toxoplasmosis seroconversion. CONCLUSION: While no sign was specific of CT, there were typical associations of cerebral signs with or without extracerebral signs. Detailed ultrasound examination could improve prognostic evaluation, as well as diagnosis of CT in settings lacking serological screening.

Visual Outcomes in Presumed Congenital Foveal Toxoplasmosis.

PURPOSE: Congenital macular lesions attributed to toxoplasmosis may limit potential visual acuity. The appearance and location of these scars may cause physicians to overlook associated amblyopia. This study reviews the visual outcomes and benefits of amblyopia therapy in children with foveal toxoplasmosis scars. DESIGN: Retrospective observational case series. METHODS: Setting: Single center. PATIENT POPULATION: Children with presumed foveal toxoplasmosis scars who underwent amblyopia treatment. MAIN OUTCOME MEASURE: Charts were reviewed for amblyopia treatment, fundus photographs, optical coherence tomography (OCT), and visual acuity. RESULTS: Median age at presentation was 2.8 years and median follow-up was 6.2 years. Occlusion therapy was undertaken in 9 patients. Median duration of occlusion therapy was 1.7 years. Six patients improved with occlusion therapy (average 4.6 lines gained on optotype acuity). Final visual acuity ranged from 20/25 to 20/250, with 6 of 8 patients better than 20/80. OCT confirmed macular scars in 5 patients, with varying degrees of foveal architecture disruption. CONCLUSION: Despite the striking appearance of the lesions in patients with presumed foveal toxoplasmosis, visual potential may be better than expected. The appearance of the lesions is not always predictive of visual outcome. A trial of occlusion therapy to treat amblyopia should be initiated in these patients to ensure that they reach their maximal visual potential.

Congenital Toxoplasmosis Presenting as Eosinophilic Encephalomyelitis With Spinal Cord Hemorrhage.

A 4-week-old male neonate with a history of intermittent hypothermia in the newborn nursery presented with an acute onset of bilateral lower extremity paralysis and areflexia. Extensive workup demonstrated eosinophilic encephalomyelitis and multifocal hemorrhages of the brain and spinal cord. Funduscopic examination revealed bilateral chorioretinitis with macular scarring. The laboratory values were notable for peripheral eosinophilia and cerebrospinal fluid eosinophilic pleocytosis (28 white blood cells/µL, 28% eosinophils), markedly elevated protein (1214 mg/dL), and hypoglycorrhachia (20 mg/dL). Toxoplasma gondii immunoglobulin M (IgM) test result was positive. Reference testing obtained at the Palo Alto Medical Foundation Toxoplasma Serology Laboratory confirmed the diagnosis of congenital toxoplasmosis in the infant with a positive immunoglobulin G (IgG) dye test result, immunoglobulin A enzyme-linked immunosorbent assay, and IgM immunosorbent agglutination assay. The diagnosis of an infection acquired during gestation in the mother was established by a positive maternal IgG dye test result, IgM enzyme-linked immunosorbent assay, immunoglobulin A, immunoglobulin E, and low IgG avidity. At 6-month follow-up, the infant had marginal improvement in his retinal lesions and residual paraplegia with hyperreflexia and clonus of the lower extremities. A repeat MRI demonstrated interval development of encephalomalacia with suspected cortical laminar necrosis and spinal cord atrophy in the areas of previous hemorrhage. Clinicians should be aware of this severe spectrum of congenital toxoplasmosis disease and should remain vigilant for subtler signs that may prompt earlier testing, diagnosis, and treatment.

Sonographic Detection of Seizure-Like Activity in Fetuses with Congenital Infection: Report of Three Cases and Review of the Literature.

Fetal seizure is a very rare prenatal finding and associated with an almost invariably poor outcome, the most common causes being hypoxic-ischemic encephalopathy, congenital anomalies of either the central nervous system (CNS) or musculoskeletal system, and metabolic disorders. The prenatal detection of seizure-like activity in fetuses with congenital infection has not been previously reported. In this report, we describe 3 cases of seizures in fetuses with congenital infection including Zika virus (n = 2) and toxoplasmosis (n = 1). All 3 fetuses had associated CNS abnormalities and the perinatal outcome was uniformly poor. This report suggests that for fetuses with proven congenital infections an extended and targeted sonographic examination may be helpful in -detecting associated fetal seizures that may even worsen the neonatal outcome.

Neuroimaging Findings of Congenital Toxoplasmosis, Cytomegalovirus, and Zika Virus Infections: A Comparison of Three Cases.

OBJECTIVE: Toxoplasmosis, cytomegalovirus (CMV), and Zika virus (ZIKV) are among the common infectious agents that may infect the fetuses vertically. Clinical presentations of these congenital infections overlap significantly, and it is usually impossible to determine the causative agent clinically. The objective was the comparison of neuroimaging findings in three fetuses who underwent intrauterine infection by toxoplasmosis, CMV, and ZIKV. METHODS: Three confirmed cases of congenital toxoplasmosis, CMV, and ZIKV infections were included in the study over 7 months prospectively. Prenatal ultrasound, fetal brain MRI, and postnatal neuroimaging (CT or MRI) were performed on all of the included cases and interpreted by an expert radiologist. RESULTS: The mean GA at the time of prenatal imaging was 34.5 ± 3.5 weeks. The main neuroimaging findings in congenital toxoplasmosis were randomly distributed brain calcifications and ventricular dilatation on ultrasounds (US), as well as white matter signal change on fetal brain MRI. The main neuroimaging findings of congenital CMV infection included microcephaly, ventriculomegaly, and periventricular calcifications on US, as well as pachygyria revealed by fetal MRI. The case of congenital ZIKV infection showed microcephaly, ventriculomegaly, and periventricular calcifications on ultrasound, as well as brain atrophy and brain surface smoothness on fetal MRI. CONCLUSION: Although the neuroimaging findings in congenital infections are not pathognomonic, in combination with the patient history may be suggestive of one of the infectious agents, which will guide the management strategy.

Report of an unsual case of anophthalmia and craniofacial cleft in a newborn with Toxoplasma gondii congenital infection.

BACKGROUND: We present one unusual case of anophthalmia and craniofacial cleft, probably due to congenital toxoplasmosis only. CASE PRESENTATION: A two-month-old male had a twin in utero who disappeared between the 7th and the 14th week of gestation. At birth, the baby presented anophthalmia and craniofacial cleft, and no sign compatible with genetic or exposition/deficiency problems, like the Wolf-Hirschhorn syndrome or maternal vitamin A deficiency. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neo-antibodies in western blot, as well as by real time PCR in blood. CMV infection was also discarded by PCR and IgM negative results. Structures suggestive of T. gondii pseudocysts were observed in a biopsy taken during the first functional/esthetic surgery. CONCLUSIONS: We conclude that this is a rare case of anophthalmia combined with craniofacial cleft due to congenital toxoplasmosis, that must be considered by physicians. This has not been reported before.

Genotyping of Toxoplasma gondii strain directly from human CSF samples of congenital toxoplasmosis clinical case.

This report describes a case of congenital toxoplasmosis in a newborn in Southern Italy. A pregnant mother had been admitted at the 20th week of her pregnancy on account of pharyngodynia and laterocervical lymphadenopathy. Although serological testing of the mother's serum documented a seroconversion with positive IgG and IgM anti-Toxoplasma antibodies during II trimester, the woman refused to perform prenatal diagnosis for congenital toxoplasmosis. Fetal ultrasound scan already showed mild asymmetrical triventricular hydrocephaly and cerebral calcifications. After birth, real-time PCR on cerebrospinal fluid and blood samples of the newborn showed a positive result for 529bp-repeat element DNA of T. gondii, In addition brain magnetic resonance imaging and computed tomography showed a characteristic diffuse brain tissue loss associated with hydrocephalus. For the first time molecular characterization of T. gondii isolate was performed directly from the newborn's CSF samples by using nested-PCR-RFLP of sag-2 and pk1 genes. The PCR-RLFP analysis revealed that the isolate belongs to the clonal type II, the predominant lineage causing human toxoplasmosis, as confirmed by DNA sequencing.

Prognosis of Fetal Parenchymal Cerebral Lesions without Ventriculomegaly in Congenital Toxoplasmosis Infection.

OBJECTIVE: To evaluate the neurodevelopmental and ocular outcome of a continuous retrospective series of fetal toxoplasmosis infections for which prenatal ultrasound (US) follow-up revealed abnormal cerebral findings without associated ventriculomegaly. MATERIALS AND METHODS: We retrospectively reviewed all cases of proven fetal Toxoplasma gondii infection with fetal cerebral anomalies at US examination without significant ventriculomegaly (≥10 mm) evaluated in our center over a 5-year period. US and magnetic resonance imaging findings were collected. The neurodevelopmental and ocular outcomes of the cases were studied. RESULTS: Nine fetuses were included. Hyperechogenic foci of the cerebral parenchyma were isolated in five cases. Among those, four children had normal neurological development. Amblyopia was detected in on case. Hyperechogenic foci were associated with other anomalies of cerebral parenchyma in three cases among which two children had normal neurological development. Termination of pregnancy was performed in three cases: one case within the context of severe maternal schizophrenia with isolated hyperechogenic foci, one case where hyperechogenic foci were associated with extensive lesions of the white matter, and one case for severe fetal hydrops. CONCLUSION: The neurological prognosis of cerebral hyperechogenic lesions without ventriculomegaly in fetal toxoplasmosis infection may be favorable. The risk of ocular damage however remains high and unpredictable in the prenatal period.

Congenital toxoplasmosis presenting as central diabetes insipidus in an infant: a case report.

BACKGROUND: Congenital toxoplasmosis has a wide range of presentation at birth varying from severe neurological features such as hydrocephalus and chorioretinitis to a well appearing baby, who may develop complications late in infancy. While neuroendocrine abnormalities associated with congenital toxoplasmosis are uncommon, isolated central diabetes insipidus is extremely rare. CASE PRESENTATION: Here, we report on a female infant who presented with fever, convulsions, and polyuria. Examination revealed weight and length below the 3rd centile along with signs of severe dehydration. Fundal examination showed bilateral chorioretinitis. This infant developed hypernatremia together with increased serum osmolality and decreased both urine osmolality and specific gravity consistent with central diabetes insipidus. Serology for toxoplasma specific immunoglobulin M was high for both the mother and the baby and polymerase chain reaction for toxoplasma deoxyribonucleic acid was positive in the infant confirming congenital toxoplasmosis. Brain computerized tomography scans demonstrated ventriculomegaly associated with cerebral and cortical calcifications. Fluid and electrolyte abnormalities responded to nasal vasopressin therapy. CONCLUSION: This report highlights central diabetes inspidus as a rare presentation of congenital toxoplasmosis.

Functional echocardiography in the fetus with non-cardiac disease.

We describe the hemodynamic changes observed in fetuses with extra cardiac conditions such as intrauterine growth restriction, tumors, twin-twin transfusion syndrome, congenital infections, and in fetuses of mothers with diabetes. In most fetuses with mild extra cardiac disease, the alterations in fetal cardiac function remain subclinical. Cardiac function assessment has however helped us to achieve a better understanding of the pathophysiology of these diseases. In fetuses at the more severe end of the disease spectrum, functional echocardiography may help in guiding clinical decision-making regarding the need for either delivery or fetal therapy. The growth-restricted fetus represents a special indication for routine cardiac function assessment, as in utero hemodynamic changes may help optimize the timing of delivery. Moreover, in intrauterine growth restriction, the altered hemodynamics causes cardiovascular remodeling, which can result in an increased risk of postnatal cardiovascular disease.

Comparison of prevalence of toxoplasma and cytomegalovirus infection in cases with fetal ultrasound markers in the second trimester of pregnancy.

OBJECTIVES: To evaluate the prevalence of toxoplasma and cytomegalovirus (CMV) infections in cases of ultrasound anomalies detected in the second trimester of pregnancy. METHODS: Serological examinations for toxoplasma and CMV infection were carried out in 655 cases with sonographic findings suggestive of fetal infection, 612 cases with single ultrasound markers and 43 cases with two or more markers. RESULTS: In cases of single ultrasound markers, serological examination diagnosed recent toxoplasma infection in 107/612 cases (17.5%) and recent CMV infection in 75 cases (12.3%). Recent toxoplasma infection accounted for 13.8% (52/377) of the intracranial sonographic findings and 23.9% (45/188) of the abdominal findings, whereas recent CMV infections accounted for 12.2 (46/377) and 11.7% (22/188), respectively. Recent CMV infection with sonographic manifestations had higher rates of intracranial than intra-abdominal sonographic findings (46/75 or 61% vs 22/75 or 29%), whereas recent toxoplasma infection with sonographic manifestations had similar rates of intracranial (52/107 or 49%) and intra-abdominal (45/107 or 42%) findings. In cases of two or more ultrasound markers, serological examination diagnosed recent toxoplasma infection in 12/43 cases (27.9%) and recent CMV infection in 10/43 cases (23.3%). CONCLUSIONS: Ultrasound findings suspicious for toxoplasma and CMV infection are not pathognomonic for either pathologic entity.

Agreement between ultrasonography and computed tomography in detecting intracranial calcifications in congenital toxoplasmosis.

AIM: To evaluate the agreement between ultrasound (US) and computed tomography (CT) in detecting intracranial calcification in infants with congenital toxoplasmosis. MATERIALS AND METHODS: Forty-four infants referred for investigation of congenital toxoplasmosis were prospectively evaluated, and the diagnosis was confirmed or ruled out by serological testing and by follow-up in the first year of life. The investigation protocol included cranial US and cranial CT, and examinations were conducted and interpreted by two radiologists blinded to the results of the other imaging test and to the diagnostic confirmation. RESULTS: The diagnosis of congenital toxoplasmosis was confirmed in 33 patients, and agreement between US and CT findings was found in 31 of these cases. Both methods detected calcifications in 18 patients, and neither detected calcifications in 13 patients. Overall agreement was 94% and the kappa coefficient was 0.88 (95% confidence interval: 0.71, 1; p<0.001), which revealed almost perfect agreement between the two diagnostic methods. CONCLUSION: In this study, US and CT demonstrated equal sensitivity in the detection of intracranial calcification in infants with congenital toxoplasmosis.

[Contribution of the real time PCR in antenatal diagnosis of congenital toxoplasmosis]. / Apport de la pcr en temps réel dans le diagnostic anténatal de la toxoplasmose congénitale.

BACKGROUND: The antenatal diagnosis of congenital toxoplasmosis rests in Tunisia on ultrasonography coupled with biological explorations. Among these explorations the search of Toxoplasma gondii by means of real time PCR in amniotic fluid is the examination of choice. AIM: We report the results of 33 parturients for which the biological examinations allowed to retain the notion of perigravidic or pergravidic toxoplasmic infection. METHODS: They were 13 patients having a seroconversion during the pregnancy, 19 having anti-toxoplasmic IgM with a low or intermediate index of avidity and a patient having presented a symptomatic anteconceptional primary infection. The ADN was extracted by means of the Kit (Qiagen). Genic amplification by PCR TaqMan targeted a portion of 71 pairs of bases of the B 1 gene. RESULTS: The PCR was positive among 9 patients (27.3%). They were a patient having presented a symptomatic toxoplasmosis during the pregnancy, 4 patients having consulted only in the 2nd quarter and for which the index of avidity was intermediate and 4 patients having presented seoconversions of 1st (n=1) of 2nd (n=2) or 3rd trimester. Among these patients, 2 had a medical interruption of pregnancy. The 7 others were put under pyrimethamine sulfadiazine. The neonatal assessment practised at 5 new-born babies was negative in all the cases. The PCR was negative for 24 patients. 18 pregnancies were followed. The neonatal serology was negative. The follow-up of 13 newborn child showed the disappearance of the antitoxoplasmic IgG between the 6th and 12th month.

Outcome for children infected with congenital toxoplasmosis in the first trimester and with normal ultrasound findings: a study of 36 cases.

OBJECTIVE: We wished to investigate the prognosis of children infected with Toxoplasma gondii during the first trimester of pregnancy and whose ultrasound findings were entirely normal, in order to find out whether congenital toxoplasmosis did or did not justify termination of pregnancy if there was no fetal abnormality on ultrasound. STUDY DESIGN: A prospective and retrospective study was carried out by 12 French centers who enrolled 36 children infected with T. gondii during the first trimester of pregnancy and whose ultrasound examinations showed no anomaly. The outcome of these children after the age of 12 months (mean 50 months, range 12-144 months) was analyzed. RESULTS: Of the 36 infected children, 28 (78%) presented subclinical toxoplasmosis. Only specific IgG antibodies persisted after 1 year. The principal manifestation in 7 children (19%) was chorioretinitis without major vision loss. Their intellectual development was entirely normal. One child (3%) developed severe congenital toxoplasmosis. CONCLUSION: Since 97% of children infected with toxoplasmosis during the first trimester of pregnancy are asymptomatic or only slightly affected, we believe that in such circumstances termination of pregnancy is not indicated. However, appropriate treatment is essential and prenatal ultrasound examinations should be free of any anomaly.

Too late prenatal diagnosis of fetal toxoplasmosis: a case report.

OBJECTIVE: We describe a case of severe fetal hydrocephalus due to toxoplasmosis which could not be diagnosed until late gestational age due to the lack of a serologic surveillance program during pregnancy; moreover, this case points to the usefulness of molecular biology tools in the diagnostic process. Abnormal ultrasound in the 2nd trimester was noticed and Toxoplasma gondii was demonstrated in amniotic fluid at the 28th week of gestation both by PCR and by mice inoculation. Fansidar and folinic acid were administered. The newborn suffered from progressive hydrocephalus, seizures, and pathological muscular tonus; ultrasound examination showed massive cerebral calcifications. Ophthalmologic examination revealed bilateral choroidoretinitis. Congenital toxoplasmosis was confirmed by the detection of anti- T. gondii IgM and IgA in the neonatal serum. CONCLUSION: The presented case is an example of severe fetal toxoplasmosis diagnosed and treated in utero.

Prenatal study of fetal endocardial hyperrefringence and its relation to maternal toxoplasmosis.

OBJECTIVE: To compare a group of fetuses whose mothers had acute or recent toxoplasmosis with a group of fetuses whose mothers had no systemic disease, analyzing the presence of changes in endocardial refringence. METHODS: This study assessed 91 fetuses of mothers diagnosed with acute or recent toxoplasmosis, detected by seroconversion or the presence of elevated IgM and IgG titers, confirmed through the IgM-capture ELISA. They were compared with a control group comprising 182 fetuses selected from a low-risk population participating in a prenatal screening program for heart diseases. RESULTS: No significant difference was observed between the mean gestational (29.2+/-4.6 weeks; 29.2+/-4.6 weeks) and maternal (25.7+/-6.7 years; 26+/-5.4 years) ages in the 2 groups. Areas of endocardial hyperechogenicity were observed in 69 fetuses whose mothers had toxoplasmosis (75.8%) and in only 6 fetuses of the control group (3.3%) (P<0.001). In 52 patients of the group studied (75.4%), endocardial hyperrefringence was diffuse, and, in 17 (24.3%), it was focal. In the control group, focal distribution was observed in 5 fetuses (83.3%). CONCLUSION: The prenatal echocardiographic image of focal or diffuse endocardial hyperrefringence is more prevalent in pregnancies with maternal toxoplasmosis than in the healthy ones, and an association between fetal endocardial hyperechogenicity and maternal disease exists.