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[A case of congenital toxoplasmosis confirmed by detection of Toxoplasma gondii in placenta].

We report a case of congenital toxoplasmosis with a prenatal diagnosis of fetal hydrocephalus. A CT scan performed at birth revealed ventricular dilation with calcification. The serum and CSF Toxoplasma specific IgM were elevated. The diagnosis was confirmed by the presence of Toxoplasma cysts in the placenta, and detection of the Toxoplasma SAG1 gene by a polymerase chain reaction (PCR) (placenta, positive; CSF, negative). Signs of active central nervous system infection, such as the decreased CSF glucose, and elevated CSF protein, neuron specific enolase and LDH, resolved after initiation of treatment with pyrimethamine and sulfazoxine. A PCR test using the placental tissue may be useful for the rapid diagnosis of congenital toxoplasmosis.

Adult↗

Impact of visual impairment on measures of cognitive function for children with congenital toxoplasmosis: implications for compensatory intervention strategies.

OBJECTIVES: The purpose of this work was to determine whether visual impairment caused by toxoplasmic chorioretinitis is associated with impaired performance of specific tasks on standardized tests of cognitive function. If so, then we worked to determine whether there are patterns in these difficulties that provide a logical basis for development of measures of cognitive function independent of visual impairment and compensatory intervention strategies to facilitate learning for such children. METHODS: Sixty-four children with congenital toxoplasmosis with intelligence quotient scores > or = 50 and visual acuity sufficient to cooperate with all of the intelligence quotient subscales had assessments of their vision, appearance of their retinas, and cognitive testing performed between 3.5 and 5 years of age. These evaluations took place between 1981 and 1998 as part of a longitudinal study to determine outcome of congenital toxoplasmosis. Children were evaluated at 3.5 or 5 (37 children) or both 3.5 and 5 (27 children) years of age. Cognitive function was measured using the Wechsler Preschool and Primary Scale of Intelligence-Revised. Wechsler Preschool and Primary Scale of Intelligence-Revised scale scores were compared for children grouped as those children who had normal visual acuity in their best eye (group 1), and those who had impaired vision in their best eye (acuity < 20/40) because of macular disease (group 2). Demographic characteristics were compared for children in the 2 groups. Test scores were compared between groups using all of the 3.5-year-old visits, all of the 5-year-old visits, and using each child's "last" visit (ie, using the 5-year-old test results when a child was tested at both 3.5 and 5 years of age or only at 5 years, otherwise using the 3.5-year-old test results). The results were similar and, therefore, only the results from the last analysis are reported here. RESULTS: There were 48 children with normal visual acuity in their best eye (group 1) and 16 children with impaired vision because of macular involvement in their best eye (group 2). Ethnicity and socioeconomic scores were similar. There was a significantly greater proportion of males in group 2 compared with group 1 (81% vs 46%). There was no significant diminution in Wechsler Preschool and Primary Scale of Intelligence-Revised test scores between 3.5 and 5 years of age for the 27 children tested at both of these ages. Verbal intelligence quotient, performance intelligence quotient, full-scale intelligence quotient scores, and all of the scaled scores except arithmetic and block design were significantly lower for children in group 2 compared with group 1. The majority of the differences remained statistically significant or borderline significant after adjusting for gender. However, the difference in overall verbal scores does not remain statistically significant. Mean +/- SD verbal (98 +/- 20) and performance (95 +/- 17) intelligence quotients were not significantly different for children in group 1. However, verbal (88 +/- 13) and performance intelligence quotients (78 +/- 17) were significantly different for children in group 2. For children in group 2, their lowest scale scores were in object assembly, geometric design, mazes, and picture completion, all timed tests that involved visual discrimination of linear forms with small intersecting lines. In the 2 scales scored that did not differ between groups 1 and 2, arithmetic and block design, timing and vision but not linear forms were components of the tasks. Children with monocular and binocular normal visual acuity did not differ in verbal, performance, or full-scale intelligence quotients or any of the subscale tests. Difficulty with sight or concomitant neurologic involvement also seemed to impact the ability to acquire information, comprehension skills, and vocabulary and performance in similarities testing. After controlling for gender, however, these differences were diminished, and there were no longer differences in overall verbal scores. As noted above, results were generally similar when all of the tests for 3.5-year-olds or 5-year-olds were analyzed separately. At the 3.5-year visit there were fewer significant differences between the 2 groups for the verbal components than at the 5-year visit. CONCLUSIONS: In children with congenital toxoplasmosis and bilateral macular disease (group 2) because of toxoplasmic chorioretinitis, scaled scores were lowest on timed tests that require discrimination of fine intersecting lines. Although the severity of ocular and neurologic involvement is often congruent in children with congenital toxoplasmosis, ophthalmologic involvement seems to account for certain specific limitations on tests of cognitive function. Children with such visual impairment compensate with higher verbal skills, but their verbal scores are still less than those of children with normal vision, and in some cases significantly so, indicating that vision impairment might affect other aspects of cognitive testing. Patterns of difficulties noted in the subscales indicate that certain compensatory intervention strategies to facilitate learning and performance may be particularly helpful for children with these impairments. These patterns also provide a basis for the development of measures of cognitive function independent of visual impairment.

Child, Preschool↗

Risk factors for Toxoplasma gondii infection in mothers of infants with congenital toxoplasmosis: Implications for prenatal management and screening.

OBJECTIVE: The purpose of this study was to determine whether demographic characteristics, history of exposure to recognized transmission vehicles, or illness that was compatible with acute toxoplasmosis during gestation identified most mothers of infants with congenital toxoplasmosis. STUDY DESIGN: Mothers of 131 infants and children who were referred to a national study of treatment for congenital toxoplasmosis were characterized demographically and questioned concerning exposure to recognized risk factors or illness. RESULTS: No broad demographic features identified populations that were at risk. Only 48% of mothers recognized epidemiologic risk factors (direct or indirect exposure to raw/undercooked meat or to cat excrement) or gestational illnesses that were compatible with acute acquired toxoplasmosis during pregnancy. CONCLUSION: Maternal risk factors or compatible illnesses were recognized in retrospect by fewer than one half of North American mothers of infants with toxoplasmosis. Educational programs might have prevented acquisition of Toxoplasma gondii by those mothers who had clear exposure risks. However, only systematic serologic screening of all pregnant women at prenatal visits or of all newborn infants at birth would prevent or detect a higher proportion of these congenital infections.

Adult↗

[Congenital toxoplasmosis. Tolerability of the sulfadoxine-pyrimethamine combination. 24 cases].

The pyrimethamine-sulfadoxine combination, active against acute toxoplasmosis in the mouse, was administered to 24 children with congenital toxoplasmosis in doses of 500 mg sulfadoxine and 25 mg pyrimethamine per 20 kg bodyweight once every fortnight. The drug appeared to be as effective as other sulfonamide-pyrimethamine combinations. It was generally well tolerated and was withdrawn in only 3 patients on account of minor side-effects. Giving pyrimethamine-sulfadoxine together with folinic acid is a much simpler treatment of congenital toxoplasmosis than the usual ones.

Child, Preschool↗

[Congenital toxoplasmosis with hydranencephaly. A case report (author's transl)].

Hydranencephaly is an uncommon finding in congenital toxoplasmosis. The authors report a new case and emphasize the toxoplasmic etiology of this malformation, the possibility of normal neurologic examination at birth, and the usefulness of cranial transillumination whenever congenital toxoplasmosis is suspected in a neonate.

Anencephaly↗

Evaluation of a commercial IgG/IgM Western blot assay for early postnatal diagnosis of congenital toxoplasmosis.

The aim of this study was to evaluate a commercial Western blot IgG/IgM assay for use in the early serological diagnosis of congenital toxoplasmosis. This assay compares the immunological profile of mother and infant and allows differentiation between passive transmitted maternal antibodies and newly synthesized antibodies of the infant within the first 3 months of life. Over a 6-year period (1995-2001), the sera from 169 mothers and their 175 offspring (6 had twins) were examined for specific anti- Toxoplasma gondii IgG, IgM and IgA antibodies with an enzyme-linked immunosorbent assay or an immunosorbent agglutination assay. All mothers had primary Toxoplasma infection during pregnancy. Serological and clinical follow-up of the infants during the first year of life confirmed 36 cases of congenital toxoplasmosis. In 139 cases, infection could be ruled out. Three hundred fifty-one paired samples from 175 mother-child pairs were tested retrospectively for IgG and IgM patterns by Toxoplasma Western blot IgG/IgM (LDBIO Diagnostics, France). The results of conventional serological analysis (immunosorbent agglutination assay or enzyme-linked immunosorbent assay) to detect IgM or IgA were compared with the results of the Toxoplasma Western blot IgG/IgM on samples obtained within the first 3 months of life. The performance of the combination of the two methods was also assessed. At birth, the sensitivity values of conventional serological analysis and the Toxoplasma Western blot were 52% and 67%, with specificity values being 99% and 96%, respectively. Combination of the Western blot and conventional serological analysis increased the sensitivity at birth to 78% and within the first 3 months of life to 85%. Overall, the combination of both methods detected 94% of congenital infections. Therefore, this commercial Western blot represents a useful tool for early postnatal diagnosis of congenital toxoplasmosis.

Animals↗

[Morphological study of 2 cases of congenital toxoplasmosis].

A morphological study of two cases of acute generalized congenital toxoplasmosis has shown that in one case the most heavily involved organ was the heart (focal necrotic myocarditis), in addition to some changes in the central nervous system (leptomeningitis), and in the other case, the most affected organ was the cerebrum (focal necrotic encephalitis). In both cases, in almost all organs, there were degenerative and reactive changes. Toxoplasma was found in necrotic foci of the myocardium and the brain. Some basic views concerning a special vulnerability of the central nervous system in toxoplasmosis are put forward. The basic fact is that the explanation for the infection of exposed fetuses lies in the condition of the immune system (in the degree of its development and activity), especially regarding certain localizations of changes in the organs with a less developed activity of the local immune system.

Autopsy↗

[Congenital toxoplasmosis--in prospective studies].

In the action of prevention of congenital toxoplasmosis prospective studies were carried out of women at reproductive age for detection of antibodies to Toxoplasma gondii. Women seronegative before pregnancy were subjected during pregnancy to three tests for the presence of these antibodies in the 1st, 2nd and 3rd trimester. After development of seroconversion in pregnancy further observation was conducted which made possible the diagnosis of active primary infection in pregnancy in 12 cases. Prophylactic treatment of the mothers was administered and the newborns were observed for the consequences of intrauterine infection.

Animals↗

Congenital toxoplasmosis associated with transient monoclonal IgGl-lambda gammopathy.

A congenital toxoplasmosis infection was diagnosed in a newborn child with severe oculo-central nervous system involvement. Antibodies to toxoplasma became detectable in the mother's serum during pregnancy, and at delivery both mother and child had high titers of IgG toxoplasma antibody. A normal protein profile was found in the serum of the mother, but transient monoclonal gammopathy (IgG1- lambda ) was found in the child. A specific antiidiotype serum raised against this monoclonal immunoglobulin failed to react with the serum of the mother and with other sera positive for toxoplasma antibody. The toxoplasma antibody in the serum of the newborn child was restricted to IgG-lambda, but no evidence was found that the monoclonal fraction was responsible for the antibody activity.

Animals↗

Long term ocular and neurological involvement in severe congenital toxoplasmosis.

AIMS: This study was set up to determine the long term ocular and systemic sequelae in patients with severe congenital toxoplasmosis. METHODS: Cross sectional and retrospective study of 17 patients with severe congenital toxoplasmosis. RESULTS: In addition to chorioretinitis (100%), the most common abnormal ocular features were optic nerve atrophy (83%), visual acuity of less than 0.1 (85%), strabismus, and microphthalmos. In 50% of cases we observed iridic abnormalities and about 40% developed a cataract. Overt endocrinological disease, diagnosed in five of 15 patients, included panhypopituitarism (n = 2), gonadal failure with dwarfism (n = 1), precocious puberty with dwarfism and thyroid deficiency (n = 1), and diabetes mellitus and thyroid deficiency (n = 1). The observed endocrinological involvement was associated in all cases with obstructive hydrocephalus with a dilated third ventricle and optic nerve atrophy. CONCLUSION: The recognition of long term ocular, neurological, and endocrinological sequelae of congenital toxoplasmosis is important for medical management of these severely handicapped patients.

Adolescent↗

Phenotypes and functions of lymphocytes in congenital toxoplasmosis.

Comparisons of lymphocyte surface phenotypes and functions were made among 25 pediatric patients with congenital toxoplasmosis (ages 1 month to 5 years) and 24 uninfected babies, a baby with postnatally acquired infection, and 6 uninfected, 7 recently infected, and 6 chronically infected adults. Percentages of lymphocytes with B1, T11, T3, T4, T8, T6, B4, Ia, NKH phenotypes and T4 to T8 ratios of infected and uninfected babies were the same (p greater than 0.05). Lymphocytes from congenitally infected babies had lower blastogenic responses (mean stimulation index [SI] = 5) to Toxoplasma lysate antigens (TLA) than lymphocytes from adult control groups with recent and chronic infection (Mean SIs = 32, 72; p less than 0.001). Compared to infected adults, congenitally infected children had similar or greater responses to concanavalin A (mean SIs = 94; 118, 76, p greater than 0.05) and in mixed leukocyte culture (mean SIs = 63; 22, 26, p greater than 0.05). For symptomatic babies, low blastogenic response to TLA correlated with more severe disease at presentation (p = 0.002). Lymphocyte blastogenic responses to TLA were increased for most children when they were older than 15 months, but responses remained less than adult levels for 9 of the 17 older children studied. There was no correlation between concomitant serum pyrimethamine levels and lymphocyte blastogenic responses to TLA. Pyrimethamine and sulfonamide treatment in vitro and in vivo did not alter lymphocyte response to TLA. Lymphocytes from congenitally infected babies failed to produce either gamma interferon or Interleukin 2 when cultured with TLA. In contrast, they produced these lymphokines when cultured with concanavalin A or phytohemagglutinin. Specific deficits in cell-mediated immune responses to TLA may account for the significant organ damage that occurs in infants and children with congenital toxoplasmosis.

Adult↗

Diagnosis of congenital toxoplasmosis at birth: what is the value of testing for IgM and IgA?

UNLABELLED: Recommendations vary on the best combination of tests to use for the diagnosis of subclinical congenital toxoplasmosis at birth. The diagnostic accuracy of IgM and IgA tests was assessed in the context of routine clinical practice on 233 newborns with congenital toxoplasmosis and 661 healthy controls. IgM/IgA sensibility and specificity were compared in cord and postnatal samples. Both tests were considerably more specific in neonatal blood (IgM: 98%; IgA: 100%) than in cordblood (IgM: 85%; IgA: 88%). Sensitivity for IgM and IgA was not significantly different in neonatal blood (61% and 60%, respectively) and cord blood (67% and 54%, respectively). Combining IgM and IgA increased the overall sensitivity to 73% without any significant loss in specificity (98%). The influence of the date of maternal infection on the sensitivity and negative predictive value was also clearly demonstrated. CONCLUSION: Because of their relatively low cost compared to more sophisticated methods, IgM and IgA tests should remain the main method for the routine diagnosis of congenital toxoplasmosis although follow up is essential to identify the Ca. 25% of infected children who are missed at birth on the basis of these tests.

Agglutination Tests↗

Prediction of congenital toxoplasmosis by polymerase chain reaction analysis of amniotic fluid.

OBJECTIVE: To determine the accuracy of polymerase chain reaction (PCR) analysis of amniotic fluid for fetal toxoplasmosis according to clinical predictors of outcome and study centre. DESIGN: Prospective cohort study. SETTING: Nine European centres. POPULATION: Women with suspected toxoplasma infection identified by prenatal screening. METHODS: Logistic regression was used to examine the effects of gestational age at maternal seroconversion, treatment and timing of amniocentesis, on PCR accuracy, and to calculate the post-test probability of congenital toxoplasmosis. MAIN OUTCOME MEASURES: Infants had congenital toxoplasmosis if specific IgG persisted beyond 11.5 months. Uninfected infants had undetectable IgG in the absence of anti-toxoplasma treatment. RESULTS: Of 593 PCR results, 64 were positive (57 confirmed infected), and 529 were negative (23 confirmed infected). The likelihood ratio for a positive PCR result decreased significantly with trimester at seroconversion, but did not change significantly for a negative result. Weak associations were detected between sensitivity and, inversely, with specificity, and gestational age at maternal seroconversion. There was no significant association between sensitivity and centre, type or duration of treatment, or timing of amniocentesis. Specificity differed significantly between centres (P < 0.001). The change in pre- to post-test probability of infection was maximal for a positive PCR after first trimester seroconversion, affecting 1% of women tested, and a negative PCR after third trimester seroconversion, affecting half the women tested. CONCLUSIONS: Prediction of the risk of congenital toxoplasmosis should combine estimates of test accuracy and maternal-fetal transmission, which take account of the gestational age at which the mother seroconverted. Local laboratory standards will affect the generalisability of these results.

Amniotic Fluid↗

[Screening for congenital toxoplasmosis: pregnancy outcome after prenatal diagnosis in 211 cases].

OBJECTIVE: To emphasize the importance of follow-up after birth of infants with an antenatal diagnosis of congenital toxoplasmosis. METHODS: Retrospective study from July 1987 through January 31 1995 on 211 women (214 fetuses) who had undergone ovular biopsy for toxoplasmosis seroconversion during pregnancy. RESULTS: Antenatal diagnosis was positive in 13 patients (6.2%). Four pregnancies were terminated during the second trimester. Delivery was triggered at 37 weeks gestation in one woman and in 8 others pregnancy was continued with Fansidar. All infants were born live with infraclinic disease. Two fetal deaths related to biopsy technique occurred (0.95%) and one pregnancy was terminated before the results had been obtained. Only 21.3% of the patients were delivered in our unit. A total of 197 infants were delivered with a negative antenatal diagnosis: 93 were healthy, 5 had congenital toxoplasmosis, 1 died at 3 months and 98 had no or incomplete follow-up. CONCLUSION: Incomplete post-natal follow-up is in contradiction with the excellent performance of antenatal diagnosis of congenital toxoplasmosis. Greater care is needed, especially since now only an amniocentisis is required to detect the parasite genome with polymerase chain reaction.

Adolescent↗

Infants potentially at risk for congenital toxoplasmosis: a prospective study.

Fifty-two children were selected as being potentially at risk for congenital toxoplasmosis by serologic testing of 8,043 pregnant women in the Oslo area. These infants were then studied during the neonatal period and subsequently followed up for three years. Three were found to be congenitally infected with Toxoplasma gondii, and one infant was dysmature at birth. The diagnosis was confirmed by persistent dye-test antibodies and by recovery of parasites in placenta and/or amniotic fluid. The Toxoplasma indirect fluorescent IgM-antibody test remained negative, while measurements of cord IgM and IgA levels and serial estimations of specific antibody load supported an early diagnosis. The specific cell-mediated immunity, as measured by the in vitro lymphocyte stimulation test, turned positive at 1 year of age and then increased markedly during the second and third years. The lymphocyte responses of the uninfected children, however, remained negative. The infected children received pyrimethamine/sulfadiazine treatment during their first year, with no clinical signs of congenital toxoplasmosis.

Antibodies↗

[Congenital toxoplasmosis: transmission to the fetus of a pre-pregnancy maternal infection].

It has been established that maternal immunity developing before conception protects the fetus from congenital toxoplasmosis. We observed a case of congenital toxoplasmosis consecutive to a maternal toxoplasma infection that had preceded pregnancy. A woman with normal immune system developed toxoplasmosis 2 months before conceiving. No treatment was given to this prepregnancy seroconverted patient. At 25 weeks of amenorrhoea, the ultrasound examination showed a fetal cerebral ventricular dilatation. Amniocentesis and cordocentesis showed fetal toxoplasmosis infection. Fetopathologic examination confirmed the diagnosis of cerebral toxoplasmosis. The pathophysiology of maternal-fetal toxoplasma transmission and the role played by maternal immunodeficiency are discussed. This exceptional case-report showed the difficulties of the management in patients with 3-month pre-pregnancy toxoplasmosis and its practical implications.

Abortion, Therapeutic↗

Association between prenatal treatment and clinical manifestations of congenital toxoplasmosis in infancy: a cohort study in 13 European centres.

AIM: To determine the effectiveness of prenatal treatment for clinical manifestations of congenital toxoplasmosis. METHODS: We prospectively identified 255 live-born infants with congenital toxoplasmosis using prenatal or neonatal screening. We determined the effect of prenatal treatment on the risks of intracranial or ocular lesions in infancy, accounting for gestational age at maternal seroconversion. RESULTS: Prenatal treatment within 4 wk of seroconversion reduced the risk of intracranial lesions compared with no treatment (odds ratio, OR 0.28; 95% CI: 0.08-0.75), but there was no significant effect when initiated after 4 wk (OR 0.76; 95% CI: 0.35-1.59; overall p-value 0.19). Compared to spiramycin alone, no treatment doubled the risk of intracranial lesions (OR 2.33; 95% CI: 1.04-5.50), but the risk did not differ with pyrimethamine-sulphonamide treatment (overall p-value 0.52). There was no consistent relationship between the type or timing of treatment and the risk of ocular lesions. Gestational age at maternal seroconversion was inversely associated with the risk of intracranial but not ocular lesions. CONCLUSION: Only early versus no prenatal treatment for intracranial lesions showed a statistically significant benefit. A large randomized controlled trial and/or meta-analysis of individual patient data from cohort studies is required to confirm these findings.

Adult↗