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Neonatal screening for congenital toxoplasmosis in the Poznań region of Poland by analysis of Toxoplasma gondii-specific IgM antibodies eluted from filter paper blood spots.

OBJECTIVES: The aims of the study were to determine the prevalence of congenital toxoplasmosis at birth in the Poznań region of Poland, the value of the serologic examination of filter paper blood specimens collected from newborns for the diagnosis of congenital Toxoplasma infection and the duration of anti-Toxoplasma-specific IgM antibodies in infants' sera. MATERIALS AND METHODS: All neonates born in the maternity wards of the University Hospital of Gynaecology and Obstetrics in Poznań and in 10 selected obstetrics wards in the district hospitals were included. Blood samples were collected on filter paper cards, between the first and sixth day of life, screened for anti-Toxoplasma-specific IgM antibodies by an immunocapture enzyme-linked immunosorbent assay and if positive further analyzed for specific IgG and IgA antibodies. RESULTS: Between June, 1996, and October, 1998, filter paper samples from 27,516 liveborn infants were tested, which constituted approximately 75% of all births and 83% of liveborn neonates from the Poznań region. Anti-T. gondii-specific IgM antibodies were found in 13 newborns, equivalent to a prevalence of Toxoplasma-specific IgM in newborns of 1 per 2,117 liveborn children (0.47 per 1,000) or 1 per 870 children (1.15 per 1,000) born to seronegative women at risk of primary T. gondii infection during pregnancy. We identified two congenitally infected infants who were IgM-negative at birth, had a classic triad of clinical symptoms during the first year of life and had high levels of specific IgG. The birth prevalence of congenital toxoplasmosis in the Poznań region was at least 1 per 1,834 live births (0.55 per 1,000) or 1 per 754 live neonates born to seronegative women (1.33 per 1,000). The sensitivity of the IgM assay on eluate from filter paper was not more than 86.7%, and the mean duration of IgM detectable by enzyme-linked immunosorbent assay in serum samples was the first 4.8 weeks of life. CONCLUSION: In Poland the screening for congenital toxoplasmosis detecting one case per each 2,000 live births could be considered for inclusion in existing national neonatal screening programs for phenylketonuria and congenital hypothyroidism.

Animals↗

Congenital toxoplasmosis: a large survey in western Australia.

OBJECTIVE: To determine the birth prevalence of congenital toxoplasmosis in Western Australia. DESIGN: A prospective serological study of randomly selected pregnant women and their newborn infants. Paired sera collected from the mothers at their first antenatal visit and cord blood specimens taken from their infants were tested for toxoplasmosis by the direct agglutination test and Toxoplasma IgM-capture enzyme-linked immunosorbent assay. SETTING: A major Perth metropolitan obstetric teaching hospital where approximately one-quarter of infants born in Western Australia during January 1986 to December 1989 inclusive were delivered. PARTICIPANTS: Sera were obtained from 10,207 pregnant women presenting for routine clinical evaluation at their first antenatal visit. Cord blood specimens were taken from 18,908 infants; 7523 of these could be paired to maternal specimens. MAIN OUTCOME MEASURES: Maternal infection was indicated in cases where Toxoplasma specific IgM antibody was present or where an initial maternal specimen gave negative results for Toxoplasma antibody but the paired cord blood specimen gave positive results. Toxoplasma specific IgM antibody in a cord blood specimen indicated fetal infection. RESULTS: Of the 10,207 women 3544 (35%) were Toxoplasma immune at their first antenatal visit; in 11 Toxoplasma specific IgM antibody was detected. There was no serological or clinical evidence of congenital toxoplasmosis in any of the offspring of these 11 mothers. The rate of maternal infection in susceptible pregnancies was 1.6 per 1000; the maternal-fetal transmission rate was estimated to be no greater than 24%. Three of the 18,908 cord blood specimens tested gave positive results for Toxoplasma specific IgM antibody giving a birth prevalence of congenital infection of 0.23 per 1000 births to non-immune mothers. There were no clinical features of congenital infection in these three infants but they will require long-term follow-up. Thirteen of the 14 mothers infected during pregnancy were interviewed retrospectively and in only three was a known risk factor for infection present. CONCLUSIONS: a toxoplasmosis screening programme for pregnant mothers is not justifiable in Western Australia. A public education programme is also likely to have limitations.

Agglutination Tests↗

Congenital toxoplasmosis.

Toxoplasma gondii, a parasite, has three modes of transmission: oral intake of raw or undercooked meat or contaminated fruits and vegetables, ingestion of materials contaminated with cat feces, and transplacental infection. The focus of this article is congenital toxoplasmosis, which is transmitted to the fetus across the placenta. When primary infection of the mother occurs during pregnancy, there is a 40 percent chance of fetal infection; rate of transmission and severity of infection are related to gestational age at the time of infection. The brain and retina are often affected, and there can be a wide range of clinical disease. Amniocentesis or cordocentesis provides the most accurate diagnosis. At birth, 80-90 percent of infants with congenital toxoplasmosis are asymptomatic. But further testing may reveal retinal and central nervous system abnormalities, and there is a risk of long-term sequelae. Chorioretinitis, hydrocephalus, intracranial calcifications, and convulsions are the typical presentation of classic congenital toxoplasmosis. Serology is the most common method of diagnosing neonatal infection, but more complex tests are also utilized. The prognosis for the untreated infant is poor; however, when antibiotic therapy is started early, the rate of sequelae is reduced significantly.

Animals↗

The use of an IgM immunosorbent agglutination assay to diagnose congenital toxoplasmosis.

An IgM immunosorbent agglutination assay (ISAGA) was compared with a standard ELISA IgM test for the diagnosis of congenital toxoplasmosis. It was more sensitive, detecting all of five mothers of infected babies whereas the IgM ELISA was positive in two of three mothers tested at delivery and neither of two mothers referred 10-12 months after delivery. Five women infected in a previous pregnancy had IgM detectable by ISAGA in a subsequent pregnancy. The assays were comparable when sera from patients with past infection were tested or following toxoplasma-associated miscarriage or abortion. Four cord sera from congenitally-infected babies were positive by the ISAGA but only three of these were positive by ELISA for IgM. The ISAGA also detected IgM in another four sera from congenitally-infected babies referred late (10-18 months old); none were IgM positive by ELISA. The increased sensitivity of the ISAGA is an improvement in the diagnosis of congenital toxoplasmosis.

Agglutination Tests↗

Detection of anti-toxoplasma immunoglobulin A antibodies by Platelia-Toxo IgA directed against P30 and by IMx Toxo IgA for diagnosis of acquired and congenital toxoplasmosis.

Platelia-Toxo IgA and IMx Toxo IgA assays were used with 260 serum samples, of which 93 were from seroconverted patients, 58 were from 21 congenitally infected children, and 109 were from uninfected patients, to detect anti-P30 immunoglobulin A antibodies. Because of its enhanced sensitivity, Platelia-Toxo IgA is more efficient in diagnosing acute or congenital toxoplasmosis. IMx Toxo IgA must not be used to diagnose congenital toxoplasmosis.

Animals↗

Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment. Danish Congenital Toxoplasmosis Study Group .

BACKGROUND: The best method for prevention and control of congenital toxoplasma infection is uncertain. Prenatal screening is done in Austria and France, but the effect of treatment during pregnancy is not well documented. The aim of our study was to find out the maternofetal transmission rate and outcome in infants born to mothers who were not treated during pregnancy. METHODS: We analysed 89873 eluates from phenylketonuria (PKU) cards from neonates and paired first-trimester serum samples from the mothers for specific IgG antibodies to Toxoplasma gondii. Children born to mothers who seroconverted during pregnancy were followed-up clinically and serologically to 12 months of age. In addition, 21144 PKU cards were analysed for toxoplasma-specific IgM antibodies during the last 12 months of the study. FINDINGS: In 24989 (27.8%) cases both the PKU eluate and the first-trimester samples were IgG positive, which indicates previous maternal infection. 139 of the 64884 seronegative women acquired toxoplasma infection during pregnancy and gave birth to 141 infants (two sets of twins). 27 of these children were diagnosed with congenital toxoplasma infection. The transmission rate was 19.4% (95% CI 13.2-27.0). Clinical signs and symptoms were found in four (15%) of the 27 children. The additional analysis for toxoplasma-specific IgM antibodies from the PKU card identified seven of nine children with congenital toxoplasma infection. The false-positive rate for the IgM test was 0.19 per 1000, and no false-negatives were found. INTERPRETATION: The risks of transmission of infection and of disease in the infant are low in an area with a low risk of toxoplasma infection. A neonatal screening programme based on detection of toxoplasma-specific IgM antibodies alone will identify between 70% and 80% of cases of congenital toxoplasmosis.

Adult↗

[Congenital toxoplasmosis. Report of a case treated with spiramycin in the 24th week of pregnancy].

The Authors present one case of congenital toxoplasmosis; it was sustained by a primary maternal infection, contracted at the XXIII week of gestation. Even if we started the treatment with spiramycin at the XXIV week of gestation, both the prenatal ultrasound examination of the fetus, and the postnatal investigation of the newborn, showed that the young patient was affected by a severe form of congenital toxoplasmosis.

Female↗

[Detection of congenital toxoplasmosis in utero with a polymerase chain reaction on amniotic fluid].

To establish a prenatal diagnosis of congenital toxoplasmosis the PCR test was done on amniotic fluids from 47 women suspected of primary Toxoplasma infection during pregnancy. Fragments of Toxoplasma B1 gene were found in 5 examined samples. Positive tests were confirmed by mouse inoculation or by serologic testing of newborns. It was concluded that the PCR performed on amniotic fluid should be recommended for the prenatal diagnosis of congenital toxoplasmosis, however, negative results of the test can not rule out congenital infection.

Amniotic Fluid↗

Prevention of congenital toxoplasmosis in Szeged, Hungary.

BACKGROUND: Toxoplasma gondii infection of the fetus can only be discovered or prevented by the appropriate serological screening and subsequent treatment of the mother and her offspring. In Hungary, there is no obligatory toxoplasma screening for pregnant women and both the reporting and follow-up of congenital toxoplasmosis cases is limited. In 1987 we started a systematic study in the Szeged region of Hungary, in which all pregnant women were screened and appropriate treatment given to all mothers and their offspring where congenital toxoplasmosis was suspected. METHODS: All pregnant women were routinely screened within the first 16 weeks of gestation for toxoplasma antibodies by complement fixation test (CFT). Seronegative cases were retested for possible seroconversion every second month. Patients with CFT titres > or = 1:256 were retested for anti-P30 immunoglobulin A (IgA), IgM and IgG antibodies by ELISA and/or SDS-PAGE-Western immunoblot in order to distinguish the acute and chronic phases of the infection. RESULTS: Up to the end of 1994, the sera of 17,735 gravidae were screened. Ten women were found to have seroconverted during pregnancy and 78 had high initial antibody levels accompanied by anti-P30 IgA antibodies at the very first screening. These two groups together were considered as definitely (10) or possibly (78) infected with Toxoplasma during pregnancy and were treated with Spiramycin. All of their offspring were also treated for one month and followed-up by systematic serological and clinical screening for 2 years. No congenital toxoplasmosis was found in any of the offspring. CONCLUSIONS: Antenatal, early diagnosis and treatment of toxoplasmosis in mothers, together with treatment and follow-up of their offspring, may considerably reduce the incidence of the disease in the offspring.

Animals↗

[Two cases of congenital toxoplasmosis with a central nervous system damage--delayed diagnosis].

OBJECTIVES: The intrauterine toxoplasma gondii infection is linked with a high risk of central nervous system/CNS/damage in the fetus. Why, despite the wide knowledge of this neurodegenerative disease prophylaxis and therapy, do we still meet neonates with the CNS damage? DESIGN, MATERIALS AND METHODS: Authors present two cases of congenital toxoplasmosis with the CNS involvement. RESULTS: One of the cases was identified as the internal hydrocephalus during a prenatal ultrasound examination but no further diagnostics tests were undertaken. The congenital toxoplasmosis and severe CNS damage was diagnosed post delivery. In the other case some clinical symptoms of the CNS infection appeared in the neonatal period. Now this patient is eight months old and presenting mild motor developmental delays. CONCLUSIONS: 1. There are many clinical symptoms of the congenital toxoplasmosis, that can occur in the prenatal/case 1/and postnatal/case 2/period. 2. No serologic tests for toxoplasmosis were performed in mothers during pregnancy, what delays treatment and diagnosis of sick children. 3. Fetus presenting the CNS anomalies identified during ultrasound examinations should be immediately diagnosed.

Female↗

Pyrimethamine-sulfadoxine treatment of congenital toxoplasmosis: follow-up of 78 cases between 1980 and 1997. Reims Toxoplasmosis Group.

UNLABELLED: The purpose of this study was to determine the clinical and immunological outcome of 78 children with congenital toxoplasmosis treated with the pyrimethamine-sulfadoxine combination between 1980 and 1997. METHODS: Children were divided into 3 groups according to the initial duration of treatment (always including folinic acid, 5 mg/week by mouth), as follows: pyrimethamine (1.25 mg/kg every 15 d) + sulfadoxine (25 mg/kg every 15 d) for 12 months (Group 1, 47 children), or for 24 months, with or without prenatal therapy (respectively, Group 2, 19 children, and Group 3, 12 children). RESULTS: Chorioretinitis occurred in 23% of these 78 children. Four children had unilateral blindness, 1 had mild epileptic fits and 1 had psychomotor retardation. The lowest rate of sequelae were in Groups 2 and 3. Immunological rebounds, generally without clinical repercussions, occurred frequently (90% of cases on average) during, or more often after therapy, regardless of the treatment duration. Treatment was always well tolerated. CONCLUSIONS: Our current treatment strategy for congenital toxoplasmosis consists of a 24-month course of pyrimethamine-sulfadoxine (Fansidar) combined with folinic acid (Lederfoline). If the prenatal diagnosis is positive, we also prescribe this treatment to the mother until delivery. This combination offers satisfactory compliance, adequate serum concentrations, and good preventive efficacy.

Adolescent↗

Congenital toxoplasmosis: systematic review of evidence of efficacy of treatment in pregnancy.

OBJECTIVE: To summarise the evidence that treating toxoplasmosis in pregnancy reduces the risk of congenital toxoplasma infection and improves infant outcomes. DESIGN: Systematic review of studies comparing at least two concurrent groups of pregnant women with proved or likely acute toxoplasma infection in which treatments were compared with no treatment and outcomes in the children were reported. SUBJECTS: Studies were identified from Medline (1966-97), Pascal (1990-7), Embase (1993-7), and Biological abstracts (1993-5) plus contact with experts in the field, including the European Research Network on Congenital Toxoplasmosis. MAIN OUTCOME MEASURE: Proportion of infected children at 1 year born to infected pregnant women who were or were not treated. RESULTS: Out of 2591 papers identified, nine met the inclusion criteria. There were no randomised comparisons, and control groups were generally not directly comparable with the treatment groups. Congenital infection was common in treated groups. five studies showed that treatment was effective and four that it was not. CONCLUSION: It is unclear whether antenatal treatment in women with presumed toxoplasmosis reduces congenital transmission of Toxoplasma gondii. Screening is expensive, so the effects of treatment and impact of screening programmes need to be evaluated. In countries where screening or treatment is not routine, these technologies should not be introduced outside carefully controlled trials.

Acute Disease↗

Congenital toxoplasmosis: is screening desirable?

Toxoplasmosis, a disease caused by the parasite Toxoplasma gondii, is a worldwide health problem. Infection of a pregnant woman can result in severe fetal morbidity and even death. Moreover, there is increasing awareness that congenital toxoplasmosis can cause blindness, epilepsy and other abnormalities in children and adults. Congenital toxoplasmosis can only be prevented by giving information on how to avoid the infection during pregnancy or by routine serologic screening of pregnant women to identify a recent toxoplasma infection that would allow a timely decision for antibiotic treatment and prenatal diagnosis. Advice to pregnant women to apply hygienic measures during pregnancy can reduce with 63% the toxoplasma infection rate during pregnancy and should therefore become standard obstetrical care. Adequate serological screening for toxoplasmosis is possible and allows selection of patients at high risk for delivering a congenitally infected child. Prenatal diagnosis is accurate in diagnosing correctly infected fetuses around the 20th week of gestation. Whether or not serologic screening for toxoplasmosis should be combined with primary prevention will depend on the incidence of congenital toxoplasmosis in a given geographic area.

Female↗