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Discrimination between patients with acquired toxoplasmosis and congenital toxoplasmosis on the basis of the immune response to parasite antigens.

Many persons infected with Toxoplasma gondii develop ocular lesions. Immunologic parameters in the response to T. gondii were evaluated in infected persons with and without ocular lesions and in noninfected controls. Subjects were divided into groups on the basis of presence of serum antibodies to T. gondii, presence of ocular lesions, and clinical history. Production of interleukin-2 and interferon-gamma by peripheral blood mononuclear cells from patients with probable congenital toxoplasmosis was decreased, compared with that in persons with presumed acquired infection. Cell proliferation and delayed-type skin reaction induced by soluble toxoplasma tachyzoite antigen followed the same pattern. Asymptomatic persons showed high levels of interleukin-12 and interferon-gamma, whereas persons with ocular lesions had high interleukin-1 and tumor necrosis factor-alpha responses toward soluble toxoplasma tachyzoite antigen. These data suggest that patients with ocular disease due to congenital infection show tolerance toward the parasite. Furthermore, susceptibility to ocular lesions after acquired toxoplasmosis is associated with high levels of interleukin-1 and tumor necrosis factor-alpha, whereas resistance is associated with high levels of interleukin-12 and interferon-gamma.

Adolescent↗

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↗

[Toxoplasmosis and the epidemiological status of the population. II. The determination of the intensity of toxoplasmosis transmission].

The possibility of using the primary epidemiological unit, force of infection, as a criterion for evaluating the intensity of the transfer of toxoplasmosis among the population at the focus of infection has been established. The comparison of data obtained in different regions indicates that the level of the force of infection is, in general, low, but it can vary within a wide range. The problem of the suitability of using the force of infection as a criterion for dividing territories into zones with respect to toxoplasmosis is discussed.

Adolescent↗

Toxoplasmosis and pregnancy: the prevention of congenital toxoplasmosis.

Programs to prevent congenital toxoplasmosis based on the evaluation of serologic tests can be performed at three periods: 1. before pregnancy (serologic, epidemiologic screening of "at risk" women); 2. during pregnancy (detection by seroconversion); 3. at delivery (diagnosis of evident or latent congenital infection). The screening devices, the IHA, IFA, and IgM-IFA tests, should be performed first and after 3 weeks possibly repeated. During pregnancy the observation of seroconversion or, in any case, an increase in serologic titer at the second blood withdrawal and, at delivery, high serologic titers are signs of fetal risk. The significance of the data has furthermore to be evaluated by specific IgM quantification on pure serologic fractions and by in vivo isolation of Toxoplasma gondii from amniotic fluid, placenta, or the newborn CSF, blood, and/or tissue. This data may suggest the necessity of therapeutic termination of pregnancy or application of a specific chemoprophylaxis/chemotherapy.

Abortion, Habitual↗

[Toxoplasmosis round-robin test in Austria: results and limits of the toxoplasmosis screening].

In 1983 the Osterreichische Gesellschaft für Qualitätssicherung und Standardisierung medizinisch-diagnostischer Untersuchungen (OQUASTA) has invited the Department of Medical Parasitology of the Clinical Institute of Hygiene and Medical Microbiology, University of Vienna (today: Medical University of Vienna), to establish an external quality assessment service on the detection of specific antibodies against Toxoplasma gondii, one of the most prevalent protozoic parasites in the world. The objective of this project was the support of Austrian laboratories in standardising their test methods for the detection of specific antibodies against T. gondii. Between 1983 and 2004, 45 collaborating studies were carried out. During this period, the number of participating laboratories has increased from 10 in 1983 to about 50 in recent years. In total, the test results produced by the laboratories matched with the nominal values in more than 90%. On the examples of three human cases we demonstrate that externally validated serological methods alone, despite their great benefit, are not enough for a sufficient serodiagnosis of toxoplasmosis; unusually complicated serological situations do arise and can only be met by the knowledge about special tests, the application of an appropriate examination strategy and -- last but not least -- by many years of experience.

Austria↗

Levels of pyrimethamine in sera and cerebrospinal and ventricular fluids from infants treated for congenital toxoplasmosis. Toxoplasmosis Study Group.

Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography. The specimens were from 37 infants receiving pyrimethamine for treatment of suspect or proven congenital toxoplasmosis. Pyrimethamine half-life in serum was 64 +/- 12 h when determined by study of terminal-phase kinetics of samples obtained from nine babies. This half-life was significantly different (P = 0.008) from the pyrimethamine half-life (33 +/- 12 h) determined by terminal-phase kinetics for two babies of the same age taking phenobarbital. Serum pyrimethamine levels at various intervals after dosages of pyrimethamine were also lower for infants receiving phenobarbital. Levels measured in sera from babies taking the same dose of pyrimethamine throughout their first year of life did not appear to vary significantly over time or at different ages (P greater than 0.05). Mean +/- standard deviation serum levels 4 h after a pyrimethamine dose were 1.297 +/- 0.54 micrograms/ml for babies taking 1 mg of pyrimethamine per kg of body weight daily and 0.7 +/- 0.26 microgram/ml for babies taking 1 mg/kg each Monday, Wednesday, and Friday. Levels in CSF were approximately 10 to 25% of concomitant levels in serum. Serum folate levels for infants who took 0.64 to 1.7 mg leukovorin per kg ranged from 33 to 663 ng/ml. To determine whether the levels of pyrimethamine in serum and CSF of treated infants were in a range that affected the most virulent, rapidly replicating, and standard laboratory strain of Toxoplasma gondii, effects of various concentrations of pyrimethamine and sulfadiazine on replication of T. gondii in vitro were assessed. The levels of the antimicrobial agents effective in vitro were in the range of levels of pyrimethamine achieved in sera and CSF. Although folinic acid could inhibit the therapeutic effect of pyrimethamine and sulfadiazine in vitro, inhibition was noted only at levels (> or = 4,800 ng/ml) that were considerably higher than the folate levels found in the treated infants' sera.

Chromatography, High Pressure Liquid↗

Congenital toxoplasmosis. The Toxoplasmosis Study Group.

Congenital toxoplasmosis is a preventable and treatable disease with predominant neurological and ophthalmologic manifestations. These manifestations and approaches to diagnosis, treatment, and prevention of this infection are considered. Outcomes with and without treatment are emphasized. The following also are discussed: recent advances in understanding the organism; its life cycle, epidemiology, pathogenesis, and pathology; and areas in which improvements in diagnosis, treatment, and prevention are needed.

Animals↗