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A maternal screening program for congenital toxoplasmosis in Quindio, Colombia and application of mathematical models to estimate incidences using age-stratified data.

We studied 937 pregnant women from Quindio, Colombia for the presence of specific anti-Toxoplasma gondii IgG antibodies using the indirect immunofluorescence antibody technique (IFAT-IgG). Specific anti-T. gondii IgM antibodies detected using the immunosorbent agglutination assay (ISAgA-IgM) were investigated in patients with high titers in the IFAT-IgG (dilutions > or = 1:1,024). We used mathematical models based on the age prevalence results of the IFAT-IgG to estimate the number of seroconversions and these were compared with the results predicted by the IgM based-incidence results. We found 15 positive cases by ISAgA-IgM and we were able to follow the children of six mothers from this group in which we found one case of congenital toxoplasmosis with the development of a retinal scar despite prenatal and postnatal treatment. The estimation of new cases for the annual total of pregnancies (approximately 8,000) in the Quindio region was 30-120 according to the ISAgA-IgM results and 57-85 using mathematical models. Thus, mathematical models based on age prevalence can give useful estimations of the magnitude of the problem.

Adolescent↗

Studies on a murine model of congenital toxoplasmosis: vertical disease transmission only occurs in BALB/c mice infected for the first time during pregnancy.

The incidence of congenital toxoplasmosis was determined by an ELISA in the litters of BALB/c mice which had been infected 8 weeks before mating, on day 12 of pregnancy, or on both these occasions. Of those mice given the infection for the first time on day 12 of pregnancy, 5 out of 6 gave birth to infected litters with approximately 50% of the individuals in each litter being infected. BALB/c mice which had been infected 8 weeks before mating did not give birth to infected litters, even if they were reinfected on day 12 of pregnancy. Following infection BALB/c mice were found to harbour significantly fewer tissue cysts than the congenic H-2 derivative BALB/K strain. However, chronically infected BALB/K mice also failed to produce infected litters, indicating that tissue cyst burden in the dam did not influence congenital infection at least on the BALB background. This study demonstrates that BALB/c dams chronically infected with Toxoplasma gondii, have immunity capable of protecting their embryos from congenital infection, even if the dams are reinfected during pregnancy. Our results demonstrate that the BALB/c mouse can be used as a model of human or ovine congenital T. gondii infection suitable for testing putative vaccines.

Animals↗

Congenital toxoplasmosis: diagnosis by exfoliative cytology.

Toxoplasmosis, caused by the intracellular protozoan Toxoplasma gondii, has as its major routes of acquisition either ingestion (of the cyst or oocyte) or transplacental infection (by trophozoites). Transplacental transmission occurs to the fetus in utero or to the newborn at vaginal delivery. Maternally acquired infections can infect the embryo as early as the 7th week of gestation. It has been estimated that 15-17% of maternal infections acquired between the 7th and 14th weeks of gestation are transmitted to the embryo (Lynfield R, Eaton RB., Teratology 1995;52:176-180.). We present a 7-wk-old white male, delivered at 38 wk of gestation, who shortly after birth was found to have hepatosplenomegaly and anemia; he developed liver failure and ascites with persistent anemia during the first week of life. After an extensive, but nondiagnostic, work-up, a paracentesis was performed which led to a diagnosis of congenital toxoplasmosis. This case demonstrates the utility of exfoliative cytology in determining the cause of neonatal ascites, especially of an infectious etiology. To our knowledge, this represents the first reported case of Toxoplasma gondii diagnosed by exfoliative cytology in a pediatric patient.

Anemia↗

Effect of Toxoplasma gondii infection kinetics on trophoblast cell population in Calomys callosus, a model of congenital toxoplasmosis.

This work evaluated the kinetics of events that occur in the placenta of Calomys callosus after Toxoplasma gondii infection. Animals on the first day of pregnancy (dop) and virgin nonpregnant females were perorally infected with 20 cysts of T. gondii strain ME49. After 100 days of infection, the virgin animals were mated and received an additional 20 cysts on the first dop. The placentas and the embryos from both acutely and chronically infected animals were analyzed up to day 20 of pregnancy by morphological and immunocytochemical assays. Noninfected and infected animals exhibited placenta with normal morphology. From the seventh dop and infection onwards, liver and spleen cells of the infected animals contained several parasitophorous vacuoles. On the 13th day, the maternal blood present at the placental blood spaces contained T. gondii-infected leukocytes. Infected placental cells were only seen on the 15th dop, being the trophoblast giant cells, the first cell type to contain signs of the parasite internalization, followed by labyrinth zone cells 24 h later and spongiotrophoblast cells only after the 19th dop. Fetal liver and brain were infected by T. gondii concomitantly to the labyrinth cell infection. No signals of infection were observed on placentas and embryos from chronically infected animals. Therefore, considering the sequence of events leading to the infection of the various organs, it could be hypothesized that the placenta is infected later on during pregnancy, which may be related to the defense roles played by this structure. However, trophoblast giant cells are unable to completely stop the progression of T. gondii infection towards the fetal tissues. C. callosus was demonstrated to be a suitable experimental model to study the dynamics of congenital toxoplasmosis.

Animals↗

Congenital toxoplasmosis in twins: a report of fourteen consecutive cases and a comparison with published data.

BACKGROUND: The combined influence of congenital toxoplasmosis and twin pregnancy on the duration of gestation has not been previously examined. Similarly little is known about the influence of genetic factors on the clinical course of this disease. The present study addresses these issues. PATIENTS AND METHODS: Fourteen consecutive twin pairs born of mothers with Toxoplasma seroconversion during pregnancy were monitored after birth and during childhood, and the relevant data were compared with those already documented for similar cases. RESULTS: The presumed time of gestation at which women became infected was earlier in noninfected than in infected twins (P = 0.007). Congenital infection did not influence the duration of pregnancy either in our own cases [36.2 +/- 4.3 weeks for noninfected children and 37.4 +/- 1.8 weeks for infected ones (P = 0.45)] or in previously published ones [35.4 +/- 3.6 weeks (P = 0.69)]. The infection status was identical for monozygotic twins (with one exception) but different for dizygotic ones (19 of 20 vs.35 of 45 cases). The clinical course through childhood corresponded more closely for monozygotic twins than for dizygotic ones [17 of 20 vs.20 of 45 cases (P = 0.007)]. CONCLUSION: Twin pregnancy is not a risk factor either for premature birth or for Toxoplasma infection in contaminated twins. The closely corresponding infection status between monozygotic twins highlights the crucial role played by the placenta in disease transmission. However, the substantial proportion of discrepant clinical courses suggests that other, as yet unknown, factors may be involved.

Adult↗

Congenital toxoplasmosis: a prospective survey in Brussels.

A prospective survey of antenatal patients was made at a hospital in Brussels over the period 1979-1982 to assess the incidence of congenital toxoplasmosis. Of 2986 patients assessed, 1403 (47%) had no toxoplasma antibodies and were at risk. The susceptible population was assessed every 6 weeks and 20 of these women (1.4%) seroconverted during pregnancy. Ten of the seroconverters had a therapeutic abortion; of the remaining 10 two gave birth to congenitally infected infants. Of the 1583 (53%) patients with a positive serology for toxoplasmosis initially, 17 (1.1%) had high antibody titres indicating that the infection could have taken place early in pregnancy. Nine infants born to these women were followed at our hospital and two of them were affected.

Adult↗

[Congenital toxoplasmosis: pediatric approach. Consensus report of the Swiss infectious disease pediatricians].

The first part of this paper reviews: (1) the spectrum of clinical features of congenital toxoplasmosis; (2) the natural course of fetal infection; (3) the influence of antitoxoplasma therapy on the course of the disease; (4) methods for diagnosing the toxoplasma infection and assessing the severity of the disease; (5) currently used antitoxoplasma drugs and different therapeutic regimens. The second part suggests a practical approach to the problem of congenital toxoplasma infection, including diagnostic work-up, drug therapy, and follow-up. This practical approach is modulated according to the clinical syndrome in the infant and diagnostic and therapeutic considerations in the mother.

Coccidiostats↗

[Congenital toxoplasmosis: presentation of a case].

We report a case of a 4 months old boy with esotropia of the left eye with large bilateral chorioretinal toxoplasmic macular scars. Chorioretinal scars are the most common eye finding in congenital toxoplasmosis and are often located in the macular region. Most infants with congenital infection are asymptomatic at birth but will develop retinal and/or neurologic damage later in life with consequent loss of vision. A routine examination of the fundus and computed tomography of the head can be negative. Serologic testing is essential for the diagnosis and the follow-up of the infection. Every infant with evident or suspected congenital infection by Toxoplasma gondii must be treated by Pyrimethamine, Sulphadiazine and Folinic Acid during at least the first year of life with regular serologic testing and ophthalmologic examination. Neurologic outcome is better with treatment and the risk of chorioretinitis seems reduced.

Child, Preschool↗

Host-parasite relationship in the brains of mice with congenital toxoplasmosis.

The wall of intact tissue cysts in the brains of mice with congenital toxoplasmosis was investigated using light and electron microscopy. Impregnation of the wall with reduced silver salts and protargol silver suggested that it was composed, at least in part, of components derived from the neuronal cytoskeleton. Electron microscopy extended these observations and revealed that intact cysts were separated from the extracellular compartment by a layer of neurofibrillae enclosed within the host cell membrane. It is suggested that this may be a means whereby intact Toxoplasma tissue cysts are protected from the host's immune response.

Animals↗

Diagnosis of congenital toxoplasmosis by two-dimensional immunoblot differentiation of mother and child immunoglobulin g profiles.

Differentiation between the specific immunoglobulin G (IgG) response to Toxoplasma gondii by a mother and her newborn child is helpful in the diagnosis of congenital infection with T. gondii in newborns without T. gondii-specific IgM and/or IgA antibodies at birth. Previous methods include immunoblotting and complexing T. gondii antigen with the sera from the mother and child and comparing the bands after electrophoresis. We developed a two-dimensional immunoblotting (2DIB) method with T. gondii RH strain tachyzoite antigen and validated the method with sera from 11 children identified through the neonatal screening program for congenital toxoplasmosis in Denmark. The children were identified by using Toxoplasma-specific IgM antibodies at the screening test, but the presence of T. gondii-specific IgM and/or IgA antibodies could not be confirmed at the subsequent serum sample tested. The children were monitored for at least 12 months, and in seven of eight patients monitored for 12 months the results of the 2DIB-predicted congenital infection were confirmed by the presence of persistent Toxoplasma-specific IgG antibodies. 2DIB is a sensitive technique that allows early differentiation between passively transferred maternal T. gondii-specific IgG antibodies and antibodies synthesized by the newborn child.

Animals↗

Toxopain-1 is critical for infection in a novel chicken embryo model of congenital toxoplasmosis.

We tested the hypothesis that cathepsins and specifically toxopain-1, a cathepsin B, play a critical role in the pathogenesis of toxoplasmosis. We found that inhibiting the expression of toxopain-1-specific mRNA and protein by >60% significantly decreased the capacity of the parasites to multiply and invade in vitro. To relate these in vitro results to the role of toxopain-1 in pathogenesis in vivo, we developed a novel chicken embryo model of congenital toxoplasmosis. Inhibiting either toxopain-1 expression or specific cysteine proteinase activity significantly reduced congenital infection of chicken embryos, as determined by histopathology and by the number of parasites quantified by real-time PCR. Our new model provides key in vivo validation for the hypothesis that toxopain-1 is a potential drug target in Toxoplasma gondii and also provides a new animal model for rapid, inexpensive screening of antiparasitic compounds.

Animals↗

Late cerebral relapse of congenital toxoplasmosis.

Focal encephalitis occurred in a girl with activation of chorioretinitis which on clinical and serological grounds was taken to be caused by toxoplasma. The encephalitis and acute ocular inflammation resolved with treatment with pyrimethamine and sulphadiazine. This is presumably an example of reactivation of congenital cerebral toxoplasmosis.

Child↗

Detection of specific immunoglobulin E during maternal, fetal, and congenital toxoplasmosis.

Toxoplasma immunoglobulin E (IgE) antibodies in 664 serum samples were evaluated by using an immunocapture method with a suspension of tachyzoites prepared in the laboratory in order to evaluate its usefulness in the diagnosis of acute Toxoplasma gondii infection during pregnancy, congenital infection, and progressive toxoplasmosis. IgE antibodies were never detected in sera from seronegative women, from patients with chronic toxoplasma infection, or from infants without congenital toxoplasmosis. In contrast, they were detected in 86.6% of patients with toxoplasmic seroconversion, and compared with IgA and IgM, the short kinetics of IgE was useful to date the infection precisely. For the diagnosis of congenital toxoplasmosis, specific IgE detected was less frequently than IgM or IgA (25 versus 67.3%), but its detection during follow-up of children may be interesting, reflecting an immunological rebound. Finally, IgE was detected early and persisted longer in progressive toxoplasmosis with cervical adenopathies, so it was also a good marker of the evolution of toxoplasma infection.

Adolescent↗