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PubMed2000

Protective immunity against congenital toxoplasmosis with recombinant SAG1 protein in a guinea pig model.

Primary infection with Toxoplasma gondii during pregnancy can induce fetal pathology and abortion in both humans and animals. The present study describes the development of an experimental model of congenital toxoplasmosis in the guinea pig. In this animal model, we evaluated the protective effect of vaccination with a recombinant form of SAG1 against maternofetal transmission of tachyzoites. The presence of parasites in fetuses was determined by nested PCRs and by an in vivo readout after fetal brain homogenate injections in mice. The absence of parasites was demonstrated in 66 to 86% of fetuses derived from adult guinea pigs immunized with SAG1 and challenged with the mildly virulent T. gondii strain C56. In contrast, more than 80% of fetuses from mock-immunized guinea pigs were infected. The protection was not correlated with titers of antibody to SAG1. Our results indicated that this experimental model constitutes a relevant model for evaluation of vaccine candidates against congenital toxoplasmosis and that SAG1 elicits significant protection against maternofetal transmission.

Animals↗

PubMed2006

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.

Animals↗

PubMed1975

Serological diagnosis of congenital toxoplasmosis.

A comparison of the indirect haemagglutination test (IHAT) with the dye test (DT) in 23 infants with congenital toxoplasmosis showed that in the early part of the first year of life the IHAT titres were nearly all lower than the DT titres. In six cases the IHAT was negative or the titre was so low that the cases could have been missed in routine screening. Later in the first year the IHAT titres became higher than the DT and remained so. The infants belonging to mothers with a high IHAT and therefore assumed to have become infected early in pregnancy had severe infections which included all the cases of hydrocephalus. Infants of mothers with low IHAT titres relative to the DT and therefore thought to have been infected later in pregnancy had generalized, mild or subclinical infection. With some difficulty a suitable commercial conjugated anti-IgM serum was found that gave positive results in immunofluorescent antibody tests for specific IgM antibody with all the infected infants and their mothers throughout the first year and negative results in uninfected infants and their mothers.

Age Factors↗

PubMed1978

[Clinical course of congenital toxoplasmosis in dicygotic twins (author's transl)].

The presented case report deals with the clinical course of a congenital toxoplasmosis in dicygotic twins. The variability of the clinical course was proofed, because one of the twins remained unaffected with clinical signs and was detected only by the conversion of the seroreactions. On the other hand the second twin showed the picture of an acute meningoencephalitis resulting in a neurological defect syndrome. The reasons for the different clinical course, which is more pronounced in dicygotic twins than monocygotic, remain unknown.

Diseases in Twins↗

PubMed2006

Genotyping of Toxoplasma gondii by multiplex PCR and peptide-based serological testing of samples from infants in Poland diagnosed with congenital toxoplasmosis.

Toxoplasma gondii has a clonal population genetic structure with three (I, II, and III) lineages that predominate in North America and Europe. Type II strains cause most cases of symptomatic human infections in France and the United States, although few other regions have been adequately sampled. Here we determined the parasite genotype in amniotic fluid and cerebrospinal fluid samples from congenital toxoplasmosis cases in Poland. Nineteen confirmed congenital cases of toxoplasmosis were analyzed, including both severe and asymptomatic cases. The genotype of parasite strains causing congenital infection was determined by direct PCR amplification and restriction fragment length polymorphism analysis. Nested multiplex PCR analysis was used to type four independent polymorphic markers. The sensitivity of multiplex nested PCR was >/=25 parasites/ml in amniotic fluid and cerebral spinal fluid samples. Parasite DNA was successfully amplified in 9 of 19 samples (eight severely affected and one asymptomatic fetus). Only genotype II parasites were identified as the source of T. gondii infection based on restriction fragment length polymorphism analysis. Strains causing congenital infections were also typed indirectly based on detection of antibodies to strain-specific peptides. Serotyping indicated that 12 of 15 cases tested were caused by type II strains and these positives included both symptomatic and asymptomatic infections. Overall, the combined analysis indicated that 14 of the cases were caused by type II strains. Our results are consistent with the hypothesis that parasite burden is associated with severity of congenital toxoplasmosis and indicate that serological testing provides a promising method for genotypic analysis of toxoplasmosis.

Amniotic Fluid↗

PubMed2000

Preventing congenital toxoplasmosis.

SCOPE OF THE PROBLEM: Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Acute infections in pregnant women can be transmitted to the fetus and cause severe illness (e.g., mental retardation, blindness, and epilepsy). An estimated 400-4,000 cases of congenital toxoplasmosis occur each year in the United States. Of the 750 deaths attributed to toxoplasmosis each year, 375 (50%) are believed to be caused by eating contaminated meat, making toxoplasmosis the third leading cause of foodborne deaths in this country. ETIOLOGIC FACTORS: Toxoplasma can be transmitted to humans by three principal routes: a) ingestion of raw or inadequately cooked infected meat; b) ingestion of oocysts, an environmentally resistant form of the organism that cats pass in their feces, with exposure of humans occurring through exposure to cat litter or soil (e.g., from gardening or unwashed fruits or vegetables); and c) a newly infected pregnant woman passing the infection to her unborn fetus. RECOMMENDATIONSFOR PREVENTION: Toxoplasma infection can be prevented in large part by a) cooking meat to a safe temperature (i.e., one sufficient to kill Toxoplasma); b) peeling or thoroughly washing fruits and vegetables before eating; c) cleaning cooking surfaces and utensils afterthey have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables; d) pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly; and e) not feeding raw or undercooked meat to cats and keeping cats inside to prevent acquisition of Toxoplasma by eating infected prey. RESEARCH AGENDA: Priorities for research were discussed at a national workshop sponsored by CDC in September 1998 and include a) improving estimates of the burden of toxoplasmosis, b) improving diagnostic tests to determine when a person becomes infected with Toxoplasma, and c) determining the applicability of national screening programs. CONCLUSION: Many cases of congenital toxoplasmosis can be prevented. Specific measures can be taken by women and their health-care providers to decrease the risk for infection during pregnancy and prevent severe illness in newborn infants.

Female↗

PubMed1988

Congenital toxoplasmosis in an infant with hydrops fetalis.

We have described an infant born with severe hydrops fetalis due to congenital toxoplasmosis. Although uncommon, toxoplasmosis should be considered in the differential diagnosis of hydrops fetalis, particularly when the preliminary clinical work-up suggests a nonimmunologic basis for the hydrops. Although the clinical outcome in an infant as severely affected as this one will remain poor, the therapy for toxoplasmosis has improved over the years, and with quick diagnosis of the disease, a less severely affected infant may have a better prognosis.

Animals↗

PubMed1995

[Prevention of congenital toxoplasmosis in Europe].

To sound out prevalent opinions among health authorities in Europe concerning the control and prevention of congenital toxoplasmosis (CT), a questionnaire was sent to the 28 WHO member countries in Europe. The questionnaire was returned by 23 countries. Only 7 countries recommend systematic screening of pregnant women. The reasons given by the 14 countries which do not recommend systematic screening are diverse: recommendations are in preparation, unfavourable cost-benefit return, absence of satisfactory treatment, programme not possible, incidence level too low, etc. 11 countries have a surveillance system for CT, of which only 3 are among the countries which recommend systematic screening. However, the absence of a multidisciplinary approach does not permit proper surveillance of cases. It appears from this survey that control of CT is undertaken in a very heterogeneous manner in Europe and no country has a programme whose impact on CT can be measured. So far, the European experience does not permit conclusions either in favour of or against a programme for the systematic screening of CT. However, cost-benefit analysis plays a very important role in determining whether such a programme should be implemented. Parameters such as the security of diagnosis (standardization of methods, quality and experience of the laboratories) and the monitoring of cases (definition, multidisciplinary approach to the surveillance and long-term treatment of patients, national collection of case reports, evaluation of the programme) are indispensable for the implementation of an effective surveillance system.

Cost-Benefit Analysis↗

PubMed1999

[Control of congenital toxoplasmosis in Italy: The project of the Istituto Superiore di Sanità].

Toxoplasma gondii infection during pregnancy is a public health concern; many resources are used in diagnostic and therapeutic activities, sometime with a low benefit/cost due to lack of standardization in practices. In the lack of suitable epidemiological knowledge at national level regarding the congenital toxoplasmosis trend in Italy, an evaluation of the public health impact of this pathology is required. The Istituto Superiore di Sanità (ISS) has worked out a project on a prevalence-incidence study at national level, performing standard reference methods for diagnosis and both case definition and case management. Furthermore, the ISS urges all the involved centers on congenital toxoplasmosis to set up a network for an active collaboration to this project.

Female↗

PubMed2003

Congenital toxoplasmosis: assessment of risk to newborns in confirmed and uncertain maternal infection.

UNLABELLED: We identified 205 newborns at risk of congenital infection based on their mothers' immunological status during pregnancy, using the criteria established by the European Research Network on Congenital Toxoplasmosis to define the likelihood of infection in pregnant women. Of the 205 newborns, 60 (29.2%) were born to mothers with documented seroconversion, 49 (23.9%) to mothers with probable infection, 60 (29.2%) to mothers with possible infection, and 36 (17.6%) to mothers who were unlikely to be infected. Infection was transmitted to the child in 13 out of 60 cases (21.6%) of seroconversion, in 2 out of 49 (4.1%) cases of probable infections and in none of the possible and unlikely cases. The results were further analysed considering only the 109 newborns of mothers with confirmed and probable infection; in this group, toxoplasmosis was not transmitted to any of the 45 newborns of mothers infected in the first trimester of pregnancy, whereas it was transmitted to 5 out of 29 (17.2%) cases of seroconversion and 2 out of 12 (16.6%) with probable infection in the second trimester, and to 8 out of 23 (34.8%) with confirmed infection in the third trimester (no probable infections were dated in the third trimester). Among the newborns of mothers with seroconversion, the risk of symptomatic infection was 10.4% in the second trimester and 8.7% in the third trimester. CONCLUSION: the authors have quantified the risk of transmission of toxoplasmosis infection, not only in cases of seroconversion, as reported by others, but also in infections defined as probable or possible based on presence of IgM and/or IgA and with medium-high IgG levels. Probable infections in the second trimester of pregnancy carries the same risk of transmission as seroconversions and pregnant women and their newborns in these cases should undergo the same diagnostic and therapeutic approach. It is suggested that newborns of mothers with certain and probable infection must be carefully observed and undergo clinical and serological testing to identify and treat the infection as soon as possible. In the case of possible or unlikely maternal infection, serological testing at longer intervals is nevertheless advisable without the need for treatment.

Adult↗

PubMed2001

Myelitis and ascending flaccid paralysis due to congenital toxoplasmosis.

A 4-week-old female newborn developed ascending flaccid paralysis and radiologic evidence of myelitis; the diagnosis of congenital toxoplasmosis was confirmed by the presence of Toxoplasma gondii-specific immunoglobulins in both mother and infant, and detection of Toxoplasma sequences in the infant's cerebrospinal fluid by polymerase chain reaction analysis. Treatment with pyrimethamine, sulfadiazine, and methylprednisolone resulted in improvement.

Animals↗

PubMed1988

Recognition of Toxoplasma gondii excreted and secreted antigens by human sera from acquired and congenital toxoplasmosis: identification of markers of acute and chronic infection.

While the serological response to somatic antigens of Toxoplasma gondii is currently analysed, little information is available on the antibody response to the antigens excreted and secreted by tachyzoïtes (ESA). This serological study is focused on the immune response towards these antigens which were released by the parasites in cell-free culture medium. Human sera corresponding to 'acute', 'subacute' and 'chronic' acquired infection and sera from infected newborns and from their mothers were analysed by radio-immunoprecipitation with 35S methionine-labelled ESA and with radio-iodinated membrane antigens followed by polyacrylamide gel electrophoresis. In chronic toxoplasmosis, IgG antibodies recognized among ESA major 108, 97, 86, 60, 57, 42, 39 and 28.5 kD antigens; the 108-97 kD doublets and the 28.5 kD antigen seemed characteristic of the chronic phase of toxoplasmosis. In acute infection, IgM antibodies to the 97 kD antigen, the first to appear, seem to contitute good markers of early acute infection. The comparative study of antibody response to membrane antigens showed that, in chronic toxoplasmosis, human sera recognized four antigens of 43, 35, 30 and 22 kD and that, in acute toxoplasmosis, they first recognized the 43 and 30 kD antigens. The serological evolution in congenital toxoplasmosis was the same as in acquired infection. In some cases, the serological profile of the newborn was different from that of his mother, with an additional antibody response to a 170 kD antigen. This study demonstrates in human toxoplasmosis an early, intense and characteristic antibody response against ESA, suggesting that the use of these antigens could lead in the future to improved diagnostic tests.

Acute Disease↗

PubMed1994

[Congenital toxoplasmosis, evaluation of the prevention policy].

OBJECTIVES: This study was performed to assess the effect of a prevention programme against congenital toxoplasmosis conducted as part of the French health policy developed in the Rhône department. METHODS: A descriptive epidemiological survey was conducted in 1991 including 806 post-partum women who were hospitalized in 22 maternities in the Rhône department. RESULTS: Forty-nine percent of the women had negative serology tests. French legislation requiring detecting non-immunized women at diagnosis of pregnancy was applied satisfactorily by the attending physicians. Inversely, women at risk were insufficiently informed: only 17% of the women at risk were aware of the three main routes of contamination; 63% believed vaccination is possible and 11% though they had been vaccinated. Deficient information was probably the cause of poor compliance to preventive measures as observed in this sample: only 17% of the serologically negative women stated they had applied anti-toxoplasmosis prophylaxy measures. CONCLUSION: Women at risk must be informed to convince them to modify their behaviour during pregnancy. The role of the attending physician and biologist is of major importance.

Adult↗

PubMed2003

Congenital toxoplasmosis.

Approximately 85 percent of women of childbearing age in the United States are susceptible to acute infection with the protozoan parasite Toxoplasma gondii. Transmission of T. gondii to the fetus can result in serious health problems, including mental retardation, seizures, blindness, and death. Some health problems may not become apparent until the second or third decade of life. An estimated 400 to 4,000 cases of congenital toxoplasmosis occur in the United States each year. Serologic tests are used to diagnose acute T. gondii infection in pregnant women. Because false-positive tests occur frequently, serologic diagnosis must be confirmed at a Toxoplasma reference laboratory before treatment with potentially toxic drugs is considered. In many instances, congenital toxoplasmosis can be prevented by educating pregnant women and other women of childbearing age about not ingesting raw or undercooked meat, using measures to avoid cross-contamination of other foods with raw or undercooked meat, and protecting themselves against exposure to cat litter or contaminated soil.

Animals↗

PubMed1993

Congenital toxoplasmosis: an experimental study in rhesus monkeys for transmission and prenatal diagnosis.

This paper describes a rhesus monkey model to study congenital transmission and the prenatal diagnosis of Toxoplasma gondii infection. Transmission to the fetus was investigated after maternal infection in the second (Day 90) or third trimester (Day 130) of pregnancy. A parasitemia was induced and lasted for about 10 days as proven by mouse inoculation and nested PCR on whole blood samples and peripheral blood mononuclear cells. Transmission of T. gondii was proven in 4 of 9 (44%) fetuses in the second trimester and in 3 of 9 fetuses in the third trimester of gestation. Six of the 7 proven fetal infections could be diagnosed antenatally. Postnatally, 4 additional fetuses that most likely were congenitally infected were found, although this could not formally be proven. The mothers of these 4 fetuses were infected in the third trimester. If we accept this group as being antenatally infected, an overall transmission rate is found of 11 of 18 cases (61%). This rate is similar to that found in humans. This is the first description of a monkey model for congenital toxoplasmosis, that is suitable to study the approach of antenatal diagnosis and the effectivity of treatment, with obvious relevance for Toxoplasma infections in humans.

Animals↗

PubMed1992

[Congenital toxoplasmosis in the Alpes-Maritimes region. Apropos of 26 cases observed between 1984 and 1990].

Twenty-six cases of congenital toxoplasmosis observed in the department of Alpes Maritimes (Chief Town: Nice) between 1984 and 1990 are reported. All affected children were treated by pyrimethamine and sulfonamide as soon as the diagnosis was established. None of them exhibited serious sequellae. In most cases (58%) there were no clinical manifestations in agreement with other reports. Benign manifestations were observed in 10 cases (38%): 4 chorioretinitis; 4 intracranial calcifications: 1 febrile seizure; 7 hyperproteinorachias: 3 isolated and 4 associated with other signs. In 3 cases, secondary lesions appeared during the treatment period. This confirms the need for active therapeutic research in order to decrease the risk of late ocular complication which is the major problem of the disease.

Child↗

PubMed1983

[The cerebral lesions in congenital toxoplasmosis. Study of 9 personal cases and 61 cases in the literature].

This study is a review of 70 cases of congenital toxoplasmosis; all of the patients were dead between birth and the age of nine. The anatomo-pathological examination of 9 personal cases (6 acute, 1 subacute, 2 chronic) is presented and compared with that of 61 cases from the literature. After a parasitological survey concerning the infectious agent, the author summarizes the macroscopic and the microscopic lesions of his personal cases. Those data are subsequently confronted to those referred to in the literature. The author makes an attempt to entangle the terminological confusion that exists between the different terms: cyst, pseudocyst, microglial nodule and granuloma. The frequency, the localization and the mechanisms of the main alterations - granuloma, necrosis, calcification, hydrocephaly - are studied as well as the vulnerability factors and the resistance of the subjects. The presence in 8 of the 9 chronic cases of calcified scar lesions in the inferior portion of the external wall of the lateral ventricles suggests a particular vulnerability of the spongioblasts in that area. In the acute cases the extensive necroses in the cerebral hemispheres seem to result from immunological reactions in an immature organism rather than from vascular thromboses that appear to be more a secondary phenomenon.

Acute Disease↗

PubMed2001

Neonatal screening for congenital toxoplasmosis in a cohort of 165 women infected during pregnancy and influence of in utero treatment on the results of neonatal tests.

The aim of this study was to determine the performances of methods used for the neonatal diagnosis of congenital toxoplasmosis. We included 165 pregnant women infected during pregnancy over a 10-year period. Fifty-seven cases of congenital toxoplasmosis were demonstrated (34.5%). Neonatal diagnosis gave positive results in 50 cases (88%). Parasites were isolated from placenta or cord blood in 61% of the infected newborns, more frequently from placenta (60%) than from cord blood (43%). This method was the only criterion of infection in 18% of these infected infants. The detection of specific IgM and IgA antibodies performed on 42 sera of infected infants allowed the diagnosis of congenital infection in 34 cases (81%). IgA antibodies were more frequently detected (60%) than specific IgM (50%). Neonatal and prenatal screening were carried out for 143 pregnant women. This combination diagnosed 39 of 40 infected infants (98%). Prenatal diagnosis identified 30 of 40 cases (75%). Nine cases were diagnosed through neonatal screening and one case with the postnatal follow-up. When prenatal diagnosis was positive, pyrimethamine and sulfadoxine were administered to the mothers (25 cases) in addition to spiramycin. Toxoplasma gondii was less frequently isolated in the placenta and the cord blood of these women (32% and 19%, respectively) than in women treated by spiramycin alone (83% and 63%) proving the antiparasitic action of these drugs. In conclusion, neonatal screening combining parasite detection in placenta and immunological methods on cord blood is essential particularly when prenatal diagnosis is negative. Therefore, when this diagnosis is positive, a treatment with pyrimethamine and sulfamide can be started in the first month of life.

Animals↗