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[Congenital toxoplasmosis: a new case of infection during pregnancy in an previously immunized and immunocompetent woman].

UNLABELLED: Congenital toxoplasmosis is a potentially serious infection which usually affects infants born to non immune women. CASE REPORT: Our case report focuses on a baby born to a normally immunocompetent woman previously immunized against toxoplasmosis. To our knowledge only three similar cases have been published until now. CONCLUSION: We conclude that in front of a patient neonatal congenital infection picture, toxoplasmosis cannot be excluded on the ground of maternal immunity status and must be quickly investigated, given the emergency of appropriate treatment.

Angola↗

Congenital toxoplasmosis in premature twins.

In the course of the study "Toxoplasmosis and Prematurity" 330 blood samples from twins were examined. Our findings in a series of 21 premature twins (maternal sera were also examined) are reported in this paper. Toxoplasma antibodies were detected by the Sabin-Feldman test and specific IgM antibodies by the Remington test. The classical form of congenital toxoplasmosis was present in five pairs of twins, while toxoplasmosis was subclinical at birth in both twins of three pairs. The pattern of disease varied very much in seven pairs of twins. In one twin of two pairs signs of disease were present, while his cotwin appeared unaffected but with strongly positive result of SFT. The most interesting observation, however, is that in three pairs, one twin was infected and had evident congenital toxoplasmosis, while his cotwin was not, as proven by the disappearance of the Toxoplasma antibodies. This finding undoubtedly indicates the importance of whether the placenta is intact or not for the transmission of the infection.

Antibodies↗

Congenital toxoplasmosis: to screen or not to screen?

We have reviewed the present day quantifiable cost to society of the 73 cases of congenital toxoplasmosis which are estimated to occur annually in Scotland with the cost of preventing the disease by screening and treatment. Our analysis includes advances in laboratory techniques. The cost of screening would depend on its scale and if in-house or commercial tests are used. If only 2 specimens were screened, at booking and at delivery, the screening costs are estimated to be between 0.5-0.9 times the preventable costs. If a third specimen were tested in the second trimester, to maximise scope for remedial action during pregnancy, the screening costs are 0.7-1.2 times preventable costs. As likely screening costs in most of the schemes we consider are now less than the preventable costs, a screening programme should be adopted.

Cost-Benefit Analysis↗

Prophylaxis of congenital toxoplasmosis. Effects of spiramycin on placental infection.

The results of parasitological investigation of the placenta for toxoplasma in 223 cases with documented congenital toxoplasmosis were analysed according to whether the mother had been treated, or not, with spiramycin during pregnancy. The investigation was negative in 10-11% of the cases when the mother had not been treated or had been inadequately treated; in 25% of the cases with a treatment of 3 g spiramycin day; and in 50% with spiramycin plus the combination of pyrimethamine with sulphonamide. This series is compared with a previous group of 321 women whose placental investigation was negative in 50% of untreated cases and 81% of treated women. The treatment categories are not directly comparable, because it is not possible to have a randomly assigned 'no treatment' group, for ethical reasons. Correlation between spiramycin treatment and negative results of mouse inoculation of placental material suggests that spiramycin might decrease the risk of materno-fetal transmission of toxoplasma by reducing the severity and duration of toxoplasmic placentitis. Current use of spiramycin in infected pregnant women is recommended because of its activity and lack of side effects. The dosage must not be lower than 3 g/day. Additional pyrimethamine plus sulphonamide should be restricted to selected cases with fetal abnormality diagnosed during pregnancy. Some data on pharmacology of spiramycin in mothers, placentas and fetuses are reviewed. They suggest that monitoring of maternal serum antibody titres for a dosage more adapted to individual cases may be desirable.

Female↗

Congenital toxoplasmosis: epidemiologic features and control.

Toxoplasmosis is caused by the parasite Toxoplasma gondii. It is acquired from undercooked meat or from food or fomites contaminated by cat feces. The disease can be transmitted to the fetus only during maternal parasitemia, which is associated with primary infection. Extrapolation from current data suggests that there are 140 to 1400 cases of congenital toxoplasmosis per year in Canada and that 70 to 280 of the infants are severely affected at birth; many of the others suffer sequelae later in life. Serologic diagnosis of primary infection in the mother is quite sensitive and specific. Diagnosis in the infant is more difficult and may take several months. Prenatal treatment of the woman and postnatal treatment of the infant are hampered by the lack of proven efficacy as well as ethical and compliance problems. Preventive serologic screening and prophylaxis have the same drawbacks. Educating young women to avoid infection is an inexpensive, low-risk intervention that would be the preferred preventive strategy if it could be shown to be effective. Immunization may prove to be the most cost-effective method of preventing congenital toxoplasmosis if a safe and effective vaccine is developed.

Abortion, Therapeutic↗

Vaccination with Toxoplasma gondii SAG-1 protein is protective against congenital toxoplasmosis in BALB/c mice but not in CBA/J mice.

We evaluated the effect of vaccination with the SAG1 protein of Toxoplasma gondii against congenital toxoplasmosis in mice with different genetic backgrounds. In BALB/c mice (H-2(d)), vaccination reduced the number of infected fetuses by 50% and was associated with a mixed type 1 and type 2 immunity. In CBA/J mice (H-2(k)), vaccination increased the number of infected fetuses by 50% and was associated with a predominant type 2 response. Our results indicate that the effect of vaccination with SAG1 is controlled by the genetic background of the mouse.

Animals↗

Clinical value of specific immunoglobulin E detection by enzyme-linked immunosorbent assay in cases of acquired and congenital toxoplasmosis.

The clinical value of immunoenzymatic (enzyme-linked immunosorbent assay) detection of anti-Toxoplasma immunoglobulin E (IgE) was assessed by studying 2,036 sera from 792 subjects, comprising seronegative controls and subjects with acute, active, reactivated, or congenital toxoplasmosis. Included were nonimmunized adults; pregnant women with recently acquired infection (acute toxoplasmosis); immunocompetent subjects with recently acquired severe infection (active toxoplasmosis) expressed as fever, adenopathies, splenomegaly, pneumonia, meningitis, or disseminated infection; subjects-some of them immunocompromised-whose previously moderate IgG antibody levels rose, suggesting a reactivation of quiescent toxoplasmosis; and infants born to seroconverted mothers and evaluated for diagnosis of congenital infection and therapeutic management. Specific IgE antibodies were never detected in seronegative subjects. They were present in 85.7% of asymptomatic seroconverters and in 100% of seroconverters with overt toxoplasmosis, following two different kinetics: in the former, the specific IgE titer generally presented a brief peak 2 to 3 months postinfection and then fell rapidly, whereas specific IgE persisted at a very high titer for several months in the latter. IgE emerged concomitantly with the increase in IgG during toxoplasmic reactivation. For neonatal diagnosis of congenital toxoplasmosis, IgE was less informative than IgM and IgA (sensitivities, 59.5, 64.3, and 76.2%, respectively) and had a specificity of 91.9%. Nevertheless, simultaneous measurement of the three isotypes at birth improved the diagnostic yield to 81% relative to the combination of IgA and IgM. Emergence of specific IgE during postnatal treatment for congenital toxoplasmosis is a sign of poor adherence or inadequate dosing.

Acute Disease↗

Classification system and case definitions of Toxoplasma gondii infection in immunocompetent pregnant women and their congenitally infected offspring. European Research Network on Congenital Toxoplasmosis.

Classification systems and case definitions provide the foundations upon which clinical and epidemiological studies are based. The European Research Network on Congenital Toxoplasmosis acknowledged the lack of such a system or definitions within its field of interest and established a working group to address the issue. Congenital Toxoplasma gondii infection was defined as occurring in four separate patient groups: pregnant women, fetuses, infants, and individuals > 1 year of age. The likelihood of Toxoplasma gondii infection was separated into five mutually exclusive categories: definite, probable, possible, unlikely, and not infected. Inclusion within a specific category is dependent upon the case definition, which is in turn derived from criteria based on serological, parasitological, and clinical information. Notes are included within the classification not only to clarify the definitions, but also to improve the reliability and quality of diagnosis. The goal is to construct a system that encompasses all aspects of congenital toxoplasmosis, which is applicable to different countries and health services, suitable for large epidemiological studies, aids the diagnosis and management of individual cases, and lends itself to computerisation.

Female↗

[Value of prevention of congenital toxoplasmosis].

PURPOSE: To verify incidence of toxoplasmosis seroconversion during pregnancy and the interest of treating the mother. METHODS: Among 7044 infants born between January 1989 and December 1993, 78 (1.1%) born to mothers who developped toxoplasmosis seroconversion during pregnancy were followed. RESULTS: Among 69 mothers treated, there were only 9 cases of congenital toxoplasmosis (13.4%) including only 3 cases of patent toxoplasmosis. CONCLUSION: Treating the mother is an effective means of preventing toxoplasmosis. The cost of verifying seronegativity in women during pregnancy could be reduced by primary prevention.

Coccidiostats↗

Rat model of congenital toxoplasmosis: rate of transmission of three Toxoplasma gondii strains to fetuses and protective effect of a chronic infection.

The incidence of congenital toxoplasmosis in Fischer rats infected between the 8th and 12th days of pregnancy with three different strains of Toxoplasma gondii (RH, 76K, and Prugniaud) were 58.2, 35.2, and 62.8%, respectively. No infected fetuses were collected from rats previously infected with RH or Prugniaud strain parasites, even if the rats were reinfected during pregnancy. Since pups from chronically infected mothers are protected from congenital toxoplasmosis, rat infection could thus constitute a relevant model for immunological studies and vaccine design.

Animals↗

Ecological comparison of the risks of mother-to-child transmission and clinical manifestations of congenital toxoplasmosis according to prenatal treatment protocol.

We compared the relative risks of mother-to-child transmission of Toxoplasma gondii and clinical manifestations due to congenital toxoplasmosis associated with intensive prenatal treatment in Lyon and Austria, short term treatment in 51% of Dutch women, and no treatment in Danish women. For each cohort, relative risks were standardized for gestation at seroconversion. In total, 856 mother-child pairs were studied: 549 in Lyon, 133 in Austria, 123 in Denmark and 51 in The Netherlands. The relative risk for mother-to-child transmission compared to Lyon was 1.24 (95% CI: 0.88, 1.59) in Austria; 0.59 (0.41, 0.81) in Denmark; and 0.65 (0.37, 1.01) in The Netherlands. Relative risks for clinical manifestations compared with Lyon (adjusted for follow-up to age 3 years) were: Austria 0.19 (0.04, 0.51); Denmark 0.60 (0.13, 1.08); and The Netherlands 1.46 (0.51, 2.72). There was no clear evidence that the risk of transmission or of clinical manifestations was lowest in centres with the most intensive prenatal treatment.

Anti-Bacterial Agents↗

[Cerebral CT scan alterations in children with ocular lesions caused by congenital toxoplasmosis]

OBJECTIVE: To evaluate the frequency and the types of cerebral CT scan alterations in patients with ocular lesions caused by congenital toxoplasmosis. METHODS: The patients should fit one of the following criteria: reagent IgM serology for toxoplasmosis at birth and mother with positive serology for toxoplasmosis; age less than ten years, with bilateral funduscopic lesions compatible with toxoplasmic retinochoroiditis; or reagent IgG serology for toxoplasmosis and mother with positive serology for toxoplasmosis. All patients were submitted to noncontrast cerebral CT scan. RESULTS: Twenty-two patients participated in this study (44 eyes). Thirteen eyes presented macular lesions (29.5%), eight had peripheral lesions (18.2%) and 22 eyes had concomitant macular and peripheral lesions (50%). Seventeen patients presented radiological alterations (77.3%). Among these, sixteen patients (94.1%) presented brain calcifications, two patients (11.7%) presented ventricular dilation, two patients (11.7%) had hydrocephalus, one had hydranencephaly (5.9%), one presented porencephalic cyst (cerebral hemiatrophy) (5.9%), one had arachnoid cyst (5.9%) and one had mild dilation of ventricles and subarachnoid cistern (5.9%). CONCLUSIONS: Patients diagnosed with congenital toxoplasmosis and ocular lesions should be investigated for concomitant neuroradiologic alterations.

Journal Article↗

Simultaneous determination of pyrimethamine, sulfadiazine and N-acetyl-sulfadiazine in plasma for monitoring infants in treatment of congenital toxoplasmosis.

A method for the simultaneous determination of pyrimethamine, sulfadiazine and its metabolite N-acetyl-sulfadiazine in small plasma samples from neonates in treatment for congenital toxoplasmosis has been developed. In this method only 25 microl of plasma is used and a simple sample preparation based on protein precipitation and centrifugation provides highly reliable data as the recovery is about 100% and the precision is good. The analysis is performed using high performance liquid chromatography with UV and mass spectrometric (MS) detection. Pyrimethamine was found to give a linear response using MS detection in the range 0.02-5 microg/ml. Sulfadiazine and its metabolite N-acetyl-sulfadiazine were preferably analysed by UV at 269 nm in the concentration ranges 0.2-200 microg/ml for sulfadiazine and 0.2-50 microg/ml for N-acetyl-sulfadiazine.

Chromatography, High Pressure Liquid↗

[Congenital toxoplasmosis in two newborn infants (author's transl)].

Two newborn infants with congenital toxoplasmosis despite serological testing during pregnancy were observed at our premature and neonatal intensive care unit within a short time of one another. In one case the counter-regulatory late first test, performed only in the 26th week, was positive with a high titre. The immediately recommended treatment was not carried out. Apart from the signs of congenital generalized infection, the newborn infant already manifested chorioretinitis and encephalitis. In the second case the initially serologically-negative pregnant women became infected only during the 35th to 36th week of gestation, around the time of the third serological examination. The child was born with slight signs of general infection, but without CNS involvement. Immediate postnatal treatment resulted in complete cure. This shows that such rare cases which can no longer be detected by serological testing can be treated postnatally with good results.

Adult↗

[Identification of risk factors for infection with Toxoplasma gondii in Serbia as a basis of a program for prevention of congenital toxoplasmosis].

BACKGROUND: Toxoplasmosis has long been known as a major cause of perinatal morbidity. Acute infection in pregnancy may lead to fetal infection and subsequent fetal loss or birth of a manifestly or latently infected infant. However, it is a preventable disease. In Europe, significant variations have been shown to occur not only between countries but also within a given country indicating local variations in the influence of epidemiological factors contributing to infection. Thus, many European countries have implemented prevention programs in measure with the respective estimated risk of congenital toxoplasmosis. Since in view of its cost, a general screening-in-pregnancy program is at present not an option in Serbia & Montenegro, insight into the risk factors of particular local significance may therefore improve the quality of and the compliance with the hygienic and dietetic advice given to pregnant women as a preventive measure, as well as identify the particular subpopulations at an increased risk of infection, who may then be selectively screened. SUBJECTS AND METHODS: A retrospective study of risk factors for Toxoplasma gondii infection based on serological and epidemiological data (questionnaire) was performed in a series of 2936 women aged 15-49 years from throughout Serbia tested in our laboratory between 1988 and 1997. Inclusion criteria included availability of serological and epidemiological data (as specified below). Specific anti-Toxoplasma antibodies were detected by the reference Sabin-Feldman dye test as modified by Desmonts into the lysis test. The questionnaire included questions on age (stratified into five-year groups), degree of education (modalities: grade school, secondary or university level), and community of residence (urban/suburban), as well as on life-style habits pertaining to infection transmission risk factors: consumption of undercooked meat, exposure to soil, and exposure to cats (pet cat ownership). In addition, the year of entry into the study was taken as a variable per se. STATISTICS: The difference in the rates of infection between groups was evaluated by the chi-square test (chi 2). Logistic regression (univariant and multivariant approaches) was used to analyze the association between Toxoplasma infection and the specific demographic and epidemiological factors. RESULTS: The overall prevalence of infection was 69%, but with very wide variations both over time (decreasing from 86% in 1988 to 39% in 1997) and region (40-90%). The risk of infection increased from the south to the north (RR = 0.97, CI = 0.94-0.98). Within Belgrade, the risk was higher in urban than in suburban zones (RR = 0.79, CI = 0.64-0.93). The single infection transmission factor that was shown to be a predictor of infection in the whole study group was undercooked meat consumption (RR = 1.6, CI = 1.2-2.1), while exposure to soil was a predictor only in women aged 15-19 (RR = 10.3, CI = 2.7-38.6). Owing pet cats had no influence. While T. gondii infection was not associated with pathological pregnancies (p = 0.51) in the whole study population, it was significantly associated with pathological pregnancies in women exposed to both undercooked meat consumption (p = 0.009) and in those aged 15-19 in contact with soil (p = 0.022), as well as in women residing in highly urban communities (p = 0.048). CONCLUSION: The dramatic decrease in the prevalence of T. gondii infection over the nineties resulted in a rising proportion of women exposed to infection in pregnancy and consequently in an increased risk of congenital toxoplasmosis. Since the financial status of the country's health system does not allow for a general screening-in-pregnancy program, we propose, based on the above data, health education of all pregnant women in combination with serological testing of those exposed to predictors of infection as an epidemiologically sound and financially sustainable alternative.

Adolescent↗

Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine.

The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or IgA-antibodies on 3 mm blood spots collected from phenylketonuria [PKU cards (Guthrie cards)]. Toxoplasma-infected children received 3 months' continuous treatment with 50-100 mg/kg per day sulfadiazine in two separate administrations and 1 mg/kg per day pyrimethamine after a 1-day loading dose of 2 mg/kg, and folinic acid 7.5 mg was administered twice weekly. Blood cell counts and body weight were recorded during follow-up. The plasma concentrations of pyrimethamine and sulfadiazine were analysed in a subgroup of seven children, using high performance liquid chromatography with ultraviolet and mass spectrometric detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5x10(9)/l, and one infant had an elevated bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was <or=0.5x10(9)/l or lower in 4/29 (13.8%). None of the children had anaemia or thrombocytopenia. The drugs did not affect weight gain. Mean plasma drug concentrations varied between 1.3 microg/ml and 2.2 microg/ml for pyrimethamine and between 60 microg/ml and 86 microg/ml for sulfadiazine. Treatment efficacy is still a concern, since progression of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their weight gain. Drugs given in the recommended doses led to concentrations within expected therapeutic limits.

Antiprotozoal Agents↗