The burden of congenital toxoplasmosis in Europe has recently been reviewed (Be´nard and Salmi, 2006a). The lowest incidence of maternal infection was observed in the northern European countries (from 0.13% in Norway to 0.5% in Sweden), and the highest incidence was reported from France of 1.5% and 1.6% (Ancelle and Goulet, 1996; Jeannel et al., 1988), 1.4 and 2.6% in Belgium (Foulon et al., 1984), and 3.5% in Italy (Ricci et al., 2003). Low levels of toxoplasma-specific IgM antibodies may be found for several years after acute infection, and the mere demonstration of low levels of toxoplasma-specific IgM antibodies is therefore not regarded as a sign by itself of acute infection with T. gondii (Liesenfeld et al., 1997, 2001a,b; Robert et al., 2001; Gras et al., 2004; Leroy et al., 2006).
Maternal–Fetal Transmission Of T. Gondii
The risk of maternal–fetal transmission by trimester of pregnancy is dependent on gestational age and increases throughout pregnancy (Desmonts et al., 1965; Dunn et al., 1999; Gilbert et al., 2001, 2003; Thie´baut et al., 2006c).
Prevalence Of Congenital Toxoplasmosis At Birth
The prevalence of toxoplasmosis at birth varied from 0.7 per 10 000 births in Sweden (Fahnenhjelm et al., 2000; Evengard et al., 2001) and 2 per 10 000 births in Denmark (Lebech et al., 1999) to 7 per 10 000 births in the Poznan region, Poland (Paul et al., 2001).
The risk of pediatric complications varied according to complication types. The three complications that were the most frequently reported were retinochorioditis followed by intracranial calcifications and hydrocephalus. The prevalence of intracranial calcifications at birth varied from 6.3 to 10.6%, and the prevalence of hydrocephalus from 0 to 1.8%.
In the largest study with long-term follow-up the observed prevalence of eye lesions was 12.6% during infancy, increasing to 35% at 12 years (Binquet et al., 2003). Bilateral, visual impairment was extremely rare (Binquet et al., 2004).
The European Multicenter Study on Congenital Toxoplasmosis (EMSCOT) cohort has found that approximately 5% of infected children had neurological impairment or die due to congenital toxoplasmosis (Thie´baut et al., 2006c).
European Screening Programs For Congenital Toxoplasmosis
The national public health programs and recommendations to prevent toxoplasmosis that have been developed in Europe involve three kinds of control measures:
- Prenatal screening to detect as early as possible maternal toxoplasma infections (or suspicion of such infections) that might indicate a risk for congenital infection leading to a prenatal treatment.
- Newborn screening to detect infections as early as possible to enable early initiation of infected infants.
- Primary prevention programs to educate pregnant women on how to avoid infection (no official or national programs).
The different approaches to surveying congenital toxoplasmosis in Europe have been recently reviewed (Be´nard and Salmi, 2006b).
Prenatal Screening
Austria introduced a mandatory serological screening of pregnant women for toxoplasmosis in 1975 (Aspo¨ ck and Pollak, 1992; Aspo¨ ck, 2000, 2003). Every pregnant woman is tested for antibodies at the first antenatal clinical attendance. The test is repeated at no greater than 2-month intervals in the second and third trimester of pregnancy in seronegative women. In case of a low titer at the first visit, another test is carried out 3 weeks later and usually confirms an old infection (Aspo¨ ck, 2000). If a primary T. gondii infection of the pregnant woman is suspected because of seroconversion or significant rise of IgG titer (or primary high titer with IgM), prenatal treatment is carried out as soon as possible with spiramycin before the 16th week of gestation and pyrimethamin plus sulfadiazine after the 15th week of gestation. This program is subsidized and thus free of charge. Use of financial incentives guarantees an almost 100% testing of pregnant women, as a part of the ‘Mutter-Kind-Pass’ (mother-child-passport, or MKP); between 1975 and 1997, every woman who had all examinations received a sum of 1090€. However, in 1997, only women with a low income received an incentive (145€), and although the examinations remained free of charge, about 10% of women went untested. In 2002, a new regulation was introduced, ‘Kinderbetreuunsgeld,’ in which a daily sum of 15€ is provided from birth to the child’s third birthday, provided that all tests of the MKP have been performed. This measure resulted in an almost 100% participation in the screening program.
In France testing has been mandatory since 1978 and, since 1985, to screen toxoplasma infection during pregnacy. Premarital examinations are conducted to distinguish previously infected women from women who have not been previously infected. When a previously nonimmune woman or a woman with an unknown serological status becomes pregnant, testing is conducted at her first prenatal examination during the first trimester and at six additional examinations conducted monthly during her second and third trimesters, then testing is performed on cord blood at delivery. In addition, since 1983 a leaflet describing hygienic measures is given along with the laboratory results. The French program is free of charge.
There are no national guidelines on the management of seroconversions (Binquet et al., 2004), and actual practice varies from center to center.
In utero diagnosis is performed through amniocentesis using detection of T. gondii-specific nucleic acid (PCR) on amniotic fluid and ultrasound examinations of the fetus. If fetal infection is confirmed, pregnancy termination is offered. If the pregnancy is continued, treatment is changed to pyrimethamine and sulfadiazine or sulfadoxine with folinic acid. Newborns are tested to ensure early diagnosis and treatment of asymptomatic congenital toxoplasmosis with the goal of preventing later reactivation and late complications, especially ocular.
In practice, there is great variability between the specialized centers in France with regard to the indications for therapeutic abortion and amniocentesis, treatment protocols with pyrimethamine and sulfonamides, as well as in the frequency of sonographical monitoring (Binquet et al., 2004). Toxoplasma infection is not notifiable in France.
In Slovenia, there are national recommendations to educate pregnant women about preventing congenital toxoplasmosis, using leaflets and information during the first prenatal visit. Pregnant women are tested at the beginning of pregnancy and, in case of seronegativity, retested in the second and third trimesters of pregnancy (at 20–24 and 32–36 weeks, respectively) (Logar et al., 2002). Only a single review addresses the anxiety that systematic screening induces in pregnant women (Khoshnood et al., 2006).
Neonatal Screening
Neonatal screening for congenital toxoplasmosis is performed in New England in the United States, Denmark, and parts of South America (e.g., parts of Brazil and Colombia), by analyzing the blood samples obtained on filter paper with tests for specific IgM antibodies (Guthrie cards) day 5 postpartum (Guerina et al., 1994; Lebech et al., 1999; Sørensen et al., 2002; Neto et al., 2004). However, 15 to 55% of congenitally infected children do not have detectable toxoplasma-specific IgM antibodies at birth or early infancy (Decoster et al., 1992; Lebech et al., 1999; Leroy et al., 2006).
No Screening Policies
Currently, 21 European countries do not recommend screening for congenital toxoplasmosis. Eighteen countries officially recommend a primary prevention program alone, without any screening. These primary prevention programs are carried out at the first antenatal visit, instructions are given on how to avoid eating raw or undercooked meat, to avoid cross-contamination of other foods with raw or undercooked meat, and to use cat litter and practice soil-related hygienic measures. The rationale given by these countries for not recommending screening is diverse: unfavorable cost–benefit return, absence of satisfactory treatment (to be discussed later), program not feasible or too expensive, or incidence of toxoplasmosis infection too low (Janitschke 2003; Joynson 2003; Lappalainen 2003; Stray-Pedersen 2003; Be´nard and Salmi, 2006b).