Background of congenital toxoplasmosis

After the ingestion of food or water contaminated with T. gondii, there is parasitemia, and tachyzoites can invade the placenta if the woman is pregnant. Humans have haemochorial placenta. Nearly half of fetuses whose mothers become infected during pregnancy escape T. gondii infection. The global rate of transmission during pregnancy is 29% (Dunn et al., Reference Dunn, Wallon, Peyron, Petersen, Peckham and Gilbert1999). The stage of gestation at the time of mother's infection may determine the transmission of T. gondii to fetus. In general, the transmission of T. gondii is more efficient in the later half of gestation, mostly related to the anatomy and immune factors. For example, the thickness of the placenta varies with gestation; in early pregnancy, placental barrier of humans is 50–100 μ m thick and progressively decreases to 2.5–5 μ m at the end of pregnancy, allowing tachyzoites to more easily invade trophoblasts by the end of the gestational course (Blaszkowska and Góralska, Reference Blaszkowska and Góralska2014). Additionally, the internal cytotrophoblast layer is discontinuous, with its cells number decreasing during the gestational period. Infection early in gestation is clinically more severe, as reduced expression of Toll-like receptors in trophoblast cells during the first trimester of pregnancy may indicate a reduced ability of early placental cells to engage the immune response to intrauterine infection (Blaszkowska and Góralska, Reference Blaszkowska and Góralska2014).

Transplacental transmission of T. gondii infection generally occurs when a woman becomes infected during pregnancy. Rarely, congenital transmission occurs in women infected just before pregnancy or during chronic infection (Villena et al., Reference Villena, Chemla, Quereux, Dupouy, Leroux, Foudrinier and Pinon1998; Elbez-Rubinstein et al., Reference Elbez-Rubinstein, Ajzenberg, Dardé, Cohen, Dumètre, Yera, Gondon, Janaud and Thulliez2009). In addition, in immunosuppressed women, reactivation/reinfection of an infection acquired before pregnancy can lead to congenital toxoplasmosis but is rare (Peyron et al., Reference Peyron, Wallon, Kieffer, Garweg, Wilson, Nizet, Maldonado, Remington and Klein2016).

Transplacental infection can lead to a wide variety of manifestations in the fetus and infant including spontaneous abortion, stillbirth; it can also cause severe disease in live infant, but most children are asymptomatic at birth. Although T. gondii may sometimes cause sporadic abortion, there is no evidence that it causes habitual abortion. Most severe cases of prenatally acquired toxoplasmosis were reported first with the predominant manifestation of encephalomyelitis. Historically, the first confirmed case of congenital toxoplasmosis was in an infant girl who was delivered full term by Caesarean section on 23 May 1938 at Babies Hospital, New York (Wolf et al., Reference Wolf, Cowen and Paige1939). The girl developed convulsive seizures at 3 days of age and lesions were noted in the maculae of both eyes through an ophthalmoscope. She died of toxoplasmosis when 1-month-old and an autopsy was performed. At post-mortem, brain, spinal cord and right eye were removed for examination. Free and intracellular T. gondii were found in the lesions of encephalomyelitis and retinitis, and viable T. gondii was isolated in mice, rats and rabbits inoculated with tissues from the girl (Wolf et al., Reference Wolf, Cowen and Paige1939).

In early 1950s, Dr Albert Sabin proposed a triad of signs: hydrocephalus or microcephalus, intracranial calcification and retinochoroiditis. This triad has been useful in drawing attention to prenatal toxoplasmosis. A better understanding came from the work of Eichenwald (Reference Eichenwald and Siim1960), who found asymptomatic and clinical toxoplasmosis in many children in 1950s in Austria. Although the study by Eichenwald (Reference Eichenwald and Siim1960) from selected cases before treatment (prenatal and postnatal) of infected children became a routine, it pointed that toxoplasmosis can cause serious illness in children including both generalized and neurological disease (Dubey and Beattie, Reference Dubey and Beattie1988). As stated earlier, the most common manifestation of prenatal toxoplasmosis is ocular disease, sometimes presented as microphthalmy, cataracts, strabismus or nystagmus and even total blindness.

Hydrocephalus is the most dramatic sign of congenital toxoplasmosis, and occurs in approximately 4% of symptomatic children (Hutson et al., Reference Hutson, Wheeler, McLone, Frim, Penn, Swisher, Heydemann, Boyer, Noble, Rabiah, Withers, Montoya, Wroblewski, Karrison, Grigg and McLeod2015). Initially, it was considered to be due to the blockage of aqueduct of Sylvius. Recently, 4 anatomical patterns of hydrocephalus were reported: (i) obstruction of aqueduct of Sylvius, occurring in 43% of cases, (ii) obstruction of foramina of Monroe occurring in 25% of cases, (iii) mixed aqueductal and foraminal obstruction, occurring in 11% of cases, and (iv) with no obstructive pathogenesis, and was seen in 21% of cases (Hutson et al., Reference Hutson, Wheeler, McLone, Frim, Penn, Swisher, Heydemann, Boyer, Noble, Rabiah, Withers, Montoya, Wroblewski, Karrison, Grigg and McLeod2015). Ocular symptoms are the most common signs of congenital toxoplasmosis.

Most prenatal infections are sub-clinical at birth. Disease, if present in the neonatal period, is likely to be severe, invariably with neurological signs and often with signs of generalized infection. Such patients rarely recover without serious sequelae. Disease appearing in the first few months of life is usually less severe and is manifested by nystagmus, convulsions, bulging fontanelle and abnormal increase in skull circumference. Such patients sometimes develop normally.

It is likely that many cases of prenatal toxoplasmosis are missed because of difficulty in diagnosis. Couvreur et al. (Reference Couvreur, Desmonts, Tournier and Szusterkac1984), who diagnosed prenatal toxoplasmosis in 210 babies aged 0–10 months, found premature birth, intrauterine growth retardation or both in 17%, hyperbilirubinemia in 10%, hydrocephaly or microcephaly in 9%, intracranial calcification in 11% and retinochoroiditis in 22%. Infection was fatal in 2 of the 210, severe in 10%, mild without neurological signs in 34% and subclinical in 55%. It is noteworthy that over half of the babies born with T. gondii infection had no clinical manifestations. As noted by Eichenwald (Reference Eichenwald and Siim1960) earlier, in congenitally infected children, virtually all organ systems may be affected (Peyron et al., Reference Peyron, Wallon, Kieffer, Garweg, Wilson, Nizet, Maldonado, Remington and Klein2016).

An important question concerns the subsequent fate of subclinically infected babies. Many of them develop retinochoroiditis, although it may not manifest until later in childhood, or even in adult life. In a follow-up of 11 congenitally infected children without symptoms at birth, 9 (82%) developed lesions within 20 years; 4 (36.6%) of them developed retinal scars that impaired vision, 5 (45.5%) developed scars without affecting vision (Koppe et al., Reference Koppe, Loewer-Siege and Roever-Bonnet1986). In a 14-year follow-up of 327 congenitally infected children in Lyon, France, 95 (29%) had lesions despite treatment for toxoplasmosis. At the final examination, 60 (18%) had lesions only in the eyes, 35 (11%) had CNS lesions (intracerebral calcification in 31, hydrocephalus in 6 and microcephalus in 1) (Wallon et al., Reference Wallon, Kodjikian, Binquet, Garweg, Fleury, Quantin and Peyron2004). In a study in the USA, 11 of 120 congenitally infected children (many with obvious symptoms) recruited in a treatment programme died within 4 years despite treatment (McLeod et al., Reference McLeod, Boyer, Karrison, Kasza, Swisher, Roizen, Jalbrzikowski, Remington, Heydemann, Noble, Mets, Holfels, Withers, Latkany and Meier2006a).

The morbidity of congenital toxoplasmosis in children is very high and true suffering may be underestimated (Havelaar et al., Reference Havelaar, Kemmeren and Kortbeek2007; Bénard et al., Reference Bénard, Petersen, Salamon, Chêne, Gilbert and Salmi2008; Stillwaggon et al., Reference Stillwaggon, Carrier, Sautter and McLeod2011; Torgerson and Mastroiacovo, Reference Torgerson and Mastroiacovo2013; El Bissati et al., Reference El Bissati, Levigne, Lykins, Adlaoui, Barkat, Berraho, Laboudi, El Mansouri, Ibrahimi, Rhajaoui, Quinn, Murugesan, Seghrouchni, Gómez-Marín, Peyron and McLeod2018; Binquet et al., Reference Binquet, Lejeune, Seror, Peyron, Bertaux, Scemama, Quantin, Béjean, Stillwaggon and Wallon2019; Picone et al., Reference Picone, Fuchs, Benoist, Binquet, Kieffer, Wallon, Wehbe, Mandelbrot and Villena2020). One study estimated 1.2 million disability-adjusted life years and an estimated 190 100 cases globally (Torgerson and Mastroiacovo, Reference Torgerson and Mastroiacovo2013).

The risk of congenital infection is lowest when mother becomes infected in the first trimester (10–15%) and highest when mother acquires infection during the third trimester (Table 1). If maternal infection occurs early in pregnancy, it results in fewer infected babies, but they are more severely affected than the greater number of infected babies born when infection is acquired later in pregnancy. The highest risk to the fetus is when infection is acquired at 10–24th week of gestation. As will be seen in Table 1, most of this information on the transmission of congenital toxoplasmosis is derived from studies in France. In their pioneering study, Desmonts and Couvreur (Reference Desmonts and Couvreur1974a, Reference Desmonts and Couvreurb) reported congenital toxoplasmosis in 210 children born at 1 hospital in Paris; approximately 26% were subclinically infected at birth. Only about 10% were clinically affected – 6% mildly and 4% severely, and up to 3% died in the neonatal period. In a subsequent study from the same hospital, Daffos et al. (Reference Daffos, Mirlesse, Hohlfeld, Jacquemard, Thulliez and Forestier1994) reported clinical outcome in 148 infected fetuses of 2030 mothers who seroconverted during pregnancy. Based on ultrasound examinations, they found that 48, 12 and 3% of fetuses had cerebral ventricular dilatations when mothers became infected in early (<16 weeks), middle (17–23 weeks) and late (after 24 weeks) gestation, respectively (Daffos et al., Reference Daffos, Mirlesse, Hohlfeld, Jacquemard, Thulliez and Forestier1994). In a multicentre European study of 255 congenitally infected children, gestational age at the time of seroconversion in mothers was correlated with cerebral lesions but not retinochoroiditis (Gras et al., Reference Gras, Wallon, Pollak, Cortina-Borja, Evengard, Hayde, Petersen and Gilbert2005). In this study, 51 of 255 infants had 1 or more lesions, and 9 had both intracranial and ocular lesions. Of these, 4 of 55 children died (at 13 months, 11 months, 3 months and 7 days of age). The mother of the baby that died at 1 week of age had seroconverted between 5 and 31 days of gestation and she had received spiramycin prophylaxis from 32nd week until delivery (Gras et al., Reference Gras, Wallon, Pollak, Cortina-Borja, Evengard, Hayde, Petersen and Gilbert2005). The frequency and severity of clinical disease in congenitally infected children in France and Austria has decreased dramatically in the last decade, perhaps because of improved early detection and treatment. Ultrasound sonography can aid the determination of severity of lesions in the fetus (Codaccioni et al., Reference Codaccioni, Picone, Lambert, Maurice, Pomar, Winer, Guibaud, Lavergne, Saliou, Quinio, Benachi, Noel, Ville, Cuillier, Pomares, Ferret, Filisetti, Weingertner, Vequeau-Goua, Cateau, Benoist, Wallon, Dommergues, Villena and Mandelbrot2020).

Table 1.

Rate of congenital Toxoplasma gondii transmission according to the gestational age of maternal seroconversion in France^a

^a Women who seroconverted during pregnancy were treated with anti-T. gondii drugs to prevent fetal transmission and damage to the fetus.

^b No. of women who seroconverted during pregnancy.

A recent study in France retrospectively evaluated 88 cases of congenital toxoplasmosis with ultrasound anomalies diagnosed by fetal medicine experts, 45 (51.1%) had one or more cerebral lesions, the most common lesion being intracranial hyperechogenic cerebral nodular foci (Codaccioni et al., Reference Codaccioni, Picone, Lambert, Maurice, Pomar, Winer, Guibaud, Lavergne, Saliou, Quinio, Benachi, Noel, Ville, Cuillier, Pomares, Ferret, Filisetti, Weingertner, Vequeau-Goua, Cateau, Benoist, Wallon, Dommergues, Villena and Mandelbrot2020). In Table 2, initial data from screening studies are listed; at that time only a few follow-up studies on infected children were undertaken. Subsequently, many of these children were followed clinically for 4 or more years, and data included in the study were reported (The SYROCOT, 2007). Of 691 congenitally infected children from Europe, Brazil, Colombia and the USA, 24% had at least 1 clinical manifestation, 185 had ocular lesions and 13% had intracerebral calcification (The SYROCOT, 2007).

Table 2.

Congenital T. gondii infection in humans based on prenatal or postnatal screening^a

^a Modified from Dubey (Reference Dubey2010).

^b CNS, central nervous system signs; ICC, intracerebral calcification; NS, not stated; RC, retinochoroiditis.

^c Of 3708 mothers, 7 seroconverted during pregnancy. One infected fetus with abnormal prenatal ultrasound identified by prenatal screening, and infections in 3 babies were found by cord blood screening.

^d Of 2786 screened, 19 mothers seroconverted during pregnancy and 14 children were born infected. Three children were found infected by screening of 532 newborns; 8 of these infected children were selected for The SYROCOT analysis because diagnosis of cerebral lesion was done with tomography; those studies based on ultrasound were discarded (personnel communication from Gomez-Marin to J.P.D-February 25, 2021).

^e In 2007, there were 818 700 live births in France through the national screening programme; 272 congenital T. gondii-infections were recognized; 160 infections were diagnosed postnatally (130 at the age of 2 months, 22 between 2 months and 1 year). Of 235 cases, infection was acquired in first trimester in 17 (7%), 83 (35%) in the second trimester and 135 (58%) in third trimester.

^f Of 1624 mothers who seroconverted during pregnancy. Lesions in utero in 5, 20 at birth, 21 after birth. RC lesions discovered at birth in 2, in the first year in 20 and third year in 5.

^g In a multicentre retrospective study of 16 362 women in Barcelona in 1999, seroprevalence was 28.6% with primary infection of 1.02 per 1000 susceptible women; 9 of 12 susceptible women seroconverted during pregnancy. Out of 5 infected children, 4 were asymptomatic at birth; outcome of fifth infant was not stated.

As stated earlier, 60–70% of babies born from infected mothers escape infection. The severity of toxoplasmosis in the fetus or the infant is not related to the degree of symptoms of T. gondii infection in the mother. In 1 study that retrospectively examined risk factors among women who gave birth to infected children, 52% could not recall being sick (Boyer et al., Reference Boyer, Holfels, Roizen, Swisher, Mack, Remington, Withers, Meier and McLeod2005). In another study from a hospital in Lyon, France, of 603 women who seroconverted during pregnancy, only 36 (5%) had clinical symptoms (Dunn et al., Reference Dunn, Wallon, Peyron, Petersen, Peckham and Gilbert1999). In 161 of these 603 women (504 were treated for toxoplasmosis), infection was transmitted to their fetuses; 5 of them aborted, 3 were stillborn. Most of the 153 live born children were followed for 54 months after birth; 41 (27%) developed clinical signs (33 had retinochoroiditis, 14 had intracerebral calcification, 8 had combinations of signs, 1 child died when 8 days old) (Dunn et al., Reference Dunn, Wallon, Peyron, Petersen, Peckham and Gilbert1999).

The severity of symptoms is primarily related to the trimester of pregnancy when the mother becomes infected with T. gondii (Table 1). However, T. gondii genotype might be another factor, and this topic was reviewed recently (Dardé et al., Reference Dardé, Mercier, Su, Khan, Grigg, Weiss and Kim2020; Mcleod et al., Reference McLeod, Cohen, Dovgin, Finkelstein, Boyer, Weiss and Kim2020). Toxoplasma gondii strains are grouped into clonal Type I, II, III and atypical, based on different systems of genotyping (Dardé et al., Reference Dardé, Mercier, Su, Khan, Grigg, Weiss and Kim2020). Type II and III T. gondii strains predominate in Europe and North America, and Type I is rare. A different situation prevails in South America. The T. gondii strains from Brazil are mostly atypical and clonal strains are rare. In France, most strains isolated from congenital infections are Type II and the severity of congenital toxoplasmosis is related to the trimester of pregnancy when mother becomes infected (Dardé et al., Reference Dardé, Mercier, Su, Khan, Grigg, Weiss and Kim2020). However, in Brazil, women who became infected during the third trimester of pregnancy during oocyst-associated outbreaks of T. gondii had congenitally infected children with severe toxoplasmosis (Conceição et al., Reference Conceição, Belucik, Missio, Gustavo Brenner, Henrique Monteiro, Ribeiro, Costa, Valadão, Commodaro, de Oliveira Dias and Belfort2021). The severity of congenital toxoplasmosis in Brazil in comparison with France is thought to be associated with atypical T. gondii genotypes (Dubey et al., Reference Dubey, Lago, Gennari, Su and Jones2012). However, compared with France, relatively few strains from congenitally infected children in Brazil have been isolated and fully genotyped; 14 genotypes were reported (Carneiro et al., Reference Carneiro, Andrade, Costa, Pinheiro, Vasconcelos-Santos, Ferreira, Su, Januário and Vitor2013). There was no association of genotype with the severity of ocular lesions. However, in the USA, by using a serotyping assay, ocular toxoplasmosis and different anatomical patterns of hydrocephalus were associated with T. gondii Type II than in non-Type II (McLeod et al., Reference McLeod, Boyer, Lee, Mui, Wroblewski, Karrison, Noble, Withers, Swisher, Heydemann, Sautter, Babiarz, Rabiah, Meier and Grigg2012). It should be noted that serotyping has limited efficiency in distinguishing genotypes.

Estimates of congenital transmission

An estimate of the incidence of clinically manifest prenatal toxoplasmosis may be obtained in 3 ways: first, from reports of observed cases and, second, from calculations based on the infection rate during pregnancy, and third, from screening of babies at birth. Representative examples of estimates of congenital infections based primarily on screening of mothers during pregnancy are given in Table 2. Many countries have some surveillance programmes (van der Giessen et al., Reference van der Giessen, Deksne, Gómez-Morales, Troell, Gomes, Sotiraki, Rozycki, Kucsera, Djurković-Djaković and Robertson2021). Congenital infections noted during acute outbreaks of toxoplasmosis summarized recently (Dubey, Reference Dubey2021) were excluded from Table 2. Data from the National Collaborative Chicago-based Toxoplasmosis Study in the USA (Boyer et al., Reference Boyer, Holfels, Roizen, Swisher, Mack, Remington, Withers, Meier and McLeod2005, Reference Boyer, Hill, Mui, Wroblewski, Karrison, Dubey, Sautter, Noble, Withers, Swisher, Heydemann, Hosten, Babiarz, Lee, Meier and McLeod2011; McLeod et al., Reference McLeod, Boyer, Karrison, Kasza, Swisher, Roizen, Jalbrzikowski, Remington, Heydemann, Noble, Mets, Holfels, Withers, Latkany and Meier2006a, Reference McLeod, Khan, Noble, Latkany, Jalbrzikowski and Boyerb, Reference McLeod, Kieffer, Sautter, Hosten and Pelloux2009, Reference McLeod, Cohen, Dovgin, Finkelstein, Boyer, Weiss and Kim2020) are not included in Table 2.

More information is available from countries that have screening (prenatal or postnatal) programmes (Tables 2 and 3).

Table 3.

Congenital toxoplasmosis (CT) in children, based on cases reported at national level in the surveillance system (Toxosurv/National Reference Centre on Toxoplasmosis)^a

^a Courtesy of Toxosurv/National Reference Centre on Toxoplasmosis.

Most of the estimates of congenital infections are from studies that are 10–40 years old, but they are listed in Table 2 to provide perspective. Only Austria and France have compulsory screening of pregnant women for T. gondii infection. Rates of congenital transmission are difficult to compare among countries because of the different methodology used. In some studies, only seroconversion during pregnancy was reported (Sagel et al., Reference Sagel, Krämer and Mikolajczyk2011). One could guess/estimate congenital infection based on the assumption of 50% rate of transmission from mother to fetus. Although there is no national screening for toxoplasmosis in Brazil, valuable information has been obtained from testing of children at few hospitals; these studies were reviewed in detail previously (Dubey et al., Reference Dubey, Lago, Gennari, Su and Jones2012) and summarized here in Table 2.

Prophylactic treatment during pregnancy and prenatal screening

Prevention of infection of the fetus by prophylactic treatment of the mother depends on the delay between maternal infection and its transmission to the fetus. It is also hoped that if infection is already present in the fetus, treatment may limit its ill effects. Treatment is begun as soon as possible during the prenatal period. In Austria and France, it is by spiramycin before the 20th week of pregnancy and thereafter by pyrimethamine and sulfonamide (Picone et al., Reference Picone, Fuchs, Benoist, Binquet, Kieffer, Wallon, Wehbe, Mandelbrot and Villena2020).

A large European multicentre cohort study found no evidence that pre-natal treatment with either spiramycin or sulphonamide combined with pyrimethamine influenced maternal transmission (Gilbert et al., Reference Gilbert, Gras, Wallon, Peyron, Ades and Dunn2001). The relative risk of mother-to-child transmission of T. gondii compared to Lyon, France (women treated) was 1.24 in Austria (women treated), 0.59 in Denmark (no treatment) and 0.65 in the Netherlands (50% treated, 50% not treated) (Gilbert et al., Reference Gilbert, Gras, Wallon, Peyron, Ades and Dunn2001). A meta-analysis of 22 European cohorts found weak evidence that treatment started within 3 weeks of seroconversion reduced mother-to-child transmission compared with treatment started after 8 weeks or more (The SYROCOTT, 2007). On the other hand, the number of congenital infections, based on the mothers testing screening in Lyon, France, decreased after 1992 (46.6% after 1992 vs 59.4% from 1987–1991) when screening of susceptible women became mandatory and antenatal treatment was initiated as soon as the diagnosis was made (Wallon et al., Reference Wallon, Peyron, Cornu, Vinault, Abrahamowicz, Kopp and Binquet2013). In a recent randomized multicentre trial of sulfadiazine plus pyrimethamine (SzP), and spiramycin (Sp) in 143 mothers (73 SzP group, 70 Sp group) who seroconverted during pregnancy, the transmission rate of congenital toxoplasmosis was 2-fold lower in the SzP group (18.5%) than the Sp group (30%) (Mandelbrot et al., Reference Mandelbrot, Kieffer, Sitta, Laurichesse-Delmas, Winer, Mesnard, Berrebi, Le Bouar, Bory, Cordier, Ville, Perrotin, Jouannic, Biquard, d'Ercole, Houfflin-Debarge, Villena and Thiébaut2018). Cerebral lesions were noted in 0/73 in the SzP group vs 6 of 70 in the Sp group, indicating the effectiveness of therapy in reducing damage to fetal tissues.

One current practice is to start treatment with spiramycin if the woman becomes infected in the first or early second trimester of pregnancy, and then perform amniocentesis to detect fetal infection (Montoya, Reference Montoya2018). If fetal infection is detected, then therapy is switched to pyrimethamine and sulfadiazine. Pyrimethamine and sulfadiazine may be used initially in the late second and third trimesters when acute infection is detected.

French T. gondii programme is based on serological screening of mothers to give prophylactic measures to seronegative women to avoid maternal infection. When seroconversion occurs during pregnancy, in complement to prophylactic treatment, a prenatal diagnosis is recommended. This prenatal diagnosis is based on monthly ultrasonography examination and molecular testing for T. gondii DNA on amniotic fluid. Amniocentesis must be performed after 18 amenorrhea weeks and 4 weeks after maternal infection. In case of detection of DNA (PCR positive) in amniotic fluid, diagnosis of congenital toxoplasmosis is made. However, if the PCR is negative, this does not mean that the fetus is free of congenital infection. Children must be followed at birth to detect congenital infection. In France, since surveillance of congenital toxoplasmosis by the National Reference Centre for Toxoplasmosis (beginning in 2007), approximately 10% of false-negative diagnoses are identified annually (data from NRC for toxoplasmosis). One explanation for these observations is that T. gondii is arrested in the placenta and crosses the barrier a few days to weeks later.

Each country needs to evaluate the cost of screening pregnant women, treatment of congenitally infected children and human suffering based on resources and the prevalence of T. gondii in general population (Scallan et al., Reference Scallan, Hoekstra, Angulo, Tauxe, Widdowson, Roy, Jones and Griffin2011; Jones et al., Reference Jones, Kruszon-Moran, Elder, Rivera, Press, Montoya and McQuillan2018; Suijkerbuijk et al., Reference Suijkerbuijk, van Gils, Bonačić Marinović, Feenstra, Kortbeek, Mangen, Opsteegh, de Wit and van der Giessen2018; Binquet et al., Reference Binquet, Lejeune, Seror, Peyron, Bertaux, Scemama, Quantin, Béjean, Stillwaggon and Wallon2019; Bobić et al., Reference Bobić, Villena and Stillwaggon2019). Stillwaggon et al. (Reference Stillwaggon, Carrier, Sautter and McLeod2011) provided an extensive guideline for estimating the costs of preventive maternal screening for and the social costs resulting from toxoplasmosis based on studies in Europe and the USA. While estimating these costs, the value of all resources used or lost should be considered, including the cost of medical and non-medical services, wages lost, cost of in-home care, indirect costs of psychological impacts borne by the family for lifetime care of a substantially cognitively impaired child; cost of fetal death was estimated to be 5 million dollars (Stillwaggon et al., Reference Stillwaggon, Carrier, Sautter and McLeod2011). A study on the cost-effectiveness of screening from Austria estimated a lifetime cost of 103 Euros per birth under prenatal screening compared with 323 Euros without screening (Prusa et al., Reference Prusa, Kasper, Sawers, Walter, Hayde and Stillwaggon2017). Although it is unethical to value human life in terms of dollars, each nation must balance public funding for all the needs of its people, including the prevention of crippling ailments.

Where it has been carried out with thoroughness, persistence and determination, as in France, education appears to have contributed to a reduction in the incidence of T. gondii infection during pregnancy. It should be included in the instructions given in antenatal clinics and by obstetricians and midwives dealing with individual patients. Individual instruction given in person is likely to be most effective but should be supplemented by booklets printed in the various languages of the patients and by videos in the waiting rooms of antenatal clinics.