Congenital toxoplasmosis (ORPHA:858)
A rare fetopathy characterized by ocular, visceral or intracranial lesions secondary to maternal primary infection by Toxoplasma gondii (Tg).
Epidemiology
Given its infectious origin, incidence of congenital toxoplasmosis (CTX) is variable over time and geographically. Screening policies and methods also influence prevalence calculation. Prevalence at birth is estimated to be 0.5 to 1.6/10 000 in Europe.
Clinical description
Clinical presentation is highly variable. Earlier infection is generally more severe but less frequent. Infections in the first trimester may result in miscarriage or fetal death in utero, whereas later ones may be limited to ocular anomalies. Intracranial calcifications, micro- or macrocephaly, ventricular dilatation and hydrocephalus, hepatomegaly, splenomegaly, cardiomegaly, ascites and intrauterine growth retardation can be observed in infected fetuses. When present, clinical manifestations at birth are maculopapular rash, jaundice, generalized lymphadenopathy, organomegaly, central nervous system anomalies and hyperbilirubinemia, anemia, and thrombocytopenia. The first neurologic manifestations are hypotonia, seizures, nystagmus, and, later, delay of developmental milestone acquisition can be seen. The triad of chorioretinitis, intracranial calcifications and hydrocephalus is present in at least 10% of clinical cases. Ocular involvement involves most frequently chorioretinitis, followed by microphthalmia and strabismus. New lesions of chorioretinitis or relapses may develop after months or years: Visual impairment is highly dependent on the parasite genotype, and probably on prenatal and postnatal treatments.
Etiology
CTX is caused by the mother's primary infection by Tg, an intracellular protozoan parasite of the Apicomplexa phylum, and the trans-placental infection of the fetus. Nearly 25% of exposed fetuses are infected. Mother is infected by Tg through ingestion of oocysts present in cat feces and soil, or of cysts present in uncooked meat.
Diagnostic methods
Diagnosis of pergravidic maternal infection is based on the detection of 1) a true seroconversion with appearance of IgG in a woman previously known to be uninfected, or if the first serology is already positive of 2) of a significant increase in IgG in the context of high IgM titters. The diagnosis of congenital toxoplasmosis relies on the detection of Tg DNA in amniotic fluid or in other products, or of a neosynthesis of IgG, IgM or IgA in the child after birth. Persistence of anti-Toxoplasma IgG at one year of age is considered as the gold standard for congenital toxoplasmosis diagnosis. RT-PCR targeting repetitive DNA segments should be used for the molecular diagnosis of congenital toxoplasmosis. Diagnosis of maternal and congenital infections should be confirmed by expert laboratories.
Differential diagnosis
Differential diagnosis includes other congenital infections (rubella, CMV, HSV1 and HSV2, regrouped with Tg infection in the TORCH syndrome) and pseudo-TORCH and Aicardi-Goutières syndromes.
Antenatal diagnosis
Fetal ultrasonography and/or magnetic resonance imaging (MRI) detect and characterize brain, cardiac or placental anomalies. Diagnosis is confirmed only with serological findings in the mother and with PCR findings of Tg infection the amniotic fluid. Fetal ultrasound examination should be repeated in the context of a proven maternal infection. Amniocentesis for PCR should be performed too, after 18 weeks of gestation, and at least 4 weeks after the mother's seroconversion to avoid false negative results. Ultrasound examinations should be more frequent if PCR on amniotic fluid is found to be positive.
Management and treatment
In several countries, a systematic serological status follow-up of each pregnant woman is organized in order to reduce the number of severely infected children. Seronegative pregnant women are tested regularly to detect seroconversion, with, if needed, a spiramycin-based treatment, expected to reduce vertical transmission. A pyrimethamine-sulphonamide combination is recommended in case of confirmed fetal infection. It is also used after 14 weeks of gestation to prevent vertical transmission. Neonates who are recognized as infected should also be treated even if they are asymptomatic at birth since complications may occur later. The benefits of prenatal and postnatal treatment remain to be quantified.
Prognosis
Prognosis is highly dependent on the parasite virulence, the gestational age at maternal infection and on the timing of prenatal and postnatal treatment.

                            Last update: 
                            August 2020


                            - Expert reviewer(s): 
                            Pr Martine WALLON