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A rare fetopathy characterized by ocular, visceral or intracranial lesions secondary to maternal primo-infection by Toxoplasma gondii (Tg).
ORPHA:858Classification level: Disorder
- Mother-to-child transmission of toxoplasmosis
- Toxoplasma embryofetopathy
- Toxoplasma embryopathy
- Prevalence: Unknown
- Inheritance: Not applicable
- Age of onset: Antenatal, Neonatal, Infancy
- ICD-10: P37.1
- OMIM: -
- UMLS: C0040560
- MeSH: D014125
- GARD: -
- MedDRA: 10010652
Given its infectious origin, incidence of congenital toxoplasmosis (CTX) is variable over time and geographically. Screening policies and methods also influence prevalence calculation. The global annual prevalence at birth is estimated to be 1.5/1000.
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 manifestation is seizures; nystagmus, hypotonia and, later, delay of developmental milestones acquisition can be seen. The chorioretinitis - intracranial calcifications - hydrocephalus triad is present in at least 10% of cases. Ocular involvement may develop after months or years, most frequently with chorioretinitis, followed by microphthalmia and strabismus. Visual impairment is highly dependent on the parasite genotype, and probably on prenatal and postnatal treatments.
CTX is caused by the mother's primo-infection by Tg, an intracellular protozoan parasite of the Apicomplexa phylum, and transmission to the fetus by trans-placental infection. Nearly 25% of exposed fetuses are infected. Mother is infected by Tg through ingestion of ooccysts present in cat faeces and soil, or of cysts present in uncooked meat.
Diagnosis relies on evidence of infection in the fetus, the infant or the child with a history of maternal primo-infection during pregnancy or up to 6 months before conception. Given the poor specificity of clinical signs observed in Tg infection, serological findings and PCR amplification of Tg specific sequences are the main diagnostic clues. RT-PCR targeting repetitive DNA segments is reported to be more sensitive and not less specific than previous tests.
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.
Fetal ultrasonography and/or magnetic resonance imaging (MRI) detect and characterize brain, cardiac or placental anomalies. Diagnosis is confirmed only with serological or PCR findings of Tg infection in the mother and the amniotic fluid. Amniocentesis should be performed at least 4 weeks after the mother's seroconversion to avoid false negative results due to latency.
Management and treatment
In several countries, a systematic serological status follow-up of each pregnant woman is organized in order to diagnose and treat early maternal and fetal infections. 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 is highly dependent on the parasite genotype, the gestational age at maternal infection and on the timing of prenatal and postnatal treatment.