Bilateral ocular involvement in congenital toxoplasmosis: A case report and literature review

Case report

A two-month-old boy was referred for congenital infection due to the presence of bilateral congenital cataract on the ophthalmic examination. On admission, his weight was 4 kg, length 59 cm, and head circumference 38 cm (being the 10th, 25th and under the 3rd centile, respectively); vital signs were normal. He had no eye contact with bilateral leucocoria and microphthalmos. Remaining physical examination was unremarkable. He was born at 38 weeks’ gestation with a birth weight of 2.9 kg and was admitted in neonatal intensive care owing to transient tachypnoea for two days. His mother had missed prenatal visits during pregnancy and had not been screened for toxoplasma infection. Toxoplasma-specific immunoglobulin IgM on testing the child was inconclusive, but toxoplasma-specific IgG was 64 IU/ml (reference value: 1–3 IU/ml); while polymerase chain reaction (PCR) testing of Toxoplasma gondii in blood and cerebrospinal fluid (CSF) was negative (Table 1). Other laboratory analyses were unremarkable. Tests on the mother showed anti-T. gondii IgM to be doubtful, anti-T. gondii IgG >650 IU/ml with high avidity (Table 2). After 18 days, anti-T. gondii IgG on the infant was noted to be significant (465 IU/ml) and the toxoplasma Sabin–Feldmann dye test was positive at 1/256. Evaluation for rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV) infection were negative. Magnetic resonance imaging scanning confirmed corpus callosum dysgenesis and mild dilatation in the third ventricle, with no calcification in brain parenchyma. As a diagnosis of congenital toxoplasmosis infection was thus confirmed, treatment with pyrimethamine, sulfadiazine, and leucovorin was initiated. A standard cataract extraction was performed; chorioretinitis was not detected. The child remains under follow-up.

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Table 1.

The results of laboratory tests of infant.

Assay performed	July 24, 2018	August 15, 2018	April 8, 2019	July 29, 2019
lgG anti-T. gondii (IU/ml)	64,77	465,4	>650	>650
lg M anti-T. gondii (IU/ml)	Inconclusive	Inconclusive	Negative	Negative
T. gondii PCR (blood)	Negative
T. gondii PCR (CSF)	Negative

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Table 2.

The results of laboratory tests of mother.

Assay performed	August 28, 2018
lgG anti-T. gondii (IU/ml)	>650
lgG avidity anti-T. gondii	83%
lg M anti-T. gondii (IU/ml)	inconclusive

Ig: Immunoglobulin; T. gondii: Toxoplasma gondii; PCR: polymerase chain reaction.

IgG: negative<1; positive ≥3.

IgG avidity: ≥ 60% shows past infection > 4 months ago.

IgM: negative<0.50; positive ≥0.60.

Discussion

Congenital toxoplasmosis is a worldwide disease causing severe clinical manifestations, especially ocular pathology. With an incidence rate of 1.5/1000 live births, this disease is an important cause of visual loss from chorio-retinal lesions in >82%.¹ Recent studies have shown that treatment given in utero and in the first year of life can reduce ophthalmological complications.² Since acute maternal infection is usually asymptomatic in cases 80%, serological screening is the only way to detect infected mothers. Untreated in pregnancy, the disease results in more severe clinical sequelae. ³ Conditions that increase the risk of maternal-fetal perinatal transmission include high parasite load, highly virulent strains of T. gondii, and maternal immunosuppression. ⁴ As the gestational age increases, so the risk of fetal transmission increases, while disease severity decreases. ⁵ Without treatment, most fetuses infected early in pregnancy die in utero or in the neonatal period, or develop severe neurological and ophthalmological sequelae. ⁶ The high avidity anti-T. gondii IgG in our patient’s mothers and the severe ophthalmological sequelae in the child suggest that maternal infection developed in the early stages of pregnancy.

Most (80%) congenital disease is asymptomatic, with no signs at birth. ⁷ However in symptomatic patients, the most common findings are chorioretinitis (80%), hydrocephalus (20%) and intracranial calcification (40%), sometimes causing seizure, as well as thrombocytopenia, anaemia, fever, rash, hepatosplenomegaly, lymphadenopathy, microphthalmia and cataract. ⁸ Congenital cataracts may also be caused by rubella, CMV, HSV and Treponema pallidum and secondary to prenatal drug exposure, radiation, or due to hereditary or prenatal/perinatal metabolic diseases of unknown cause. ⁹ Although the pathogenesis of cataracts in congenital toxoplasmosis is unknown, the choroid and the retina are usually affected; cataracts and iridocyclitis are secondary complications. An incidence of cataract was found to be 11.6% in 173 children with congenital toxoplasmosis. ¹⁰ Of all causes of congenital cataracts in India, T. gondii DNA was found in 32.7%. ⁹ Toxoplasma DNA was, however, found in 30%–40% in the aqueous humor in patients with congenital toxoplasmosis with ocular involvement. Low DNA amplification rates may reflect a low parasitic load in the aqueous humor (even in cases of acute infection) and/or early degradation of toxoplasma DNA. ¹¹

The diagnosis is based on maternal history and serology, detailed ophthalmological and neurological evaluation of the newborn, and the clinical findings. In the laboratory evaluation, Toxoplasma lgM and lgA titres are observed to drop rapidly in non-infected newborns at least 10 days after birth, while those who are infected may remain positive for weeks. lgG indicates a mother’s past infection. Transplacentally transmitted maternal toxoplasma IgG antibody is expected to decrease by 50% per month after birth and becomes negative within 6 to 12 months. ¹² Toxoplasma-specific IgG increases in the first year of life in infants with congenital infection. Our patient shows the importance of strict serological follow-up to confirm the diagnosis in cases with suspected congenital toxoplasmosis. Sabin–Feldman, a sensitive and specific neutralisation test for toxoplasma, is the standard reference test and titres >1:16 indicate acute toxoplasmosis.^13,14

Any case should undergo a full ophthalmological and neurological evaluation, including, lumbar puncture and neuroimaging. ⁷ An increase in CSF protein or mononuclear CSF pleocytosis and positive T. gondii PCR are keys. ¹⁵ A hearing test is recommended for all possible cases; in particular, the diagnostic auditory brainstem response (ABR) is preferred. ¹⁶

The recommended treatment regimen is pyrimethamine (2 mg/kg for the first 2 days, continued as 1 mg/kg once daily), sulfadiazine (50 mg/kg/dose every 12 h) and folinic acid (10 mg 3 times a week). A one-year combination therapy in infants with clinical signs of congenital toxoplasmosis is associated with a reduction in the risk of long-term complications and new-onset ocular complications. Glucocorticoids are added to the treatment if the protein of CSF is >1 g/dl and active chorioretinitis threatens vision. ⁴