Explore UAB

History: 7-day-old infant boy referred for evaluation of bilateral enlargement of the lateral ventricles that had been noted on a week-36 fetal ultrasound performed on the mother. Routine ultrasounds performed at gestational weeks 13, 23 and 32 were normal. Vaginal bleeding at week 36 led to an urgent ultrasound focused on the placenta and the official report noting the cerebral abnormality did not become available for several weeks. A repeat ultrasound at week 38.5 confirmed the abnormality. After an uneventful full-term vaginal delivery, the infant weighed 3400 gm and had an Apgar score of 9 at 1 minute and 10 at 5 minutes. The mother had two previous pregnancies and two normal deliveries.

Epidemiology: The mother is a lifelong resident of Lima; she had full normal childhood vaccinations. No known TB exposure. No HIV risk factors.

Physical Examination: Afebrile. Chest clear. Cardiovascular normal. No hepatosplenomegaly. Skin without rash. HEENT: Funduscopic examination of left eye [Image A] and right eye [Image B] are shown. CNS: examination by a pediatric neurologist at the maternity hospital was normal, as was audiometric examination.

Laboratory Results: Hb 12.0. Hct 35. WBC 6.1 with 30 neutrophils, 62 lymphs, 5 monos, 3 eos. Platelets 336,000. Total bilirubin 7.0 with 6.05 direct. Normal hepatic transaminases. CSF: 26 WBCs, 85% mononuclear. Protein 131 mg/dl (N<50). Glucose 29 mg/dl. HIV, RPR negative. Normal chest x-ray. CT scan is shown [Images C & D].

Discussion: A Toxoplasma IgM on the infant’s serum was 3.8 (N<1.1). Testing for HSV1, HSV2, Rubeola, and CMV IgM was negative. Congenital rubella has been eradicated from Perú. The funduscopic examination revealed a normal left eye and the right eye had uveitis with a vitreal reaction and a large cotton wool spot but no retinal scarring. Focal necrotizing retinitis and scarring is only present at birth in 20% and usually occurs later after birth if untreated. The CT scan [Images C & D] was read as showing bilateral enlargement of the lateral ventricles with both periventricular and sub-cortical calcification. An MRI [Images E & F] showed the ventricular dilatation, periventricular leukomalacia, decreased size of the corpus callosum, and there were petechial hemorrhages with foci of hemosiderin deposition [punctate enhancing lesions in Image F]. In retrospect the mother recalled a 1-day flu like illness without fever during the 29th week of gestation for which she did not seek medical care. Testing for CMV, EBV, and rubeola IgG in the mother was positive. Toxoplasma IgG in the mother was 1018 (N<3); no IgM for Toxoplasma was performed.

Toxoplasma gondii is a protozoan that has a sexual cycle in the intestines of cats and felines. Humans become infected from ingestion of cat feces, or by ingestion of undercooked beef (e.g., Carpaccio) or other meat from animals that harbored tissue cysts after infection from cats. Acute Toxoplasma infection is asymptomatic or may cause a mononucleosis-like illness in immunocompetent hosts who then develop dormant tissues cysts. Serious disease may subsequently occur in immunosuppressed hosts. In the case of acute infection during pregnancy, congenital infection of the fetus occurs due to trans-placental transmission. Maternal infection is often mild and may not be noticed by the pregnant woman. Infection occurs throughout the world but seems highest in Europe, Central America, Brazil, and central Africa.

Risk of transmission to the fetus varies according to gestational age during an acute maternal infection. As gestational age increases, the risk of fetal infection increases but the severity of congenital infection decreases. Without treatment of the mother, fetuses infected during early pregnancy usually die in utero or soon after birth; survivors have severe neurologic or ophthalmologic sequelae. Fetuses infected in the second or third trimester typically have mild or subclinical disease at birth. However, in these cases disease in the infant will progress if not aggressively treated.

The classical clinical triad of chorioretinitis, hydrocephalus, and intracranial calcification occurs in 10% or less of cases. Most newborns (up to 90%) with congenital toxoplasmosis have no manifestations on routine examination at birth and are often missed until much later in the disease course. This diagnosis in our patient was fortuitously made because the incidental ultrasound finding at week 36 led to more detailed investigation in the neonatal period. In addition to the typical imaging findings and evidence of chorioretinitis, the CSF pleocytosis and elevated protein are typical. In severe congenital disease, in addition to CNS and eye findings there may be jaundice, hepatosplenomegaly, fever, lymphadenopathy, pneumonitis, thrombocytopenia and microphthalmia.

Differential diagnosis includes congenital rubella, CMV and syphilis. Diagnosis in the newborn generally relies on a positive serum IgM for Toxoplasma, though increasingly PCR of CSF is being used [Pediatr Infect Dis J. 2014 Jan 17]. Since IgG passes through the placenta, a positive IgG may reflect only a chronic maternal infection. As fetal IgM may revert to normal by time of birth in fetuses infected in early pregnancy, a negative test does not rule out infection. Cases where there is a strong clinical suspicion but a negative IgM should undergo more sophisticated serological testing at a reference laboratory.

There is no danger of congenital infection from women infected prior to pregnancy. Chronic infection is manifest by a positive IgG in the absence of Toxoplasma IgM. In some countries, especially in Europe, routine serial screening throughout pregnancy is undertaken. Women with IgG at the onset of pregnancy need no further testing. Negative women are tested at regular intervals for the presence of IgM and seroconverters in the first trimester are offered treatment to prevent congenital infection. Policy in the USA, Canada and the UK, as well as Peru, is not to routinely test for Toxoplasma. From 400 to 4,000 cases of congenital toxoplasmosis occur each year in the USA but routine testing is not thought to be cost effective.

This child has been started on treatment with sulfa, pyrimethamine and folinic acid for a minimum of 1 year to prevent progression of infection.