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Introduction
Although the American Congress of Obstetricians and Gynecologists does not currently
recommend universal screening of pregnant women for toxoplasmosis, screening by check-
ing maternal titers is available and inexpensive. Some clinicians offer this test routinely to all
women or to women with risk factors. We present a case of fetal exposure to toxoplasmosis
discovered by routine screening as a means to illustrate the present understanding of this
disease, neonatal evaluation, and treatment.
The Case
A 30-year-old, gravida 1, para 0 woman presents to establish routine prenatal care, which
includes screening laboratory tests for congenital infections. She screens positive for Toxo-
plasma gondii. The patient recalls no symptoms. She does not own a cat or handle animals
but has recently traveled to Thailand. She is referred to a maternal fetal medicine specialist
for further testing.
Ultrasonography at 16 weeks gestation reveals a fetus with average growth parameters
and grossly normal anatomy. The results of additional low-avidity IgM testing are positive,
indicating recent maternal toxoplasmosis infection. The patient starts spiramycin therapy
and continues to receive this therapy for the duration of found in litter boxes, soil, and contaminated water and plant
the pregnancy. An amniocentesis is performed at 18 weeks products. When ingested by humans and other mammals,
gestation, yielding a negative toxoplasmosis polymerase the oocyst transforms into the active tachyzoite, which trav-
chain reaction (PCR) result. She returns for multiple level els through the bloodstream and lymphatic system to infect
II ultrasonograms, all of which produce normal results. a variety of tissues. As the immune system responds to the
The patient and her husband consult with a neonatolo- infection, the tachyzoite is sequestered in tissue as the bra-
gist at 36 weeks gestation and review the recommended dyzoite or cyst form. The cyst can persist in tissue for many
neonatal evaluation. At 402/7 weeks estimated gestational years and, if ingested, can revert to the tachyzoite form and
age, she presents in spontaneous labor. Because of late de- cause disease. Humans become infected through the in-
celerations on fetal heart rate monitoring, the infant is de- gestion of oocysts or cysts, which are usually found in
livered by cesarean section. undercooked meat. Primary maternal infection leads to par-
A vigorous male infant weighing 2,673 g (second per- asitemia, and if the tachyzoite crosses the placenta, congen-
centile) is delivered. His head circumference is 33.5 cm ital toxoplasmosis may occur. (1) Rare cases of congenital
(12th percentile), and his length is 48.3 cm (eighth per- disease due to reactivation of latent disease in an immuno-
centile). The remainder of his examination ndings are compromised mother have been reported.
normal. He undergoes the preplanned evaluation. The re- The incidence of congenital toxoplasmosis ranges from
sults of noncontrast head computed tomography (CT) are 1 in 1,000 live births in some European countries to 1 in
negative for intracranial calcications or hydrocephalus. 10,000 in the United States. (1) The difference in incidence
Results of a dilated funduscopic examination are negative is related to risk factors for T gondii exposure. The parasite
for retinitis, deposits, and inltrates. A complete blood is more commonly found in warm, humid locations, where
count (CBC) with differential reveals a white blood cell the oocyst can easily replicate, leading to a high burden of
count of 17,800/mL (17.8 109/L), a hemoglobin level disease in tropical climates. The incidence is increased in
of 15.7 g/dL (157 g/L), hematocrit of 45% (0.45), and populations where the consumption of undercooked meats,
platelet count of 179 103/mL (179 109/L) with a dif- particularly lamb and pork, is common. Other risk factors
ferential of 74% neutrophils, 18% lymphocytes, and 8% include exposure to contaminated soil, water, or plant
monocytes. Hepatic function tests reveal the following: al- product and contact with infected cat feces. Vertical trans-
bumin, 3.3 g/dL (33 g/L); total bilirubin, 8.6 mg/dL mission increases with gestational age, from 5% in the rst
(147.1 mmol/L); direct bilirubin, 0.5 mg/dL (8.6 trimester to 32% in the third trimester. (2)
mmol/L); alkaline phosphatase, 126 U/L; serum glutamic
oxaloacetic transaminase, 77 U/L; and serum glutamic Findings
pyruvic transaminase, 12 U/L. The following evaluations Congenital toxoplasmosis is asymptomatic in up to 80%
are sent to the Palo Alto Toxoplasma Serology Laboratory: of patients. (3) When symptoms arise, they can occur at
maternal serum IgG and IgM T gondii titers (both posi- birth, in early infancy, or in later years. The neonatal and
tive); placenta T gondii DNA PCR (not detected); neona- infantile forms are more severe and often have central ner-
tal serum for T gondii IgG (positive), IgM (negative), and vous system and ocular manifestations. Generally, more se-
IgA (negative); neonatal serum T gondii DNA PCR (not vere disease correlates with earlier infection in utero. The
detected); and neonatal cerebrospinal uid T gondii DNA classic triad of neonatal disease includes intracranial calci-
PCR (not detected). cations, hydrocephalus, and chorioretinitis. However, the
The infant has an uneventful remaining nursery course presence of all 3 signs is uncommon, and other abnormal-
and is discharged 4 days after birth. At follow-up with the ities, such as hepatosplenomegaly, anemia, and cerebrospi-
pediatrician, the infant has normal weight gain and growth nal uid changes, may be present. Infants often present
in the rst month. He is scheduled to have periodic serum with seizures, hydrocephalus, or eye ndings. Later disease
quantitative immunoglobulin values and T gondii titers is usually localized to the eyes, with chorioretinitis being
measured through his rst birthday. the most common manifestation. (4)
Etiology
Toxoplasmosis is caused by the protozoa T gondii. The Evaluation
denitive host is felines, but a variety of mammals can be- Evaluation of a neonate suspected of having congenital
come infected and serve as intermediate hosts. The par- toxoplasmosis should include a complete history and
asite exists in 3 forms: oocyst, tachyzoite, and bradyzoite. physical examination, lumbar puncture, head CT, CBC
The oocyst is excreted by infected cats and is commonly with differential, detailed ophthalmologic examination,
and T gondii PCR and serologic testing. Characteristic ce- clearly dene best practices for prenatal maternal treatment
rebrospinal uid ndings include mononuclear pleocytosis and infant treatment. However, many studies indicate that
and high protein content. A head CT is recommended to maternal treatment with spiramycin from the time of sero-
evaluate for intracranial calcications. The sensitivity of conversion or low-avidity test (meaning as close to time of
head ultrasonography to detect smaller lesions makes it primary infection as possible) reduces the vertical transmis-
an unreliable screening tool. Hematologic abnormalities, sion by as much as 60% and decreases severity of disease in
such as anemia, thrombocytopenia, and eosinophilia, affected neonates. (7)(8)(10) This drug has been used in
may be seen on peripheral blood smear. An ophthalmo- pregnancy for toxoplasmosis since the 1970s and signi-
logic examination, preferably by a pediatric ophthalmolo- cantly lowers placental T gondii infestation. (11) Spiramy-
gist experienced with retinal disease, is essential. Ocular cin is a macrolide antibiotic that concentrates in the
ndings may include retinitis, chorioretinal scarring, cata- placenta without crossing to fetal circulation. It is not com-
ract, and microphthalmia. Blood, spinal uid, and placenta mercially available in the United States but can be pro-
samples should be evaluated for T gondii by PCR. Parasi- vided at no cost after application to the Food and Drug
temia is found in up to 50% of asymptomatic newborns. Administration for pregnant women with conrmed toxo-
(5) T gondii serologic test results can be difcult to inter- plasmosis. (7) Because it is well tolerated, many affected
pret, and consultation with an infectious disease expert is women continue to take spiramycin for the duration of
recommended. The clinician should ensure that samples pregnancy unless fetal disease is suspected.
are sent to an appropriate reference laboratory. Positive If fetal infection is suspected by imaging or amniocen-
neonatal T gondii IgM test results essentially conrm tesis, treatment should be directed at minimizing fetal dis-
the diagnosis. However, false-positive results related to ease by initiating pyrimethamine, sulfadiazine, and folinic
cross-contamination with maternal uids have been re- acid (PSF). Because of the higher incidence of transmis-
ported. Additional IgM titers may be considered. IgM will sion after 18 weeks gestation, some specialists empirically
typically normalize several days after birth if placental leak switch affected women to PSF after the 18th week through
was the cause, whereas in congenital disease IgM will re- the duration of the pregnancy. These drugs cross the pla-
main elevated for weeks to months. (6) IgA and IgE sero- centa to the affected fetus. (7) Gastrointestinal symptoms
logic test results will also usually be positive when disease is are the most common adverse effects, but because of the
present. T gondii IgG at birth typically reects maternal risk of bone marrow suppression from the antiprotozoal
antibodies. If a neonate is not infected, specic IgG levels pyrimethamine, twice weekly CBCs are required for the
will return to normal after several months. mother through delivery. The combination of spiramycin
and PSF is not superior to spiramycin monotherapy in pre-
venting vertical transmission (2) and is therefore reserved
Screening
for cases where fetal infection is suspected.
Screening programs exist in many high-incidence countries
Asymptomatic neonates with positive amniocentesis re-
because of the potential severity of congenital infection and
sults, postnatal titers, or clinical symptoms should be pre-
the fact that infected mothers are largely asymptomatic. For
scribed PSF as soon as possible to prevent evolution of
example, in France where the incidence of congenital dis-
neurodevelopmental sequelae. (12) Treatment is contin-
ease is approximately 1 in 1,000 live births, there is a man-
ued at least through the rst year after birth and requires
datory monthly screening program for all seronegative
frequent (12 times per week) laboratory surveillance for
pregnant women. (7) In the United States, Massachusetts
detection of bone marrow suppression and possibly for
and New Hampshire have chosen to include toxoplasma-
hepatitis. (7) Symptomatic infants may be treated longer,
specic IgM titers on their newborn screening panel. (8)
and those with signicant ophthalmologic inammation
The cost-benet ratio of such screening programs in places
may require corticosteroid therapy. (8) Treatment should
with low incidence of disease is a highly debated topic. (7)
be provided in consultation with a toxoplasmosis specialist.
Currently, the United States has no standard prenatal or
At this time, spiramycin is not the favored treatment in
newborn screening recommendations for toxoplasmosis
neonates because it has been associated with QTc prolon-
and practices vary; (9) however, optional prenatal screening
gation and fatal arrhythmias. (13)
is becoming increasingly available.
ACKNOWLEDGMENT. The authors would like to ac-
Treatment knowledge and thank Dr. Joseph R. Hageman, MD,
Because of the evolving strategies and complexity of pre- for his clinical guidance and mentorship in the writing
natal diagnosis, no randomized clinical trials exist to process.
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