Toxoplasmosis Diagnosis, Treatment, Prevention in Congenital Exposed Infants

ARTICLE

Toxoplasmosis: Diagnosis,
Treatment, and Prevention
in Congenitally Exposed
Infants
Alyson Kaye, CPNP, MS, BS

ABSTRACT
Toxoplasmosis is a rare disease caused by the obligate intracellular protozoan parasite, Toxoplasma gondii. Most
persons with toxoplasmosis in the United States are asymptomatic, but if a woman is infected during pregnancy, the parasite can cross the placenta and cause congenital
toxoplasmosis in the fetus. The severity of congenital toxoplasmosis depends on when in the pregnancy the mother is
exposed, but it can cause ocular and central nervous system
disease as well as lead to growth failure and hearing and vision abnormalities. Congenital toxoplasmosis is treated with
a combination of pyrimethamine, sulfadiazine, and leucovorin. It is important for pediatric nurse practitioners to be
aware of the clinical presentation and treatment of congenital
toxoplasmosis. J Pediatr Health Care. (2011) 25, 355-364.

KEY WORDS
Congenital toxoplasmosis, toxoplasmosis, ocular toxoplasmosis, retinochoroiditis, hydrocephalus, pPediatrics, nurse
practitioner, congenital infections, TORCH

The TORCH complex refers to five major congenital
infections that, when contracted by a fetus in utero,
lead to serious and often life-threatening clinical
Alyson Kaye, recent graduate of Columbia University, New York, NY.
Conflicts of interest: None to report.
Correspondence: Alyson Kaye, CPNP, MS, BS, 600 Columbus
Ave, Apt 10M, New York, NY 10024; e-mail: ark2135@columbia.
edu.
0891-5245/$36.00
Copyright Q 2011 by the National Association of Pediatric
Nurse Practitioners. Published by Elsevier Inc. All rights
reserved.
doi:10.1016/j.pedhc.2010.04.008

www.jpedhc.org

sequelae. The ‘‘T’’ in TORCH stands for toxoplasmosis,
an infection by the intracellular parasite Toxoplasma
gondii (Gerber & Hohlfeld, 2003). T. gondii is a member
of the phylum Apicomplexa and parasitic subclass coccidian. The primary host of this parasite is the cat (feline
family), and it is passed through the feces of felines
(Pradhan, Yadav, & Mishra, 2007). Humans can act as
an intermediate host in the parasite’s life cycle. If
a woman is infected while pregnant, this parasite can
cross the placenta from mother to fetus and cause damaging effects to the fetal eye, brain, and other tissues
leading to congenital toxoplasmosis (Gerber &
Hohlfeld, 2003). It is important that pediatric nurse
practitioners (PNPs) be aware of this disease, recognize
when it should be considered as a differential diagnosis,
and understand how it is diagnosed and treated. This article will review the epidemiology, pathophysiology,
transmission, risk factors, clinical presentation, diagnostic methods, and treatment of toxoplasmosis and
will emphasize the role of the nurse practitioner in
clinical education and research.
EPIDEMIOLOGY
The prevalence of toxoplasmosis varies greatly around
the world (Jones, Kruszon-Moran, Sanders-Lewis, &
Wilson, 2007). Prevalence rates are thought to depend
on food production and harvesting practices, water
treatment, environment, climate, and exposure to soil
or sand (Jones et al., 2007). To gather data regarding
the prevalence of this parasite in the United States, serum samples were taken from more than 15,000 volunteers as part of the National Health and Nutrition
Examination Survey between 1999 and 2004 (Jones
et al., 2007). Results of this study demonstrated that
among women of childbearing age (15-44 years), the
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355

prevalence of women with IgG antibodies to T. gondii
born within the United States is 11%. For women born
outside of the United States, the prevalence was higher,
at 28.1% (Jones et al., 2007). The prevalence rates of IgG
antibodies to T. gondii in women of childbearing age
are important to monitor because they provide insight
into the prevalence of congenital toxoplasmosis. No
large-scale studies have examined the prevalence rates
of IgG antibodies to T. gondii in pregnant women, and
toxoplasmosis is not a nationally reported disease
(Lopez, Dietz, Wilson, Navin, & Jones, 2000). According
to the Division of Parasitic Diseases of the National Center for Infectious Diseases, it was estimated in the
United States in the year 2000, 1 in 10,000 live births
results in congenital toxoplasmosis (Brown, Chau,
Atashband, Westerberg, & Kozak, 2009; Lopez et al.,
2000). The incidence of congenital toxoplasmosis is
then estimated to be around 400 to 4000 new cases
every year (Lopez et al., 2000; Pinard, Leslie, & Irvine,
2003).
PATHOPHYSIOLOGY
T. gondii is an obligate intra-cellular protozoan
parasite that is responsible for the disease toxoplasmosis (Tamma & Serwint, 2007). This parasite has a complex life cycle that is relatively host specific and is
divided into three infectious stages (Dubey, 2004;
Kravetz & Federman, 2005). The preferred primary
host for T. gondii is felines (cats), but humans can
become infected when they act as an intermediate
host. When an intermediate host ingests T. gondii,
the first stage, tachyzoites, enter a cell and create
a vacuole to protect themselves from the host’s
immune system (Dubey, 2004). Tachyzoites are resilient and are capable of entering and reproducing in
almost any mammalian or avian cell (Rorman, Zamir,
Rilkis, & Ben-David, 2006). Tachyzoites contained
within certain immune cells can be disseminated
throughout the body until an adequate immune
response is mounted between 7 and 10 days after infection (Kravetz & Federman, 2005). In response to the
host’s immune system, tachyzoites multiply asexually
and produce cysts, each of which contains the next
stage, bradyzoites (Dubey, 2004). Each individual cyst
can contain hundreds of bradyzoites and can be found
within many different types of tissue (Dubey, 2004).
The most common tissues include tissue in the eye,
heart, brain, lungs, liver, and lymph nodes. The intact
cysts can persist for life in a dormant stage in an intermediate host (Kravetz & Federman, 2005). If the immune
system becomes compromised, these bradyzoites can
begin replicating asexually again and will exit the cyst
as tachyzoites and be spread through the body in blood
and lymph systems (Kravetz & Federman, 2005).
When a cat ingests a tissue cyst in meat it consumed,
enzymes in the stomach and intestine degrade the cyst
and bradyzoites are released. Through asexual repro356

Volume 25  Number 6

duction these bradyzoites will become tachyzoites
again, the first aforementioned stage (Dubey, 2004.)
Some bradyzoites will invade the epithelial tissue of
the feline intestine and will begin to multiply through
sexual reproduction to form a fertilized oocyst
(Kravetz & Federman, 2005). These oocysts can only
be formed in the intestine of a wild or domestic member
of the feline family and cannot be formed in an intermediate host such as humans (Dubey, 2004).
Oocysts pass out of the feline host through feces and
become sporulated in the environment, forming the
third stage, sporozoites (Jones, Lopez, & Wilson,
2003). Any host that ingests sporozoites from the environment or acquires tissue cysts from eating infected
meat will become infected with T. gondii (Jones,
Lopez et al., 2003). In humans, contaminated fruit, vegetables, or water that has been in contact with cat feces
is the source of ingestion of sporozoites from the environment. Tissue cysts are usually acquired through the
ingestion of undercooked infected meat (Jones, Lopez
et al., 2003; Pradhan et al., 2007). Bradyzoites released
from an ingested tissue cyst or sporozoites released
from an ingested oocyst penetrate the human
intestine and become tachyzoites again. These
tachyzoites then follow the cycle described previously
(Dubey, 2004).
T. gondii has been shown to be a highly mobile parasite and actively travels through blood and lymph fluid
and across biological barriers such as the intestinal wall,
blood-brain barrier, and the placenta (Rorman et al.,
2006). In humans, the transplacental passage of tachyzoites from mother to fetus leads to congenital toxoplasmosis (Dubey, 2004). In healthy adults, an
infection of T. gondii is asymptomatic in most cases.
The immune system will prevent replication of the parasite and destroy any bradyzoites that are released from
dormant tissue cysts (Dubey, 2004). However, if
a woman is infected during pregnancy, tachyzoites
can cross the placenta and infect the fetus (Dubey,
2004). The symptoms and course of infection depend
on many factors including inoculation factors, virulence of the particular organism, gestational age at
time of infection, sex, genetic factors, and immune
status of the mother and fetus (Pradhan et al., 2007).
The cycle of exposure that leads to congenital toxoplasmosis is illustrated in Figure 1.
VERTICAL TRANSMISSION
Transplacental transmission of T. gondii occurs in approximately 40% of pregnancies in which the mother
is exposed for the first time during the course of the
pregnancy (Bonfioli & Orefice, 2005). In 90% of cases,
the mother will be asymptomatic at the time of infection
(Kravetz & Federman, 2005). It is estimated that 50% of
expectant mothers who give birth to infants congenitally infected with T. gondii have no recollection of
symptoms or any obvious exposure to the parasite
Journal of Pediatric Health Care

FIGURE 1. The cycle of exposure that leads to congenital toxoplasmosis. This figure is available in
color online at www.jpedhc.org.

(Montoya & Remington, 2008). In symptomatic cases,
the mother may experience a range of flu-like symptoms including fever, malaise, and cervical lymphadenopathy (Kravetz & Federman, 2005). Mothers
infected prior to conception rarely transmit the parasite
to the fetus except in cases where the parasite becomes
reactivated because of the immune suppression of the
mother (Jones, Lopez et al., 2003).
In the majority of cases of congenital toxoplasmosis,
the fetus is exposed during the last trimester and symptoms in the infant range from mild to asymptomatic
(Bonfioli & Orefice, 2005). If the fetus is infected during
the first trimester, clinical manifestations are significantly more severe and may result in spontaneous abortion of the fetus. Infection during the second trimester
also may result in a symptomatic infection, but the clinical manifestations vary from mild to severe and depend
on individual factors (Bonfioli & Orefice, 2005; Jones,
Lopez et al., 2003).
RISK FACTORS
The risk factors for T. gondii exposure are directly
related to exposure to cats and more specifically to
cat feces (Box 1). Because cats are the primary host
for T. gondii, cats in the house or stray cats in and
around the house or property are considered a primary
risk factor for acquiring this parasite during pregnancy.
Any job or activity that puts a pregnant woman in direct
contact with soil, sand, or other material that could contain cat feces puts her at risk for being infected
www.jpedhc.org

(Rabinowitz, Gordon, & Odofin, 2007). Drinking water
that has been contaminated by cat feces also can expose
a pregnant woman to T. gondii (Holland, 2003). In the
United States, the majority of cases of congenital toxoplasmosis can be traced back to an exposure to material
containing cat feces or the ingestion of raw food grown
in soil containing cat feces (Safadi, Berezin, Farhat, &
Carvalho, 2003). The ingestion of undercooked or
raw meat during pregnancy is also a risk factor because
the tissue may contain T. gondii cysts that, unless destroyed by cooking heat or food preparation practices,
could infect a pregnant woman (Safadi et al., 2003).
CLINICAL PRESENTATION
Congenitally acquired toxoplasmosis causes a wide
variety of signs and symptoms and typically presents
in one of three ways. In the majority of cases, an infant
BOX 1. Risk factors for contracting
toxoplasmosis
d
d

d
d
d

d

Cats in the home or stray cats in or around the home
Any job or activity that requires contact with dirt, soil, or
other material that could contain cat feces
Ingestion of raw meat, raw eggs, or unpasteurized milk
Drinking untreated water
Touching the eyes or face during or immediately after
food preparation
Ingestion of unwashed fruit or vegetables

November/December 2011

357

will be asymptomatic or have subclinical symptoms at
birth, making the condition difficult to diagnose
(Brown et al., 2009; Safadi et al., 2003). A smaller
minority of infants will present with overt symptoms
in the neonatal period, while the third class of infants
will present with symptoms within the first few weeks
to months of life (Brown et al., 2009).
A PNP should be aware of any red flags in the history
that would allude to the possibility of congenital toxoplasmosis. A history of hydrocephalus, retinochoroiditis, and calcifications in
the central nervous
A history of
system in the newborn
hydrocephalus,
period should immediately alert a care proretinochoroiditis,
vider to the possibility
and calcifications in
of toxoplasmosis. The
the central nervous
signs and symptoms
may be less specific,
system in the
however, and may not
newborn period
be present until later
should immediately
in infancy and childhood (Jones, Lopez
alert a care provider
et al., 2003). These
to the possibility of
symptoms
include
toxoplasmosis.
convulsions, palsies,
growth or mental retardation, visual or hearing impairment, learning disabilities, organomegaly, lymphadenopathy, fever, and
rash (Jones, Lopez et al., 2003). It is important to
remember to place congenital toxoplasmosis on a list
of differential diagnoses for any of the aforementioned
constellation of symptoms. Differential diagnoses for
congenital toxoplasmosis also include other congenital
infections such as cytomegalovirus (CMV), rubella, or
herpes viral infections (Jones, Lopez et al., 2003).
T. gondii can enter cells in the eye of the fetus
through the blood supply of the eye and cause congenital ocular toxoplasmosis. Ocular toxoplasmosis is responsible for up to 17% of cases of uveitis and 25% of
cases of posterior uveitis in the United States
(Soheilian et al., 2005). Ocular effects of toxoplasmosis
can be categorized depending on whether the signs and
symptoms are present in the neonatal period or if they
do not occur until later in life (Bonfioli & Orefice, 2005).
In up to 80% of infants infected with T. gondii who do
not receive treatment, ocular lesions will develop by
the time they reach childhood or early adolescence
(Wallon et al., 2004). The risk of ocular lesions
decreases over time if no lesions are noted in the infant
period (Freeman et al., 2008). Symptoms of ocular toxoplasmosis can vary depending on the age of the patient.
Reduced visual acuity, strabismus, leukocoria, photophobia, pain, and nystagmus are common signs that
should alert a medical provider to the possibility of
toxoplasmosis (Bonfioli & Orefice, 2005; Jedari,
Maliky, & Daneshjou, 2008).
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T. gondii also can invade tissues in the central
nervous system of the developing fetus and can cause
areas of focal and diffuse necrosis in the cerebellum,
cerebrum, spinal cord, and brain stem (Lago,
Baldisserotto, Hoefel Filho, Santiago, & Jungblut,
2007). These areas of necrosis eventually become the
central nervous system calcifications that are characteristic of this disease. It is believed that these areas of calcified tissue are formed from an inadequate amount of
dendritic cells removing necrotic tissue at the affected
sites (Lago et al., 2007). The site of these calcified
lesions varies to some degree by the gestational age at
which a developing fetus is exposed to T. gondii. A fetus exposed before the 20th week of gestation often will
have large dense lesions seen in the basal ganglia (Lago
et al., 2007). A fetus exposed between the 20th and 30th
weeks of gestation typically will present with small
lesions seen in the lateral ventricles. A fetus exposed
after 30 weeks’ gestation may have diffuse lesions in
the cerebral parenchyma (Lago et al., 2007).
It is important that any infant with suspected or confirmed congenital toxoplasmosis receive imaging of the
central nervous system. A computed tomography (CT)
scan and ultrasound are the preferred diagnostic
methods. It is important to use a diagnostic method
that can adequately pick up areas of calcification in
the infant brain (Lago et al., 2007). CT scanning is the
first-line diagnostic method used in North America to
detect central nervous system abnormalities caused
by toxoplasmosis. If concerns exist about the effects
of radiation in the neonatal period, an ultrasound can
be used as an alternative diagnostic method. However,
a negative ultrasound in a patient with confirmed
congenital toxoplasmosis may need to be followed by
a CT scan for confirmation because ultrasound results
can vary depending on the examiner and technology
used (Lago et al., 2007). Therefore, in an infant with
confirmed congenital toxoplasmosis or in an infant
who has symptoms, it may be advisable to order a CT
scan to limit the amount of diagnostic imaging needed.
PHYSICAL ASSESSMENT
Ocular Toxoplasmosis
Toxoplasmosis affects the retina and the underlying
choroid, causing retinochoroiditis, the most common
manifestation of ocular toxoplasmosis (Smith &
Cunningham, 2002). Retinochoroiditis is described as
macular-pigmented lesions with a central necrotic
area primarily found on the retina and can be observed
by funduscopic examination. Retinochoroiditis is illustrated in Figure 2. In more than 50% of cases of ocular
congenital toxoplasmosis, the lesions are found on
the posterior pole of the retina and are unilateral
(Bonfioli & Orefice, 2005). Upon examination of the
eye, a medical provider will see a gray-white area of retinal necrosis with or without exudates with adjacent
swelling of the optic disc, vitreitis, vasculitis, and
Journal of Pediatric Health Care

FIGURE 2. Fundoscopic view of
retinochoroiditis. This figure is available in
color online at www.jpedhc.org.

hemorrhage (Bonfioli & Orefice, 2005; Smith &
Cunningham, 2002). A ‘‘headlight in the fog’’ is
a common description of ocular toxoplasmosis, and it
refers to the retinal inflammation seen through an
infected and opaque vitreous (Bonfioli & Orefice,
2005). Active inflammation and infection in the eye typically lasts about 6 weeks, at which time the lesion will
begin to regress, leaving behind a characteristic pigmented scar on the retina (Smith & Cunningham, 2002).
Ocular toxoplasmosis that is allowed to proceed unchecked without treatment can lead to devastating
long-term effects. It has been associated with glaucoma, cataracts, vitreous opacification, retinal hemorrhage or detachment, and optic atrophy. All of these
conditions can lead to permanent blindness (Bonfioli
& Orefice, 2005). Ocular lesions can recur in adolescence and adulthood, even after treatment in infancy.
Follow-up of these patients is extremely important to
prevent further damage to the eyes (Phan et al., 2008).
Central Nervous System Toxoplasmosis
A congenitally exposed infant with central nervous system calcifications may or may not have overt neurologic
symptoms. Symptoms that have been documented in
infants with congenital toxoplasmosis include convulsions, abnormal tearing of the eye, nystagmus, strabismus, hearing and visual impairments, and growth and
developmental delays (Jones, Lopez et al., 2003).
Many of these symptoms overlap with symptoms of
ocular toxoplasmosis and could be attributed to either
manifestation of this parasitic infection (Jedari et al.,
2008). Toxoplasmosis can also cause hydrocephalus
and microcephaly in the developing fetus (Dimario
et al., 2009).
Sensorineural Hearing Loss and Toxoplasmosis
Toxoplasmosis also has been associated with sensorineural hearing loss. A literature review looking at the
www.jpedhc.org

association between this parasitic infection and hearing
loss found a scarcity of reliable data (Brown et al.,
2009). Only five studies met the inclusion criteria for
the literature review, and they reported such different
results that it is impossible to discern the association
between hearing loss and toxoplasmosis (Brown
et al., 2005). Although the association and cause are
not fully understood at this time, a nurse practitioner
should be aware that the hearing of any child with a history of toxoplasmosis should be evaluated on a regular
basis and that the child should be referred to an audiologist and ear, nose and throat specialist for follow-up
(Brown et al., 2005).
DIAGNOSTIC TESTS
The prevention and treatment of congenital toxoplasmosis begins with identifying infection in pregnant
women. Antibody testing that measures the amount of
IgG and IgM is used to confirm exposure to T. gondii.
IgG and IgM levels rise within 2 weeks of being exposed to the parasite (Jones, Lopez et al., 2003). Elevated IgG levels confirm a patient has been exposed
to the parasite but do not differentiate between a recent
exposure and an exposure that occurred in the past because IgG will persist at a low level throughout the life
of the patient (Jones, Lopez et al., 2003). IgM antibody
levels can be used to confirm an acute exposure, and
the degree of elevation can be used to discern when
the exposure occurred (Lopez et al., 2000). Although
IgM antibodies are almost always present following
an acute exposure, they can persist in some patients
at high levels for up to 18 months, leading to an inaccurate assessment of when the exposure occurred. This
situation can be problematic because congenital toxoplasmosis occurs when the mother is infected during
her pregnancy, and the severity of the disease is determined by ascertaining when in the pregnancy the infection occurred (Nascimento, Suzuki, & Rossi, 2008). A
significant increase in specific antibody titers or seroconversion during pregnancy is usually considered diagnostic of a recent exposure (Nascimento et al., 2008).
Despite serologic evidence demonstrating the likelihood of recent exposure, a T. gondii reference laboratory must confirm the diagnosis, in part because of
questions about the sensitivity and specificity of IgG
and IgM antibody testing (Tamma & Serwint, 2007).
The Sabin Feldman Dye test is performed by a reference
laboratory and is considered the gold-standard diagnostic test for toxoplasmosis. This test detects a change
in T. gondii–specific antibody titers (IgG) over a 3-week
period or detects a single elevated (IgG) antibody titer
(Rorman et al., 2006). A four-fold increase in titer levels
over a three-week period or a single titer above 250 IU/
ml is considered highly suggestive of infection (Rorman
et al., 2006). Polymerase chain reaction testing of amniotic fluid is the preferred method for providing confirmation of fetal exposure (Jones, Lopez et al., 2003).
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Volume 25  Number 6

Palpitations, chest pain, QT
prolongation, diarrhea, nausea, rash,
ototoxicity, hypersensitivity
Consult infectious disease specialist

Consult infectious disease specialist
Inhibits protein synthesis

Inhibits protein synthesis
Azithromycin

*Standard of care.

Inhibits dihydrofolic acid synthesis

Trimethoprim
sulfamethoxazole
Clindamycin

No standard dose; dose is based on
weight and postnatal age; consult
infectious disease specialist
for dosing
Consult infectious disease specialist

First 6 months
Second 6 months
Consult infectious disease specialist
5-10 mg every 3 days
10 mg three times per week
Consult infectious disease specialist
A reduced form of folic acid
Folinic acid (leucovorin)*

Inhibits tetrahydrofolic acid synthesis
Pyrimethamine*

1 mg/kg/day
1 mg/kg/day three times per week

First 6 months
Second 6 months

Bone marrow suppression, fever,
vasculitis, rash, nausea, vomiting,
nephropathy
Bone marrow suppression, rash,
seizures, fever, vomiting, diarrhea,
hematuria
Rash, erythema, urticaria, wheezing,
thrombocytosis, hypersensitivity
Bone marrow suppression,
hypotension, rash, seizures, fever
Pseudomembranous colitis,
hypotension, cardiac arrhythmia,
rash, bone marrow suppression
Inhibits folic acid synthesis
Sulfadiazine*

100 mg/kg/day divided every 12 hours

1 year

Length of therapy
Dose
Mechanism of action
Medication

TABLE. Medications used to treat toxoplasmosis

TREATMENT
Standard of Care
The goal of initiating treatment is to arrest the replication
of the parasite and prevent further damage to the organs
involved. It is especially important to stop replication in
the eye to prevent irreversible damage to the retina and
optic nerve that can lead to permanent blindness
(Soheilian et al., 2005).
Currently, The World
The goal of initiating
Health Organization
treatment is to
and the Centers for Disease Control and Prearrest the
vention recommend
replication of the
pyrimethamine, sulfaparasite and
diazine, and leucovorin
as the standard of
prevent further
care for persons with
damage to the
congenital toxoplasorgans involved.
mosis (Rorman et al.,
2006). These medications were proven to be effective in a randomized prospective study called the National Collaborative
Chicago Based Congenital Toxoplasmosis Study
(NCCBTS). This study found that treatment with the
three aforementioned medications significantly decreased adverse signs and symptoms associated with
congenital toxoplasmosis, including ocular and central
nervous system symptoms and sensorineural hearing
loss (McLeod et al., 2006). This combination of medications also is recommended by the American Academy
of Pediatrics (AAP). For patients with sensitivity to sulfadiazine, clindamycin can be used in combination with
pyrimethamine as an alternative (AAP, 2009). Information regarding these medications and other alternative
medications that could be used to treat toxoplasmosis
can be found in the Table (Soheilian et al, 2005;
Taketomo, Hodding, & Kraus, 2008). A provider also
may add a corticosteroid to decrease the inflammation
caused by the replication of the parasite and to
manage the associated ocular complications (AAP,
2009; Soheilian et al., 2005).
Both pyrimethamine and sulfadiazine act by inhibiting folic acid synthesis in T. gondii. By using different
mechanisms of action, they complement one another
to create a combined effect (Schmidt et al., 2006).
Although they have been proven effective, they do not
come without serious adverse effects and should never
be prescribed without diagnostic confirmation of toxoplasmosis (Schmidt et al., 2006). As previously stated,

Adverse effects

This test should be performed at or after 18 weeks’ gestation and only in women with preliminary positive
serologic results indicative of acute exposure
(Montoya & Remington, 2008). Polymerase chain reaction testing of cerebrospinal fluid also can be used to
confirm the presence of infection in the central nervous
system after birth (Tamma & Serwint, 2007).

Journal of Pediatric Health Care

pyrimethamine decreases the synthesis of folic acid both
in T. gondii and in its human host. Thus a major adverse
effect of this treatment regimen is bone marrow suppression (Schmidt et al., 2006). Bone marrow suppression
leads to neutropenia, anemia, and thrombocytopenia.
This adverse effect may be avoided with the simultaneous administration of folic acid during treatment
(Schmidt et al., 2006; Soheilian et al., 2005).
Leucovorin, a folic acid derivative, also can be used to
combat myelosuppression and is given concurrently
with pyrimethamine and sulfadiazine (Jones, Lopez
et al., 2003). Despite these preventative measures,
weekly monitoring of cell counts and platelet counts
should be done to assess the level of marrow suppression and adjust these medications as necessary
(Soheilian et al., 2005).
At this time, debate exists about the appropriate length
of therapy. Some studies that argue in some patients, 3
months of therapy may be sufficient to eradicate the
parasite and prevent long-term effects as well as decrease
the burden of long-term medication usage on the
affected infant and family (Freeman et al., 2008). However, most treatment recommendations suggest that decisions concerning whether therapy should be continued
or discontinued be based on patient response to therapy
as well as the severity of symptoms and the age of the patient at the time of diagnosis (Schmidt et al., 2006). Results
from the NCCBTS study and the AAP recommend treatment of pyrimethamine, sulfadiazine, and folic acid
(leucovorin) for a prolonged period, often up to 1 year
(AAP, 2009; McLeod et al., 2006). At this time there
is still debate regarding dosages and length of therapy,
and thus a specialist in infectious disease and
toxoplasmosis should be consulted prior to treatment
initiation or treatment discontinuation (AAP, 2009).
Treatment for Expectant Mothers
Treatment of a woman during pregnancy also has been
studied to prevent congenital toxoplasmosis. During
the first trimester of pregnancy, pyrimethamine is contraindicated because of the teratogenic effects of this
medication. Sulfadiazine may be used alone during
the first trimester and pyrimethamine may be added
to the regimen after this crucial period of fetal development if the benefit of this drug outweighs the risk to the
fetus (Freeman et al., 2008). Although not yet approved
by the Food and Drug Administration in the United
States, another medication called spiramycin is used
to prevent transplacental infection in many other countries. Spiramycin is available in the United States under
special circumstances as an investigational medication
(Rorman et al., 2006).
Overall, the research pertaining to anti-toxoplasmic
treatment is lacking. The majority of studies are retrospective, and few randomized control trials exist that
look at medication efficacy. More research must be
done in this area to develop the best treatment for
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pregnant women and neonates congenitally exposed
to T. gondii.
NEONATAL SCREENING
Screening for toxoplasmosis is a controversial topic. In
populations with a low prevalence, screening of pregnant mothers is not believed to be cost-effective, nor
is treatment during pregnancy guaranteed to prevent
congenital toxoplasmosis (Dimario et al., 2009).
Screening in the neonatal period may be a more feasible
option for primary care providers (Jara, Hsu, Eaton, &
Demaria, 2001). In 1986, Massachusetts added toxoplasmosis to its newborn screening and created
follow-up recommendations for infants with positive
serologic findings (Jara et al., 2001). Currently in the
United States, Massachusetts and New Hampshire are
the only two states that routinely screen for toxoplasmosis at birth. IgM and IgG antibody testing is used to
screen all infants in these two states at the same time
that all other newborn screening is conducted (Jara
et al., 2001). It is important to note that positive serologic results demonstrate that the mother has been
exposed and do not definitively indicate congenital
toxoplasmosis in the infant (Jara et al., 2001). The
results simply allow the primary care provider to be
aware of the possibility and provide further follow-up
as indicated.
Preliminary data from these two states suggest that
the prevalence of congenital toxoplasmosis is 1 in
12,000 live births and that providing treatment to
these infants early in life significantly decreases the
neurologic and ophthalmologic effects of this disease
(Jara et al., 2001). Between 1986 and 1992, 52 infants
in Massachusetts and New Hampshire were identified
as having been congenitally infected. Fifty of these infants were identified through neonatal screening alone,
and after 1 year of treatment, only one infant demonstrated a neurologic deficit and four infants demonstrated lesions in the eye (Lopez et al., 2000). Thus
these preliminary data demonstrate that early screening
and treatment can significantly decrease the long-term
sequelae of congenital toxoplasmosis. Neonatal
screening has limitations, however, and should never
be used as diagnostic confirmation of congenital toxoplasmosis because the sensitivity and specificity of such
testing, especially using filtered blood samples, is low
and could provide false results (Dimario et al., 2009).
ROLE OF THE NURSE PRACTITIONER
Implications for Clinical Practice
PNPs play an important role in recognizing and treating
congenital toxoplasmosis. Because screening for toxoplasmosis does not always occur during the prenatal
period, many prenatal infections go unnoticed and undocumented. A mother may be unaware that she has
been exposed to the parasite and unaware of the risks
that T. gondii can pose to her infant. The first step for
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361

BOX 2. Important screening questions for
Toxoplasma gondii seronegative expectant
mothers to assess the risk of T. gondii
exposure
Questions
d
d

d
d

d
d

d

Do you own a cat?
If you own a cat, does your cat go outdoors or hunt and
eat raw meat?
Do you garden?
Do you work or participate in any activity where you are
directly exposed to sand, dirt, or soil?
Do you eat meat? If yes, how is it prepared?
Do you eat raw fruit and vegetables? If yes, how are they
prepared?
Have you traveled to any foreign countries? If yes, where
and what did you eat, and did you drink the water?

Based on the answers to these questions, a practitioner
can provide the necessary education to prevent exposure.

all PNPs in primary care is to be aware of this infection
and to ask each new mother about her possible exposure to the organism. Important screening questions
presented in Box 2 should be asked at newborn visits
and any prenatal visits. These questions can provide
an idea of the level of risk and whether congenital toxoplasmosis is a possibility, especially if any abnormalities
are noted in the newborn.
An infant that has been congenitally exposed to
T. gondii will require medical care, monitoring, and
follow-up throughout infancy, childhood, and adolescence. A PNP can provide a medical home and can
coordinate primary care with specialty care including
ophthalmology, neurology, audiology, and infectious
disease specialists, depending on the clinical needs of
the patient. Although treatment during infancy can
decease the long-term effects of congenital toxoplasmosis, children and adolescents who were treated in infancy are still at risk for ocular complications later in life.
Because of this risk, it is important to ensure that
patients receive routine ophthalmologic monitoring to
identify ocular complications before they lead to
permanent damage of the eye (Phan et al., 2008).
Patient Education
In the United States it is estimated that 85% of pregnant
women have never been exposed to T. gondii and thus
are at risk for contracting the parasite during pregnancy
(Jones, Ogunmodede et al., 2003). Prevention of congenital toxoplasmosis begins with preventing primary
infection. Despite the fact that T. gondii can be avoided
by implementing relatively simple strategies in daily
life, the majority of pregnant women are unaware of
how to prevent exposure (Jones, Ogunmodede et al.,
2003). A survey of 400 pregnant women in the United
States demonstrated that only half were aware of
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Volume 25  Number 6

toxoplasmosis. Most of these women knew toxoplasmosis was associated with cat litter but were unsure
as to why and did not know about exposure in the
environment through food, water, dirt, sand, or soil
(Jones, Ogunmodede et al., 2003).
Sporulated oocysts can be found in dirt, sand, or soil
and on the skins of raw fruits and vegetables grown in
these substrates (Lopez et al., 2000). Limiting contact
with dirt, sand, or soil can help prevent the ingestion
of oocysts from the environment, and if contact occurs,
an expectant mother should be taught to thoroughly
wash her hands to avoid ingesting the parasite
(Dimario et al., 2009; Lopez et al., 2000). Wearing
gloves while gardening, for example, also can limit the
contact a pregnant woman may have with these
environmental hazards (Pinard et al., 2003). The skins
of all raw fruit and vegetables should be washed and
then peeled away because oocysts may be attached to
these parts of the food and could be ingested. Again,
hand washing should be strongly emphasized after handling any raw food including fruits, vegetables, and
meat products (Lopez et al., 2000). T. gondii cysts can reside in the meat of many different types of mammals or
birds. In the United States, it is estimated that 8% of beef
and 20% of lamb and pork meat contains T. gondii tissue
cysts (Kravetz & Federman, 2005). All pregnant women
should be taught to never ingest raw meat and to cook
all meat to an internal temperature of at least 152°F to
destroy the tissue cysts (Kravetz & Federman, 2005).
Because cats are the primary host for T. gondii, it is important that pregnant women be aware of the risks they
may pose. Contact with cat litter should be avoided if
possible, and if contact
is unavoidable, gloves
Because cats are
should be worn while
the primary host for
changing the litter box
and hands should be
T. gondii, it is
washed thoroughly afimportant that
terward (Lopez et al.,
pregnant women
2000; Pinard et al.,
2003). Frequent litter
be aware of the
changes should be
risks they may
done because it takes
pose.
several
days
for
oocysts to become
infectious, and the box should be thoroughly cleaned with disinfecting agents (Lopez et al.,
2000; Pinard et al., 2003). Preventing a cat from
hunting outdoors or eating raw meat also can prevent
the feline from being infected with T. gondii.
Practitioners should encourage pregnant women to
keep indoor-only cats and to feed them only canned
or dry food that has been bought in a store (Lopez
et al., 2000).
Providing education to expectant mothers is an important part of the provision of primary care for PNPs.
A practitioner should provide materials and information
Journal of Pediatric Health Care

FIGURE 3. An example of a handout that could be given to expectant mothers. This figure is available
in color online at www.jpedhc.org.

in a variety of languages and use common language instead of medical jargon to teach important points to patients. Handouts that are culturally sensitive and
appropriate for mothers with low literacy skills or who
cannot read should be used (Montoya & Remington,
2008). Using pictures and color demonstrations of
hand washing, cooking, and wearing gloves may be
helpful when teaching about toxoplasmosis if translation into another language is difficult (Montoya &
Remington, 2008). In addition, creating handouts that
a patient can simply hang in the home as a quick reminder may be useful. Figure 3 is an example of a handout for expectant mothers. Although research that looks
at the role of prenatal education in preventing congenital toxoplasmosis is limited, current recommendations
suggest that all pregnant women be given information
through written materials and discussions with medical
providers (Dimario et al., 2009). PNPs play an important
role in providing this information to their patients and to
expectant mothers.
www.jpedhc.org

CONCLUSION
PNPs play an active role in the primary care of infants. A
PNP may be the first medical provider who sees a newborn after he or she is released from the hospital and
can provide primary care throughout infancy and childhood. It is important that PNPs be able to recognize and
diagnose congenital toxoplasmosis as well as provide
and coordinate treatment and long-term follow-up
care for these patients.
The author wishes to thank Dr. Rita Marie John,
CPNP, DNP, EdD, Columbia University School of
Nursing, for her guidance and review of this article.
REFERENCES
American Academy of Pediatrics. (2009). Summaries of infectious
diseases. In L. K. Pickering, C. J. Baker, D. W. Kimberlin &
S. S. Long (Eds.), Red Book: 2009 report of the Committee
on Infectious Diseases (28th ed.). Elk Grove Village, IL: Author.
Bonfioli, A. A., & Orefice, F. (2005). Toxoplasmosis. Seminars in
Ophthalmology, 20(3), 129-141.

November/December 2011

363

Brown, E. D., Chau, J. K., Atashband, S., Westerberg, B. D., &
Kozak, F. K. (2009). A systematic review of neonatal toxoplasmosis exposure and sensorineural hearing loss. International
Journal of Pediatric Otorhinolaryngology, 73(5), 707-711.
Dimario, S., Basevi, V., Gagliotti, C., Spettoli, D., Gori, G., D’Amico, R.,
. Magrini, N. (2009). Prenatal education for congenital
toxoplasmosis. Cochrane Database of Systematic Reviews, 2,
1-18.
Dubey, J. P. (2004). Toxoplasmosis: A waterborne zoonosis. Veterinary Parasitology, 126, 57-72.
Freeman, K., Tan, H. K., Prusa, A., Peterson, E., Buffolano, W.,
Malm, G., . Gilbert, R. (2008). Predictors of retinochoroiditis
in children with congenital toxoplasmosis: European prospective cohort study. Pediatrics, 121(5), 1215-1222.
Gerber, S., & Hohlfeld, P. (2003). Screening for infectious diseases.
Child’s Nervous System, 19, 492-432.
Holland, G. N. (2003). Ocular toxoplasmosis: A global reassessment.
Part 1: Epidemiology and course of disease. American Journal
of Ophthalmology, 136(6), 973-988.
Jara, M., Hsu, H. W., Eaton, R., & Demaria, A. (2001). Epidemiology
of congenital toxoplasmosis identified by population-based
newborn screening in Massachusetts. The Pediatric Infectious
Disease Journal, 20(12), 1132-1135.
Jedari, A. S., Maliky, Z., & Daneshjou, K. (2008). A 10 month old with
nystagmus and strabismus. Pakistan Journal of Biological
Sciences, 11(5), 817-818.
Jones, J. L., Lopez, A., & Wilson, M. (2003). Congenital toxoplasmosis. American Family Physician, 67(10), 2131-2138.
Jones, J. L., Kruszon-Moran, D., Sanders-Lewis, K., & Wilson, M.
(2007). Toxoplasma gondii infection in the United States,
1999-2004, Decline from the prior decade. The American
Journal of Tropical Medicine and Hygiene, 77(3), 405-410.
Jones, J. L., Ogunmodede, F., Scheftel, J., Kirkland, E., Lopez, A.,
Schulkin, J., . Lynfield, R. (2003). Toxoplasmosis related
knowledge and practices among pregnant women in the United
States. Infectious Diseases in Obstetrics and Gynecology,
11(3), 139-145.
Kravetz, J. D., & Federman, D. G. (2005). Toxoplasmosis in pregnancy. The American Journal of Medicine, 118(3), 212-216.
Lago, E. G., Baldisserotto, M., Hoefel Filho, J. R., Santiago, D., &
Jungblut, R. (2007). Agreement between ultrasonography
and computed tomography in detecting intracranial calcifications in congenital toxoplasmosis. Clinical Radiology, 62(10),
1004-1011.
Lopez, A., Dietz, V. J., Wilson, M., Navin, T. R., & Jones, J. L. (2000).
Preventing congenital toxoplasmosis. MMWR Recommendations and Reports, 49(2), 59-68.
McLeod, R., Boyer, K., Karrison, T., Kasza, K., Swisher, C., Roizen, N.,
. Meier, P. (2006). Outcome of treatment for congenital Toxoplasmosis, 1981-2004: The National Collaborative Chicago-

364

Volume 25  Number 6

Based, Congenital Toxoplasmosis Study. Clinical Infectious
Diseases, 42(10), 1383-1394.
Montoya, J. G., & Remington, J. S. (2008). Management of
Toxoplasma gondii infection during pregnancy. Clinical Infectious Diseases, 47(4), 554-566.
Nascimento, F. S., Suzuki, L. A., & Rossi, C. L. (2008). Assessment of
the value of detecting specific IgA antibodies for the diagnosis of
a recently acquired primary Toxoplasma infection. Prenatal
Diagnosis, 28(8), 749-752.
Phan, L., Kasza, K., Jalbrzikowski, J., Noble, A. G., Latkany, P.,
Kuo, A., . McLeod, R. (2008). Longitudinal study of new
eye lesions in treated congenital toxoplasmosis. American
Journal of Ophthalmology, 115(3), 553-559.
Pinard, J. A., Leslie, N. S., & Irvine, P. J. (2003). Maternal serologic
screening for toxoplasmosis. Journal of Midwifery and
Women’s Health, 48(5), 308-316.
Pradhan, S., Yadav, R., & Mishra, V. N. (2007). Toxoplasma meningoencephalitis in HIV-seronegative patients: Clinical patterns,
imaging features and treatment outcome. Transactions of the
Royal Society of Tropical Medicine and Hygiene, 101(1), 25-33.
Rabinowitz, P. M., Gordon, Z., & Odofin, L. (2007). Pet related
infections. American Family Physician, 76(9), 1314-1322.
Rorman, E., Zamir, C. S., Rilkis, I., & Ben-David, H. (2006). Congenital toxoplasmosis-prenatal aspects of toxoplasma gondii
infection. Reproductive Toxicology, 21(4), 458-472.
Safadi, M. A., Berezin, E. N., Farhat, C. K., & Carvalho, E. S. (2003).
Clinical presentation and follow-up of children with congenital
toxoplasmosis in Brazil. The Brazilian Journal of Infectious
Diseases, 7(5), 325-331.
Schmidt, D. R., Hogh, B., Anderson, O., Hansen, S. H., Dalhoff, K., &
Peterson, E. (2006). Treatment of infants with congenital toxoplasmosis: Tolerability and plasma concentrations of sulfadiazine and pyrimethamine. European Journal of Pediatrics,
165(1), 19-25.
Smith, J. R., & Cunningham, E. T. (2002). Atypical presentations of
ocular toxoplasmosis. Current Opinions in Ophthalmology,
13(6), 387-392.
Soheilian, M., Sadoughi, M., Ghajarnia, M., Dehghan, M., Yazdani, S.,
Behboudi, H., . Peyman, G. A. (2005). Prospective randomized
trial of trimethoprim/sulfamethoxazole versus pyrimethamine and
sulfadiazine in the treatment of ocular toxoplasmosis. Ophthalmology, 112(11), 1876-1882.
Tamma, P., & Serwint, J. R. (2007). Toxoplasmosis. Pediatrics, 28,
470-471.
Taketomo, C. K., Hodding, J. H., & Kraus, D. M. (2008). Pediatric
dosage handbook (15th ed.). Hudson, OH: Lexi-Comp Inc.
Wallon, M., Kodjikian, L., Binquet, C., Garweg, J., Fleury, J.,
Quantin, C., . Peyron, F. (2004). Long-term ocular prognosis
in 327 children with congenital toxoplasmosis. Pediatrics,
113(6), 1567-1572.

Journal of Pediatric Health Care