ARTICLE

Toxoplasmosis: DTreatment, and Pin Congenitally E

ABSTRACT

KEY WORDSCongenital toxoplasmosis, toxoplasmosis, ocular toxoplas-mosis, retinochoroiditis, hydrocephalus, pPediatrics, nurse

andunderstandhow it is diagnosedand treated. This ar-ticle will review the epidemiology, pathophysiology,transmission, risk factors, clinical presentation, diag-

mosis andtitioner in

clinical education and research.

tly around-Lewis, &to dependces, waterure to soilregardingStates, se-000 volun-Nutrition04 (Jonestrated that

among women of childbearing age (15-44 years), thedoi:10.1016/j.pedhc.2010.04.008www.jpedhc.org November/December 2011 355The TORCH complex refers to five major congenitalinfections that, when contracted by a fetus in utero,lead to serious and often life-threatening clinical EPIDEMIOLOGY

The prevalence of toxoplasmosis varies greathe world (Jones, Kruszon-Moran, SandersWilson, 2007). Prevalence rates are thoughton food production and harvesting practitreatment, environment, climate, and exposor sand (Jones et al., 2007). To gather datathe prevalence of this parasite in the Unitedrum samples were taken from more than 15,teers as part of the National Health andExamination Survey between 1999 and 20et al., 2007). Results of this study demons

AlysonKaye, recentgraduateofColumbiaUniversity,NewYork,NY.

Conflicts of interest: None to report.

Correspondence: Alyson Kaye, CPNP, MS, BS, 600 ColumbusAve, 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.practitioner, congenital infections, TORCH nostic methods, and treatment of toxoplaswill emphasize the role of the nurse pracToxoplasmosis is a rare disease caused by the obligate intra-cellular protozoan parasite, Toxoplasma gondii. Mostpersons with toxoplasmosis in the United States are asymp-tomatic, but if a woman is infected during pregnancy, the par-asite can cross the placenta and cause congenitaltoxoplasmosis in the fetus. The severity of congenital toxo-plasmosis depends on when in the pregnancy the mother isexposed, but it can cause ocular and central nervous systemdisease as well as lead to growth failure and hearing and vi-sion abnormalities. Congenital toxoplasmosis is treated witha combination of pyrimethamine, sulfadiazine, and leuco-vorin. It is important for pediatric nurse practitioners to beaware of the clinical presentation and treatment of congenitaltoxoplasmosis. J Pediatr Health Care. (2011) 25, 355-364.Alyson Kaye, CPNP, MS, BSInfantssequelae. The T in TORCH stands for toxoplasmosis,an infection by the intracellular parasite Toxoplasmagondii (Gerber&Hohlfeld, 2003).T. gondii is amemberof the phylum Apicomplexa and parasitic subclass coc-cidian. The primary host of this parasite is the cat (felinefamily), and it is passed through the feces of felines(Pradhan, Yadav, & Mishra, 2007). Humans can act asan intermediate host in the parasites life cycle. Ifa woman is infected while pregnant, this parasite cancross the placenta frommother to fetus and cause dam-aging effects to the fetal eye, brain, and other tissuesleading to congenital toxoplasmosis (Gerber &Hohlfeld, 2003). It is important that pediatric nursepractitioners (PNPs) be aware of this disease, recognizewhen it should be considered as adifferential diagnosis,iagnosis,reventionxposed

prevalence of women with IgG antibodies to T. gondiiborn within the United States is 11%. For women bornoutside of the United States, the prevalencewas higher,at 28.1% (Jones et al., 2007). The prevalence rates of IgGantibodies to T. gondii in women of childbearing ageare important to monitor because they provide insightinto the prevalence of congenital toxoplasmosis. Nolarge-scale studies have examined the prevalence ratesof IgG antibodies to T. gondii in pregnant women, andtoxoplasmosis is not a nationally reported disease(Lopez,Dietz,Wilson,Navin,& Jones, 2000). Accordingto theDivision of Parasitic Diseases of theNational Cen-ter for Infectious Diseases, it was estimated in theUnited States in the year 2000, 1 in 10,000 live birthsresults in congenital toxoplasmosis (Brown, Chau,Atashband, Westerberg, & Kozak, 2009; Lopez et al.,2000). The incidence of congenital toxoplasmosis isthen estimated to be around 400 to 4000 new casesevery year (Lopez et al., 2000; Pinard, Leslie, & Irvine,2003).

PATHOPHYSIOLOGYT. gondii is an obligate intra-cellular protozoanparasite that is responsible for the disease toxoplasmo-sis (Tamma & Serwint, 2007). This parasite has a com-plex life cycle that is relatively host specific and isdivided into three infectious stages (Dubey, 2004;Kravetz & Federman, 2005). The preferred primaryhost for T. gondii is felines (cats), but humans canbecome infected when they act as an intermediatehost. When an intermediate host ingests T. gondii,the first stage, tachyzoites, enter a cell and createa vacuole to protect themselves from the hostsimmune system (Dubey, 2004). Tachyzoites are resil-ient and are capable of entering and reproducing inalmost any mammalian or avian cell (Rorman, Zamir,Rilkis, & Ben-David, 2006). Tachyzoites containedwithin certain immune cells can be disseminatedthroughout the body until an adequate immuneresponse is mounted between 7 and 10 days after infec-tion (Kravetz & Federman, 2005). In response to thehosts immune system, tachyzoites multiply asexuallyand produce cysts, each of which contains the nextstage, bradyzoites (Dubey, 2004). Each individual cystcan contain hundreds of bradyzoites and can be foundwithin many different types of tissue (Dubey, 2004).The most common tissues include tissue in the eye,heart, brain, lungs, liver, and lymph nodes. The intactcysts canpersist for life in adormant stage in an interme-diate host (Kravetz & Federman, 2005). If the immunesystem becomes compromised, these bradyzoites canbegin replicating asexually again and will exit the cystas tachyzoites and be spread through the body in bloodand lymph systems (Kravetz & Federman, 2005).When a cat ingests a tissue cyst in meat it consumed,

enzymes in the stomach and intestine degrade the cystand bradyzoites are released. Through asexual repro-356 Volume 25 Number 6duction these bradyzoites will become tachyzoitesagain, the first aforementioned stage (Dubey, 2004.)Some bradyzoites will invade the epithelial tissue ofthe feline intestine and will begin to multiply throughsexual reproduction to form a fertilized oocyst(Kravetz & Federman, 2005). These oocysts can onlybe formed in the intestine of awild or domesticmemberof the feline family and cannot be formed in an interme-diate host such as humans (Dubey, 2004).Oocysts pass out of the feline host through feces and

become sporulated in the environment, forming thethird stage, sporozoites (Jones, Lopez, & Wilson,2003). Any host that ingests sporozoites from the envi-ronment or acquires tissue cysts from eating infectedmeat will become infected with T. gondii (Jones,Lopez et al., 2003). In humans, contaminated fruit, veg-etables, or water that has been in contact with cat fecesis the source of ingestion of sporozoites from the envi-ronment. Tissue cysts are usually acquired through theingestion of undercooked infected meat (Jones, Lopezet al., 2003; Pradhan et al., 2007). Bradyzoites releasedfrom an ingested tissue cyst or sporozoites releasedfrom an ingested oocyst penetrate the humanintestine and become tachyzoites again. Thesetachyzoites then follow the cycle described previously(Dubey, 2004).T. gondii has been shown to be a highly mobile par-

asite and actively travels through blood and lymph fluidand across biological barriers such as the intestinalwall,blood-brain barrier, and the placenta (Rorman et al.,2006). In humans, the transplacental passage of tachy-zoites from mother to fetus leads to congenital toxo-plasmosis (Dubey, 2004). In healthy adults, aninfection of T. gondii is asymptomatic in most cases.The immune system will prevent replication of the par-asite and destroy any bradyzoites that are released fromdormant tissue cysts (Dubey, 2004). However, ifa woman is infected during pregnancy, tachyzoitescan cross the placenta and infect the fetus (Dubey,2004). The symptoms and course of infection dependon many factors including inoculation factors, viru-lence of the particular organism, gestational age attime of infection, sex, genetic factors, and immunestatus of the mother and fetus (Pradhan et al., 2007).The cycle of exposure that leads to congenital toxoplas-mosis is illustrated in Figure 1.

VERTICAL TRANSMISSIONTransplacental transmission of T. gondii occurs in ap-proximately 40% of pregnancies in which the motheris exposed for the first time during the course of thepregnancy (Bonfioli & Orefice, 2005). In 90% of cases,themotherwill be asymptomatic at the time of infection(Kravetz & Federman, 2005). It is estimated that 50% ofexpectant mothers who give birth to infants congeni-tally infected with T. gondii have no recollection ofsymptoms or any obvious exposure to the parasiteJournal of Pediatric Health Care

ongenital toxoplasmosis. This figure is available in(Montoya & Remington, 2008). In symptomatic cases,the mother may experience a range of flu-like symp-toms including fever, malaise, and cervical lymphade-nopathy (Kravetz & Federman, 2005). Mothers

FIGURE 1. The cycle of exposure that leads to ccolor online at www.jpedhc.org.infected prior to conception rarely transmit the parasiteto the fetus except in cases where the parasite becomesreactivated because of the immune suppression of themother (Jones, Lopez et al., 2003).In the majority of cases of congenital toxoplasmosis,

the fetus is exposed during the last trimester and symp-toms in the infant range from mild to asymptomatic(Bonfioli &Orefice, 2005). If the fetus is infected duringthe first trimester, clinical manifestations are signifi-cantlymore severe andmay result in spontaneous abor-tion of the fetus. Infection during the second trimesteralso may result in a symptomatic infection, but the clin-icalmanifestations vary frommild to severe anddependon individual factors (Bonfioli & Orefice, 2005; Jones,Lopez et al., 2003).

RISK FACTORSThe risk factors for T. gondii exposure are directlyrelated to exposure to cats and more specifically tocat feces (Box 1). Because cats are the primary hostfor T. gondii, cats in the house or stray cats in andaround the house or property are considered a primaryrisk factor for acquiring this parasite during pregnancy.Any job or activity that puts a pregnant woman in directcontact with soil, sand, or other material that could con-tain cat feces puts her at risk for being infected

www.jpedhc.org(Rabinowitz, Gordon, & Odofin, 2007). Drinking waterthat has been contaminatedby cat feces also can exposea pregnant woman to T. gondii (Holland, 2003). In theUnited States, the majority of cases of congenital toxo-

plasmosis can be traced back to an exposure tomaterialcontaining cat feces or the ingestion of raw food grownin soil containing cat feces (Safadi, Berezin, Farhat, &Carvalho, 2003). The ingestion of undercooked orrawmeat during pregnancy is also a risk factor becausethe tissue may contain T. gondii cysts that, unless de-stroyed by cooking heat or food preparation practices,could infect a pregnant woman (Safadi et al., 2003).

CLINICAL PRESENTATIONCongenitally acquired toxoplasmosis causes a widevariety of signs and symptoms and typically presentsin one of three ways. In the majority of cases, an infant

BOX 1. Risk factors for contractingtoxoplasmosis

d Cats in the home or stray cats in or around the homed Any job or activity that requires contact with dirt, soil, orother material that could contain cat feces

d Ingestion of raw meat, raw eggs, or unpasteurized milkd Drinking untreated waterd Touching the eyes or face during or immediately afterfood preparation

d Ingestion of unwashed fruit or vegetables

November/December 2011 357

for any of the aforementionedms. Differential diagnoses foris also include other congenitalegalovirus (CMV), rubella, orones, Lopez et al., 2003).cells in the eye of the fetusy of the eye and cause congen-is. Ocular toxoplasmosis is re-of cases of uveitis and 25% ofveitis in the United Statescular effects of toxoplasmosis

ndingonwhether the signs andthe neonatal period or if theylife (Bonfioli &Orefice, 2005).nfected with T. gondii who docular lesions will develop bythe time they reach childhood or early adolescence(Wallon et al., 2004). The risk of ocular lesionsdecreases over time if no lesions are noted in the infantperiod (Freemanet al., 2008). Symptoms of ocular toxo-plasmosis can vary depending on the age of the patient.Reduced visual acuity, strabismus, leukocoria, photo-phobia, pain, and nystagmus are common signs thatshould alert a medical provider to the possibility oftoxoplasmosis (Bonfioli & Orefice, 2005; Jedari,Maliky, & Daneshjou, 2008).remember to place conof differential diagnosesconstellation of symptocongenital toxoplasmosinfections such as cytomherpes viral infections (JT. gondii can enter

through the blood supplital ocular toxoplasmossponsible for up to 17%cases of posterior u(Soheilian et al., 2005). Ocanbe categorizeddepesymptoms are present indo not occur until later inIn up to 80% of infants inot receive treatment, owill be asymptomatic or have subclinical symptoms atbirth, making the condition difficult to diagnose(Brown et al., 2009; Safadi et al., 2003). A smallerminority of infants will present with overt symptomsin the neonatal period, while the third class of infantswill present with symptoms within the first few weeksto 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 toxo-plasmosis. A history of hydrocephalus, retinochoroidi-tis, and calcifications inthe central nervoussystem in the newbornperiod should immedi-ately alert a care pro-vider to the possibilityof toxoplasmosis. Thesigns and symptomsmay be less specific,however, and may notbe present until laterin infancy and child-hood (Jones, Lopezet al., 2003). Thesesymptoms includeconvulsions, palsies,growth or mental retar-dation, visual or hearing impairment, learning disabil-ities, organomegaly, lymphadenopathy, fever, andrash (Jones, Lopez et al., 2003). It is important to

genital toxoplasmosis on a list

A history ofhydrocephalus,retinochoroiditis,and calcifications inthe central nervoussystem in thenewborn periodshould immediatelyalert a care providerto the possibility oftoxoplasmosis.358 Volume 25 Number 6T. gondii also can invade tissues in the centralnervous system of the developing fetus and can causeareas 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 thecentral nervous system calcifications that are character-istic of this disease. It is believed that these areas of cal-cified tissue are formed from an inadequate amount ofdendritic cells removing necrotic tissue at the affectedsites (Lago et al., 2007). The site of these calcifiedlesions varies to some degree by the gestational age atwhich a developing fetus is exposed to T. gondii. A fe-tus exposed before the 20thweek of gestation oftenwillhave large dense lesions seen in the basal ganglia (Lagoet al., 2007). A fetus exposed between the 20th and 30thweeks of gestation typically will present with smalllesions seen in the lateral ventricles. A fetus exposedafter 30 weeks gestation may have diffuse lesions inthe cerebral parenchyma (Lago et al., 2007).It is important that any infant with suspected or con-

firmed congenital toxoplasmosis receive imaging of thecentral nervous system. A computed tomography (CT)scan and ultrasound are the preferred diagnosticmethods. It is important to use a diagnostic methodthat can adequately pick up areas of calcification inthe infant brain (Lago et al., 2007). CT scanning is thefirst-line diagnostic method used in North America todetect central nervous system abnormalities causedby toxoplasmosis. If concerns exist about the effectsof radiation in the neonatal period, an ultrasound canbe used as an alternative diagnostic method. However,a negative ultrasound in a patient with confirmedcongenital toxoplasmosis may need to be followed bya CT scan for confirmation because ultrasound resultscan vary depending on the examiner and technologyused (Lago et al., 2007). Therefore, in an infant withconfirmed congenital toxoplasmosis or in an infantwho has symptoms, it may be advisable to order a CTscan to limit the amount of diagnostic imaging needed.

PHYSICAL ASSESSMENTOcular ToxoplasmosisToxoplasmosis affects the retina and the underlyingchoroid, causing retinochoroiditis, the most commonmanifestation of ocular toxoplasmosis (Smith &Cunningham, 2002). Retinochoroiditis is described asmacular-pigmented lesions with a central necroticarea primarily found on the retina and can be observedby funduscopic examination. Retinochoroiditis is illus-trated in Figure 2. In more than 50% of cases of ocularcongenital toxoplasmosis, the lesions are found onthe posterior pole of the retina and are unilateral(Bonfioli & Orefice, 2005). Upon examination of theeye, amedical provider will see a gray-white area of ret-inal necrosis with or without exudates with adjacentswelling of the optic disc, vitreitis, vasculitis, andJournal of Pediatric Health Care

hemorrhage (Bonfioli & Orefice, 2005; Smith &Cunningham, 2002). A headlight in the fog isa common description of ocular toxoplasmosis, and itrefers to the retinal inflammation seen through aninfected and opaque vitreous (Bonfioli & Orefice,2005). Active inflammation and infection in the eye typ-ically lasts about 6 weeks, at which time the lesion willbegin to regress, leaving behind a characteristic pig-mented scar on the retina (Smith &Cunningham, 2002).Ocular toxoplasmosis that is allowed to proceed un-

checked without treatment can lead to devastatinglong-term effects. It has been associated with glau-coma, cataracts, vitreous opacification, retinal hemor-rhage or detachment, and optic atrophy. All of theseconditions can lead to permanent blindness (Bonfioli& Orefice, 2005). Ocular lesions can recur in adoles-cence and adulthood, even after treatment in infancy.Follow-up of these patients is extremely important toprevent further damage to the eyes (Phan et al., 2008).

FIGURE 2. Fundoscopic view ofretinochoroiditis. This figure is available incolor online at www.jpedhc.org.Central Nervous System ToxoplasmosisA congenitally exposed infant with central nervous sys-temcalcificationsmayormaynot haveovert neurologicsymptoms. Symptoms that have been documented ininfants with congenital toxoplasmosis include convul-sions, abnormal tearing of the eye, nystagmus, strabis-mus, hearing and visual impairments, and growth anddevelopmental delays (Jones, Lopez et al., 2003).Many of these symptoms overlap with symptoms ofocular toxoplasmosis and could be attributed to eithermanifestation of this parasitic infection (Jedari et al.,2008). Toxoplasmosis can also cause hydrocephalusand microcephaly in the developing fetus (Dimarioet al., 2009).

Sensorineural Hearing Loss and ToxoplasmosisToxoplasmosis also has been associated with sensori-neural hearing loss. A literature review looking at the

www.jpedhc.orgassociation between this parasitic infection and hearingloss found a scarcity of reliable data (Brown et al.,2009). Only five studies met the inclusion criteria forthe literature review, and they reported such differentresults that it is impossible to discern the associationbetween hearing loss and toxoplasmosis (Brownet al., 2005). Although the association and cause arenot fully understood at this time, a nurse practitionershould be aware that the hearing of any childwith a his-tory of toxoplasmosis should be evaluated on a regularbasis and that the child should be referred to an audiol-ogist and ear, nose and throat specialist for follow-up(Brown et al., 2005).

DIAGNOSTIC TESTSThe prevention and treatment of congenital toxoplas-mosis begins with identifying infection in pregnantwomen. Antibody testing that measures the amount ofIgG and IgM is used to confirm exposure to T. gondii.IgG and IgM levels rise within 2 weeks of being ex-posed to the parasite (Jones, Lopez et al., 2003). Ele-vated IgG levels confirm a patient has been exposedto the parasite but do not differentiate between a recentexposure and an exposure that occurred in the past be-cause IgG will persist at a low level throughout the lifeof the patient (Jones, Lopez et al., 2003). IgM antibodylevels can be used to confirm an acute exposure, andthe degree of elevation can be used to discern whenthe exposure occurred (Lopez et al., 2000). AlthoughIgM antibodies are almost always present followingan acute exposure, they can persist in some patientsat high levels for up to 18 months, leading to an inaccu-rate assessment of when the exposure occurred. Thissituation can be problematic because congenital toxo-plasmosis occurs when the mother is infected duringher pregnancy, and the severity of the disease is deter-mined by ascertainingwhen in the pregnancy the infec-tion occurred (Nascimento, Suzuki, & Rossi, 2008). Asignificant increase in specific antibody titers or sero-conversion during pregnancy is usually considered di-agnostic of a recent exposure (Nascimento et al., 2008).Despite serologic evidence demonstrating the likeli-

hood of recent exposure, a T. gondii reference labora-tory must confirm the diagnosis, in part because ofquestions about the sensitivity and specificity of IgGand IgM antibody testing (Tamma & Serwint, 2007).The Sabin FeldmanDye test is performedby a referencelaboratory and is considered the gold-standard diag-nostic test for toxoplasmosis. This test detects a changeinT. gondiispecific antibody titers (IgG) over a 3-weekperiod or detects a single elevated (IgG) antibody titer(Rorman et al., 2006). A four-fold increase in titer levelsover a three-week period or a single titer above 250 IU/ml is considered highly suggestive of infection (Rormanet al., 2006). Polymerase chain reaction testing of amni-otic fluid is the preferred method for providing confir-mation of fetal exposure (Jones, Lopez et al., 2003).November/December 2011 359

enital Toxoplasmosis Studyound that treatment with themedications significantly de-nd symptoms associated withs, including ocular and centralms and sensorineural hearing). This combination of medica-ed by the American Academyatients with sensitivity to sulfa-be used in combination with

ernative (AAP, 2009). Informa-dications and other alternative

TABLE.Medicationsusedto

treattoxoplasmosis

Medication

Mechanismofaction

Dose

Length

oftherapy

Adverseeffects

Sulfadiazine*

Inhibits

folic

acid

synthesis

100mg/kg/daydividedevery12hours

1year

Bonemarrowsuppression,fever,

vasculitis,rash,nausea,vomiting,

nephropathy

Pyrimethamine*

Inhibits

tetrahydrofolic

acid

synthesis

1mg/kg/day

1mg/kg/daythreetim

esperweek

First6months

Second6months

Bonemarrowsuppression,rash,

seizures,

fever,vomiting,diarrhea,

hematuria

Folinicacid

(leucovorin

)*Areducedform

offolic

acid

5-10mgevery

3days

10mgthreetim

esperweek

First6months

Second6months

Rash,erythema,urticaria,wheezing,

thrombocytosis,

hypersensitivity

Trim

ethoprim

sulfamethoxazole

Inhibits

dihydrofolic

acid

synthesis

Consultinfectiousdisease

specialist

Consultinfectiousdisease

specialist

Bonemarrowsuppression,

hypotension,rash,seizures,

fever

Clindamycin

Inhibits

proteinsynthesis

Nostandard

dose;dose

isbasedon

weightandpostnatalage;consult

infectiousdisease

specialist

fordosing

Consultinfectiousdisease

specialist

Pseudomembranouscolitis,

hypotension,cardiacarrhythmia,

rash,bonemarrowsuppression

Azithromycin

Inhibits

proteinsynthesis

Consultinfectiousdisease

specialist

Consultinfectiousdisease

specialist

Palpitations,

chest

pain,QT

prolongation,d

iarrhea,nausea,rash,

ototoxicity,hypersensitivity

*Standard

ofcare.medications that could be used to treat toxoplasmosiscan be found in the Table (Soheilian et al, 2005;Taketomo, Hodding, & Kraus, 2008). A provider alsomay add a corticosteroid to decrease the inflammationcaused by the replication of the parasite and tomanage the associated ocular complications (AAP,2009; Soheilian et al., 2005).Both pyrimethamine and sulfadiazine act by inhibit-

ing folic acid synthesis in T. gondii. By using differentmechanisms of action, they complement one anotherto create a combined effect (Schmidt et al., 2006).Although they have been proven effective, they do notcome without serious adverse effects and should neverbe prescribed without diagnostic confirmation of toxo-plasmosis (Schmidt et al., 2006). As previously stated,spective study calledChicago Based Cong(NCCBTS). This study fthree aforementionedcreased adverse signs acongenital toxoplasmosinervous system symptoloss (McLeod et al., 2006tions also is recommendof Pediatrics (AAP). For pdiazine, clindamycin canpyrimethamine as an alttion regarding these meThis test should be performed at or after 18 weeks ges-tation and only in women with preliminary positiveserologic results indicative of acute exposure(Montoya & Remington, 2008). Polymerase chain reac-tion testing of cerebrospinal fluid also can be used toconfirm the presence of infection in the central nervoussystem after birth (Tamma & Serwint, 2007).

TREATMENTStandard of CareThe goal of initiating treatment is to arrest the replicationof the parasite and prevent further damage to the organsinvolved. It is especially important to stop replication inthe eye to prevent irreversible damage to the retina andoptic nerve that can lead to permanent blindness(Soheilian et al., 2005).Currently, The WorldHealth Organizationand the Centers for Dis-ease Control and Pre-vention recommendpyrimethamine, sulfa-diazine, and leucovorinas the standard ofcare for persons withcongenital toxoplas-mosis (Rorman et al.,2006). These medica-tions were proven to be effective in a randomized pro-

the National Collaborative

Thegoal of initiatingtreatment is toarrest thereplication of theparasite andprevent furtherdamage to theorgans involved.360 Volume 25 Number 6 Journal of Pediatric Health Care

pyrimethamine decreases the synthesis of folic acid bothin T. gondii and in its human host. Thus a major adverseeffect of this treatment regimen is bonemarrowsuppres-sion (Schmidt et al., 2006). Bone marrow suppressionleads to neutropenia, anemia, and thrombocytopenia.This adverse effect may be avoided with the simulta-neous administration of folic acid during treatment(Schmidt et al., 2006; Soheilian et al., 2005).Leucovorin, a folic acid derivative, also can be used tocombat myelosuppression and is given concurrentlywith pyrimethamine and sulfadiazine (Jones, Lopezet al., 2003). Despite these preventative measures,weekly monitoring of cell counts and platelet countsshould be done to assess the level of marrow suppres-sion 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, 3months of therapy may be sufficient to eradicate theparasite andprevent long-termeffects aswell as decreasethe burden of long-term medication usage on theaffected infant and family (Freeman et al., 2008). How-ever,most treatment recommendations suggest that deci-sions concerning whether therapy should be continuedor discontinued be based on patient response to therapyaswell as the severity of symptoms and the age of the pa-tient at the timeofdiagnosis (Schmidt et al., 2006). Resultsfrom the NCCBTS study and the AAP recommend treat-ment 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 thereis still debate regarding dosages and length of therapy,and thus a specialist in infectious disease andtoxoplasmosis should be consulted prior to treatmentinitiation or treatment discontinuation (AAP, 2009).

Treatment for Expectant MothersTreatment of a woman during pregnancy also has beenstudied to prevent congenital toxoplasmosis. Duringthe first trimester of pregnancy, pyrimethamine is con-traindicated because of the teratogenic effects of thismedication. Sulfadiazine may be used alone duringthe first trimester and pyrimethamine may be addedto the regimen after this crucial period of fetal develop-ment if the benefit of this drug outweighs the risk to thefetus (Freeman et al., 2008). Although not yet approvedby the Food and Drug Administration in the UnitedStates, another medication called spiramycin is usedto prevent transplacental infection in many other coun-tries. Spiramycin is available in the United States underspecial circumstances as an investigational medication(Rorman et al., 2006).Overall, the research pertaining to anti-toxoplasmic

treatment is lacking. The majority of studies are retro-spective, and few randomized control trials exist thatlook at medication efficacy. More research must bedone in this area to develop the best treatment forwww.jpedhc.orgpregnant women and neonates congenitally exposedto T. gondii.

NEONATAL SCREENINGScreening for toxoplasmosis is a controversial topic. Inpopulations with a low prevalence, screening of preg-nant mothers is not believed to be cost-effective, noris treatment during pregnancy guaranteed to preventcongenital toxoplasmosis (Dimario et al., 2009).Screening in the neonatal periodmaybe amore feasibleoption for primary care providers (Jara, Hsu, Eaton, &Demaria, 2001). In 1986, Massachusetts added toxo-plasmosis to its newborn screening and createdfollow-up recommendations for infants with positiveserologic findings (Jara et al., 2001). Currently in theUnited States, Massachusetts and New Hampshire arethe only two states that routinely screen for toxoplas-mosis at birth. IgM and IgG antibody testing is used toscreen all infants in these two states at the same timethat all other newborn screening is conducted (Jaraet al., 2001). It is important to note that positive sero-logic results demonstrate that the mother has beenexposed and do not definitively indicate congenitaltoxoplasmosis in the infant (Jara et al., 2001). Theresults simply allow the primary care provider to beaware of the possibility and provide further follow-upas indicated.Preliminary data from these two states suggest that

the prevalence of congenital toxoplasmosis is 1 in12,000 live births and that providing treatment tothese infants early in life significantly decreases theneurologic and ophthalmologic effects of this disease(Jara et al., 2001). Between 1986 and 1992, 52 infantsin Massachusetts and New Hampshire were identifiedas having been congenitally infected. Fifty of these in-fants were identified through neonatal screening alone,and after 1 year of treatment, only one infant demon-strated a neurologic deficit and four infants demon-strated lesions in the eye (Lopez et al., 2000). Thusthese preliminary data demonstrate that early screeningand treatment can significantly decrease the long-termsequelae of congenital toxoplasmosis. Neonatalscreening has limitations, however, and should neverbe used as diagnostic confirmation of congenital toxo-plasmosis because the sensitivity and specificity of suchtesting, especially using filtered blood samples, is lowand could provide false results (Dimario et al., 2009).

ROLE OF THE NURSE PRACTITIONERImplications for Clinical PracticePNPs play an important role in recognizing and treatingcongenital toxoplasmosis. Because screening for toxo-plasmosis does not always occur during the prenatalperiod, many prenatal infections go unnoticed and un-documented. A mother may be unaware that she hasbeen exposed to the parasite and unaware of the risksthat T. gondii can pose to her infant. The first step forNovember/December 2011 361

for example, also can limit theoman may have with thesePinard et al., 2003). The skinstables should be washed andse oocysts may be attached toand could be ingested. Again,strongly emphasized after han-luding fruits, vegetables, andal., 2000).T. gondii cysts can re-different types of mammals ors, it is estimated that 8% of beefkmeat contains T. gondii tissueall PNPs in primary care is to be aware of this infectionand to ask each new mother about her possible expo-sure to the organism. Important screening questionspresented in Box 2 should be asked at newborn visitsand any prenatal visits. These questions can providean idea of the level of risk andwhether congenital toxo-plasmosis is a possibility, especially if any abnormalitiesare noted in the newborn.An infant that has been congenitally exposed to

T. gondii will require medical care, monitoring, andfollow-up throughout infancy, childhood, and adoles-cence. A PNP can provide a medical home and cancoordinate primary care with specialty care includingophthalmology, neurology, audiology, and infectiousdisease specialists, depending on the clinical needs ofthe patient. Although treatment during infancy can

BOX 2. Important screening questions forToxoplasma gondii seronegative expectantmothers to assess the risk of T. gondiiexposure

Questions

d Do you own a cat?d If you own a cat, does your cat go outdoors or hunt andeat raw meat?

d Do you garden?d Do you work or participate in any activity where you aredirectly exposed to sand, dirt, or soil?

d Do you eat meat? If yes, how is it prepared?d Do you eat raw fruit and vegetables? If yes, how are theyprepared?

d Have you traveled to any foreign countries? If yes,whereand what did you eat, and did you drink the water?

Based on the answers to these questions, a practitionercanprovide thenecessary education toprevent exposure.decease the long-term effects of congenital toxoplas-mosis, children and adolescents whowere treated in in-fancy are still at risk for ocular complications later in life.Because of this risk, it is important to ensure thatpatients receive routine ophthalmologic monitoring toidentify ocular complications before they lead topermanent damage of the eye (Phan et al., 2008).

Patient EducationIn the United States it is estimated that 85% of pregnantwomen have never been exposed to T. gondii and thusare at risk for contracting the parasite during pregnancy(Jones, Ogunmodede et al., 2003). Prevention of con-genital toxoplasmosis begins with preventing primaryinfection. Despite the fact that T. gondii can be avoidedby implementing relatively simple strategies in dailylife, the majority of pregnant women are unaware ofhow to prevent exposure (Jones, Ogunmodede et al.,2003). A survey of 400 pregnant women in the UnitedStates demonstrated that only half were aware of

362 Volume 25 Number 6cysts (Kravetz & Federman, 2005). All pregnant womenshould be taught to never ingest raw meat and to cookall meat to an internal temperature of at least 152F todestroy the tissue cysts (Kravetz & Federman, 2005).Because cats are theprimaryhost forT. gondii, it is im-

portant that pregnant women be aware of the risks theymay pose. Contact with cat litter should be avoided ifpossible, and if contactis unavoidable, glovesshould be worn whilechanging the litter boxand hands should bewashed thoroughly af-terward (Lopez et al.,2000; Pinard et al.,2003). Frequent litterchanges should bedone because it takesseveral days foroocysts to becomeinfectious, and the box should be thorou-ghly cleaned with disinfecting agents (Lopez et al.,2000; Pinard et al., 2003). Preventing a cat fromhunting outdoors or eating raw meat also can preventthe feline from being infected with T. gondii.Practitioners should encourage pregnant women tokeep indoor-only cats and to feed them only cannedor dry food that has been bought in a store (Lopezet al., 2000).Providing education to expectant mothers is an im-

portant part of the provision of primary care for PNPs.A practitioner should providematerials and information

Because cats arethe primary host forT. gondii, it isimportant thatpregnant womenbe aware of therisks they maypose.(Dimario et al., 2009;gloves while gardening,contact a pregnant wenvironmental hazards (of all raw fruit and vegethen peeled away becauthese parts of the foodhandwashing should bedling any raw food incmeat products (Lopez etside in the meat of manybirds. In the United Stateand 20%of lamb andportoxoplasmosis. Most of these women knew toxoplas-mosis was associated with cat litter but were unsureas to why and did not know about exposure in theenvironment 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 inthese substrates (Lopez et al., 2000). Limiting contactwith dirt, sand, or soil can help prevent the ingestionof oocysts from the environment, and if contact occurs,an expectant mother should be taught to thoroughlywash her hands to avoid ingesting the parasite

Lopez et al., 2000). WearingJournal of Pediatric Health Care

givFIGURE 3. An example of a handout that could bein color online at www.jpedhc.org.in a variety of languages and use common language in-stead of medical jargon to teach important points to pa-tients. Handouts that are culturally sensitive andappropriate for mothers with low literacy skills or whocannot read should be used (Montoya & Remington,2008). Using pictures and color demonstrations ofhand washing, cooking, and wearing gloves may behelpful when teaching about toxoplasmosis if transla-tion into another language is difficult (Montoya &Remington, 2008). In addition, creating handouts thata patient can simply hang in the home as a quick re-minder may be useful. Figure 3 is an example of a hand-out for expectantmothers. Although research that looksat the role of prenatal education in preventing congen-ital toxoplasmosis is limited, current recommendationssuggest that all pregnant women be given informationthrough written materials and discussions with medicalproviders (Dimario et al., 2009). PNPs play an importantrole in providing this information to their patients and toexpectant mothers.

www.jpedhc.orgen to expectantmothers. This figure is availableCONCLUSIONPNPs play an active role in the primary care of infants. APNP may be the first medical provider who sees a new-born after he or she is released from the hospital andcan provide primary care throughout infancy and child-hood. It is important that PNPs be able to recognize anddiagnose congenital toxoplasmosis as well as provideand coordinate treatment and long-term follow-upcare for these patients.

The author wishes to thank Dr. Rita Marie John,CPNP, DNP, EdD, Columbia University School ofNursing, for her guidance and review of this article.

REFERENCESAmerican 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 Committeeon Infectious Diseases (28th ed.). Elk Grove Village, IL: Author.

Bonfioli, A. A., & Orefice, F. (2005). Toxoplasmosis. Seminars inOphthalmology, 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 toxoplas-mosis exposure and sensorineural hearing loss. InternationalJournal of Pediatric Otorhinolaryngology, 73(5), 707-711.

Dimario, S., Basevi, V., Gagliotti, C., Spettoli, D., Gori, G., DAmico, R.,. Magrini, N. (2009). Prenatal education for congenitaltoxoplasmosis. Cochrane Database of Systematic Reviews, 2,1-18.

Dubey, J. P. (2004). Toxoplasmosis: A waterborne zoonosis. Veteri-nary Parasitology, 126, 57-72.

Freeman, K., Tan, H. K., Prusa, A., Peterson, E., Buffolano, W.,Malm, G., . Gilbert, R. (2008). Predictors of retinochoroiditisin children with congenital toxoplasmosis: European prospec-tive cohort study. Pediatrics, 121(5), 1215-1222.

Gerber, S., & Hohlfeld, P. (2003). Screening for infectious diseases.Childs Nervous System, 19, 492-432.

Holland, G. N. (2003). Ocular toxoplasmosis: A global reassessment.Part 1: Epidemiology and course of disease. American Journalof Ophthalmology, 136(6), 973-988.

Based, Congenital Toxoplasmosis Study. Clinical InfectiousDiseases, 42(10), 1383-1394.

Montoya, J. G., & Remington, J. S. (2008). Management ofToxoplasma gondii infection during pregnancy. Clinical Infec-tious Diseases, 47(4), 554-566.

Nascimento, F. S., Suzuki, L. A., & Rossi, C. L. (2008). Assessment ofthe value of detecting specific IgA antibodies for the diagnosis ofa recently acquired primary Toxoplasma infection. PrenatalDiagnosis, 28(8), 749-752.

Phan, L., Kasza, K., Jalbrzikowski, J., Noble, A. G., Latkany, P.,Kuo, A., . McLeod, R. (2008). Longitudinal study of neweye lesions in treated congenital toxoplasmosis. AmericanJournal of Ophthalmology, 115(3), 553-559.

Pinard, J. A., Leslie, N. S., & Irvine, P. J. (2003). Maternal serologicscreening for toxoplasmosis. Journal of Midwifery andWomens Health, 48(5), 308-316.

Pradhan, S., Yadav, R., & Mishra, V. N. (2007). Toxoplasma menin-goencephalitis in HIV-seronegative patients: Clinical patterns,imaging features and treatment outcome. Transactions of theJara, M., Hsu, H. W., Eaton, R., & Demaria, A. (2001). Epidemiologyof congenital toxoplasmosis identified by population-basednewborn screening in Massachusetts. The Pediatric InfectiousDisease Journal, 20(12), 1132-1135.

Jedari, A. S., Maliky, Z., & Daneshjou, K. (2008). A 10 month old withnystagmus and strabismus. Pakistan Journal of BiologicalSciences, 11(5), 817-818.

Jones, J. L., Lopez, A., & Wilson, M. (2003). Congenital toxoplasmo-sis. 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 AmericanJournal 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 relatedknowledge and practices among pregnant women in the UnitedStates. Infectious Diseases in Obstetrics and Gynecology,11(3), 139-145.

Kravetz, J. D., & Federman, D. G. (2005). Toxoplasmosis in preg-nancy. 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 ultrasonographyand computed tomography in detecting intracranial calcifica-tions 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 Recommenda-tions 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 Toxo-plasmosis, 1981-2004: The National Collaborative Chicago-364 Volume 25 Number 6Royal 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). Congen-

ital toxoplasmosis-prenatal aspects of toxoplasma gondiiinfection. 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 congenitaltoxoplasmosis in Brazil. The Brazilian Journal of InfectiousDiseases, 7(5), 325-331.

Schmidt, D. R., Hogh, B., Anderson, O., Hansen, S. H., Dalhoff, K., &Peterson, E. (2006). Treatment of infants with congenital toxo-plasmosis: Tolerability and plasma concentrations of sulfadia-zine and pyrimethamine. European Journal of Pediatrics,165(1), 19-25.

Smith, J. R., & Cunningham, E. T. (2002). Atypical presentations ofocular 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 randomizedtrial of trimethoprim/sulfamethoxazole versus pyrimethamine andsulfadiazine in the treatment of ocular toxoplasmosis. Ophthal-mology, 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). Pediatricdosage 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 prognosisin 327 children with congenital toxoplasmosis. Pediatrics,113(6), 1567-1572.Journal of Pediatric Health Care

Toxoplasmosis: Diagnosis, Treatment, and Prevention in Congenitally Exposed InfantsEpidemiologyPathophysiologyVertical transmissionRisk factorsClinical presentationPhysical assessmentOcular ToxoplasmosisCentral Nervous System ToxoplasmosisSensorineural Hearing Loss and Toxoplasmosis

Diagnostic testsTreatmentStandard of CareTreatment for Expectant Mothers

Neonatal screeningRole of the nurse practitionerImplications for Clinical PracticePatient Education

ConclusionReferences