CLINICAL PRACTICE INVITED ARTICLE

Ellie J. C. Goldstein, Section Editor

Management of Toxoplasma gondii Infection

during Pregnancy
Jose G. Montoya and Jack S. Remington
Palo Alto Medical Foundation Toxoplasma Serology Laboratory, Palo Alto, and Department of Medicine and Division of Infectious Diseases and Geographic Medicine,
Stanford University School of Medicine, Stanford, California

Acute infection with Toxoplasma gondii during pregnancy and its potentially tragic outcome for the fetus and newborn
continue to occur in the United States, as well as worldwide, despite the fact that it can be prevented. The infection can be
acquired through ingestion of infected, undercooked meat or contaminated food or water. Transmission to the fetus occurs
almost solely in women who acquire their primary infection during gestation and can result in visual and hearing loss,
mental and psychomotor retardation, seizures, hematological abnormalities, hepatosplenomegaly, or death. Systematic ed-
ucation and serological screening of pregnant women are the most reliable and currently available strategies for the prevention,
diagnosis, and early treatment of the infection in the offspring; this is largely because toxoplasmosis in pregnant women
most often goes unrecognized. Treatment of the infection in the fetus and infant during the first year of life has been
demonstrated to significantly improve the clinical outcome.

Toxoplasma gondii infection acquired by pregnant women dur- diagnosis and management of toxoplasmosis during pregnancy
ing gestation and its transmission to the fetus continue to be in the United States. A more comprehensive review of the sub-
the cause of tragic yet preventable disease in the offspring [1]. ject can be found elsewhere [1].
In addition to the unfortunate outcome for infants and children
are the emotional and economic burdens faced by the parents CLINICAL MANIFESTATIONS DURING
and society. It has been estimated that 5005000 infants each PREGNANCY
year are born with congenital toxoplasmosis in the United
Transmission to the fetus occurs predominantly in women who
States [2]. Although the majority of infants appear to be healthy
acquire their primary infection during gestation. In rare cases,
at birth, significant long-term sequelae may become obvious
congenital transmission has occurred in chronically infected
only months or years later.
women whose infection was reactivated because of their im-
T. gondii infection is acquired primarily through ingestion
munocompromised state (e.g., from AIDS or treatment with
of cysts in infected, undercooked meat or oocysts that may
corticosteroids for their underlying disease).
contaminate soil, water, and food. Meat (primarily pork and
Most pregnant women with acute acquired infection do not
lamb) is an important source of the infection in humans in
experience obvious symptoms or signs [1, 9]. A minority may
the United States [3]. However, the frequency at which the
experience malaise, low-grade fever, and lymphadenopathy.
source is meat versus ingestion of oocysts among different pop-
Rarely, pregnant women will present with visual changes due
ulations and geographical areas in the United States is un-
to toxoplasmic chorioretinitis [10] as a result of recently ac-
known. Recent studies have identified water as a potential
quired infection or reactivation of a chronic infection. A recent
source of the infection in both humans and animals [48].
study revealed that 52% of mothers who gave birth to con-
The purpose of this review is to provide an update on the
genitally infected offspring could not recall experiencing an
infection-related illness during pregnancy or an identifiable ep-
Received 15 January 2008; accepted 16 March 2008; electronically published 11 July 2008.
Reprints or correspondence: Dr. Jose G. Montoya, Research Institute, Palo Alto Medical
idemiological risk factor [9]. In severely immunocompromised,
Foundation, Ames Bldg., 795 El Camino Real, Palo Alto, CA 94301 ([email protected]). chronically infected pregnant women (e.g., patients with AIDS
Clinical Infectious Diseases 2008; 47:55466 and those receiving high-dose immunosuppressive therapy, in-
 2008 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2008/4704-0019$15.00
cluding organ transplant recipients, patients with malignancies,
DOI: 10.1086/590149 and patients with connective tissue disorders), reactivation of

554 CID 2008:47 (15 August) CLINICAL PRACTICE

latent T. gondii infection resulted in congenital transmission of of recently acquired infection. Although we support the use of
the parasite to the fetus [1113]. systematic serological screening during pregnancy, we acknowl-
edge that factors such as cost, demographic characteristics,
SPECIAL CONSIDERATIONS IN THE FETUS availability of appropriate tests, and the relatively low incidence
AND NEWBORN RELATED TO MATERNAL of acute infection must be taken into consideration. An ad-
INFECTION ditional consideration is the recent controversy about the ef-
The frequency of vertical transmission increases with the ges- fectiveness of treatment during gestation in an attempt to pre-
tational age (table 1) [1, 14]. In contrast, severe clinical signs vent transmission to the fetus.
in the infected infant are more commonly observed in offspring Serological tests. The detection (and quantification) of T.
of women whose infection was acquired early in gestation (ta- gondii antibodies in serum is used to establish whether a preg-
ble 1). nant woman has been infected and, if so, to determine whether
Occasionally, the diagnosis of the infection in a pregnant the infection was acquired recently or in the distant past. If
woman is first considered when ultrasonographic findings re- serological test results suggest a recently acquired infection, an
veal the presence of fetal abnormalities [1]. In other cases, it effort is made to determine whether the infection was likely
is first considered in a mother whose newborn has clinical acquired during gestation or shortly before conception. If so,
manifestations of the infection. the fetus is at risk.
In the United States, physicians most often submit only a
DIAGNOSIS DURING PREGNANCY single serum sample for serological testing, and from the results
for that specimen, they expect a diagnosis. Thus, seroconversion
Serological tests and PCR are used in an attempt to diagnose
toxoplasmosis in pregnant women (table 2) [1]. Transmission is rarely demonstrable in the United States. Only approximately
of the parasite to the fetus frequently occurs in pregnant women one-third of the samples submitted to our serology laboratory
who have no history of illness during gestation or exposure to are obtained from women in their first trimester [1]. Serological
undercooked meat or to cats [9]. Therefore, the decision to test results of serum samples obtained later in gestation are
perform T. gondii serological tests during pregnancy should not frequently difficult to interpret. The earlier the serum sample
be based solely on clinical (e.g., presence or absence of symp- is obtained, the more likely the results will prove clinically
toms) or epidemiological (i.e., history of exposure to T. gondii) helpful. Testing of a serum sample drawn after the second tri-
grounds [1, 9]. mester most often will not be able to exclude that an infection
Systematic serological screening for T. gondii IgG and IgM was acquired earlier in the pregnancy.
antibodies in all pregnant women as early in gestation as feasible For serological diagnosis, IgG, IgM, IgA, and IgE antibodies;
(ideally during the first trimester) and in seronegative women IgG avidity; and the differential agglutination (AC/HS) tests
each month or trimester thereafter would be optimal. Such have been employed successfully in an attempt to distinguish
screening allows for detection of seroconversion and early ini- the acute versus the chronic stage of the infection [15]. Except
tiation of treatment. Although screening is rarely performed in for measurement of IgG and IgM antibodies, most of these
the United States, such screening is mandated by law in some tests are performed only in reference laboratories (e.g., in the
countries (e.g., France and Austria), to facilitate early detection United States, at the Palo Alto Medical Foundation Toxoplasma

Table 1. Risk of Toxoplasma gondii congenital infection (transmission) and development of

clinical signs in offspring before age 3 years, according to gestational age at maternal
seroconversion.

Gestational age Risk of development

at maternal Development of clinical of clinical signs when
seroconversion, Risk of congenital signs in the infected infection status is
weeks infection (95% CI), % offspring (95% CI), % unknown,a %
13 6 (39) 61 (3485) 4
26 40 (3347) 25 (1833) 10
36 72 (6081) 9 (417) 7

NOTE. This analysis was performed with 603 women whose T. gondii infection was documented to have
occurred during gestation. Anti-Toxoplasma treatment was administered to 504 (84%) of the women. Data are
from [14].
a
Risk of development of clinical signs of infection in a child whose mother was known to have been infected
during gestation but in whom congenital infection has not been established yet (values are obtained by multiplying
the risk of congenital infection by the risk of signs among congenitally infected children).

CLINICAL PRACTICE CID 2008:47 (15 August) 555

Table 2. Laboratory tests available for diagnosis of toxoplasmosis during pregnancy and the distinguishing features between serological testing at nonreference laboratories
and at Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL).

Diagnostic tests Use Available tests Storage of serum samples Assistance to clinicians

Serological tests
At nonreference or commercial laboratory Useful for initial screening because only IgG: positive or negative results are usu- Samples are usually discarded Usually not available
10% of pregnant women in the US are ally reliable; IgM: negative results are after testing and are not
seropositive most often reliable, and positive or available for future parallel
equivocal results require confirmatory testing
testing at reference laboratory
a
At reference laboratory (PAMF-TSL ) Particularly useful for pregnant women with IgG (dye test), IgM, IgA, IgE, AC/HS, avid- Samples are stored for 1 Provided by physician consultants
positive or equivocal IgM test results ity, agglutination year for potential future par-
allel testing
Amniotic fluid PCR Should be performed at 18 weeks of gesta-
tion or as soon as feasible thereafter for
pregnant women with suspected or proven
toxoplasmosis during pregnancy; 35-multi-
copy B1 gene is commonly used as the
target
Ultrasound Should be performed (ideally every month)
for pregnant women with suspected or
proven T. gondii infection acquired during
pregnancy
a
http://www.pamf.org/serology/; telephone number (650) 853-4828; e-mail, [email protected].
Serology Laboratory [PAMF-TSL]; Palo Alto, CA; http:// pretation of results and limits the ability to provide appropriate
www.pamf.org/serology/; telephone number (650) 853-4828; recommendations.
e-mail, [email protected]). Currently, the IgG avidity test is It needs to be emphasized that a positive IgM antibody test
not commercially available in the United States. Ongoing stud- result at any time before or during gestation does not necessarily
ies at PAMF-TSL are in progress with the VIDAS IgG avidity mean a recently acquired infection [1618]. IgM antibodies
kit (bioMerieux), which is widely used in western Europe. An may persist for 1 year following acute infection, and most
avidity test is also available at FOCUS Laboratories (Cypress, positive IgM antibody test results are obtained in pregnant
CA). women who acquired their infection in the more distant past
Serological testing for both IgG and IgM antibodies at clin- and beyond the period of fetal risk. These patients are chron-
ical, nonreference laboratories should be performed initially. In ically infected. Recently, we examined 100 consecutive serum
the vast majority of cases, testing early in gestation can establish samples submitted to PAMF-TSL because of a positive IgM
either that infection has not occurred, by the absence of both antibody test result at an outside clinical laboratory. Confir-
IgG and IgM antibodies, or that infection was acquired in the matory testing at PAMF-TSL revealed that 62% of these serum
distant past, by positive IgG and negative IgM antibody test samples were negative for IgM antibody. This percentage is
results (table 3). Additional assistance with confirmatory testing essentially the same as that we reported 7 years ago [19]. Ad-
in reference laboratories is required primarily for patients with ditional testing confirmed that infection in such cases was ac-
positive or equivocal IgM antibody test results. A reference quired in the more distant past rather than recently. The greatest
laboratory such as PAMF-TSL often can determine whether a value of a positive IgM antibody test result is that it raises the
patient with a positive IgM antibody test result acquired the question of a recently acquired infection, thereby necessitating
infection recently or in the distant past. confirmatory testing in a reference laboratory.
Physicians and laboratory personnel should realize the sig- Figure 1 shows interpretation of results of serological tests
nificant and often unfortunate delays that may occur between performed at clinical laboratories. Serological testing for both
the date that the serological tests are ordered and the date that IgG and IgM antibodies at clinical (nonreference) laboratories
the results are actually reported back to the health care provider should be performed initially. Negative results of Toxoplasma
and the patient. This is particularly the case when results ob- IgG and IgM antibody tests, as well as positive results of IgG
tained at nonreference laboratories require confirmatory testing tests, tend to be accurate. Initial screening and testing for tox-
at a reference laboratory. oplasmosis can be accomplished by these laboratories (table 3).
Appropriate interpretation of serological test results can best Figure 2 shows the procedure for confirmatory testing of
be achieved when adequate clinical information (i.e., gestational positive IgM test results at a reference laboratory. A battery of
age, reason for testing, and presence of abnormal clinical or serological tests is usually required in an attempt to establish
laboratory findings in the mother or the fetus) is made available whether a positive or equivocal IgM test result is clinically
to experienced consultants. Too frequently, serological tests are relevant (i.e., whether it is indicative of an infection acquired
requested, but information about the patient is not provided. during gestation) [17]. It is noteworthy that only 40% of
Lack of clinical information often results in suboptimal inter- positive IgM test results obtained at nonreference laboratories

Table 3. Interpretation of results of serological tests for toxoplasmosis performed at clinical (nonreference) laboratories.

IgG test result IgM test result Clinical relevance

Negative Negative Interpreted to indicate that the woman has not been infected with Toxoplasma gondii.
Serial testing during pregnancy is advised. If such women acquire primary infection
during gestation, they are at risk of transmitting the infection to their fetus.
Positive Negative During the first or second trimester, most often reflects an infection acquired before the
present pregnancya
Negative Positive or equivocal IgM antibodies are detected early in the acute infection. Because they may persist for
prolonged periods, IgM antibodies may be detected in pregnant women who were
infected in the distant past and before gestation. Therefore, a positive (or equivocal)
IgM test result should be followed by confirmatory testing at a Toxoplasma reference
laboratoryb [17]
Positive Positive or equivocal Same as above
a
In the third trimester, this result is more difficult to interpret. Although it is most consistent with an infection acquired before pregnancy, in some patients,
this result may reflect an infection that was acquired early in gestation and that was accompanied by an increase in the IgM titer and a decrease to nondetectable
levels within a relatively brief period of time.
b
For example, the Palo Alto Medical Foundation Toxoplasma Serology Laboratory, telephone number (650) 853-4828; e-mail, [email protected].

CLINICAL PRACTICE CID 2008:47 (15 August) 557

Figure 1. Guidelines for serological testing and management of toxoplasmosis during pregnancy on the basis of initial results obtained from
Toxoplasma gondii IgG and IgM antibody tests performed at clinical (nonreference) laboratories. 1Initial serological screening with IgG and IgM tests
usually can be reliably performed at nonreference laboratories. Certain laboratories or clinicians may choose to send serum samples at this initial
stage directly to a reference laboratory; interpretation of results obtained in a reference laboratory usually will be the same as that shown here for
nonreference laboratories. 2The interval for serological screening varies by the center and country where systematic serological screening is performed
(e.g., every month in France). Systematic serological screening to detect early infection acquired during gestation is not performed in the United States.
3
Consider consultation with a physician expert in management of toxoplasmosis during pregnancy (e.g., at Palo Alto Medical Foundation Toxoplasma
Serology Laboratory [PAMF-TSL], telephone number (650) 853-4828, or US [Chicago, IL] National Collaborative Treatment Trial Study, telephone number
(773) 834-4152). 4Consider sending samples to a reference laboratory such as PAMF-TSL [17]. 5Treatment with spiramycin or with pyrimethamine,
sulfadiazine, and folinic acid (see text and table 6). 6Amniotic fluid PCR should be performed at 18 weeks of gestation (not before) or later. In patients
at 118 weeks of gestation, the risk of the procedure should be carefully weighed against the potential benefit of diagnosing fetal infection (see text
and tables 2 and 5). CT, congenital toxoplasmosis.

in the United States were found for patients who had acquired regard to decisions about prenatal drug intervention(s) and
their primary (acute) infection in the recent past [19]. additional diagnostic tests, such as PCR and ultrasound. In
Confirmatory testing of a positive IgM test result by the use addition, correct interpretation of the TSP results and their
of additional tests in various combinations has been validated communication to the patients physician by an expert were
by reference laboratories in Europe and the United States (tables reported to decrease the rate of unnecessary abortions by 50%
2 and 4) [15, 20, 21]. An example is the battery of tests (Tox- among women in the United States for whom positive IgM test
oplasma serological profile [TSP]) used at PAMF-TSL. The TSP results had been reported by outside laboratories [19].
comprises the dye test (which measures primarily IgG anti- A Toxoplasma IgG avidity test has also been used at PAMF-
bodies); IgM, IgA, and IgE ELISAs; and the AC/HS test [1]. TSL since July 2000. It is used only in conjunction with the
The methods used for demonstration of IgM, IgA, and IgE AC/HS test and, when indicated, with other tests in the TSP
antibodies at the PAMF-TSL were developed by that laboratory [22, 23]. High-avidity IgG antibodies develop at least 1216
and are not available elsewhere. In addition to the reporting weeks (depending on the test method used) after infection. The
of serological test results, consultants at PAMF-TSL offer med- presence of high-avidity antibodies in the TSP indicates that
ical interpretation of results and are available to assist clinicians infection was acquired 116 weeks earlier [22, 24, 25]. Thus, in
in management of their patients conditions. a pregnant woman in the first months of gestation, regardless
The TSP has been used successfully at PAMF-TSL in attempts of the IgM antibody test result, a high-avidity IgG test result
to determine whether a pregnant woman acquired her infection indicates that the fetus is essentially not at risk for congenital
during or before gestation. This distinction is important with toxoplasmosis. A high-avidity IgG test result is especially useful

558 CID 2008:47 (15 August) CLINICAL PRACTICE

Figure 2. Serological testing and management of toxoplasmosis during pregnancy on the basis of results obtained at the Palo Alto Medical Foundation
Toxoplasma Serology Laboratory (PAMF-TSL), telephone number (650) 853-4828. 1A serum sample with positive results of IgG and IgM antibody tests
is the most common reason for requesting confirmatory testing at PAMF-TSL. 2PAMF-TSL or US (Chicago, IL) National Collaborative Treatment Trial
Study, telephone number (773) 834-4152. 3Treatment with spiramycin or with pyrimethamine, sulfadiazine, and folinic acid (see text and table 6). AC/
HS, differential agglutination test; STRs, serological test results at PAMF-TSL; TSP, Toxoplasma serological panel.

when only a single sample of serum has been obtained in which treatment with spiramycin for the mother unnecessary, to re-
T. gondii IgM antibodies are present and for which the AC/HS move the pregnant womans anxiety associated with further
test (or the TSP) reveals an acute or equivocal pattern. For testing, and to decrease unnecessary abortions. Final interpre-
pregnant women beyond 16 weeks of gestation, a high-avidity tation of results of serological tests performed at PAMF-TSL
test result may be helpful in establishing that the infection was yields 3 possibilities: (1) results are consistent with a recently
acquired at least 1216 weeks earlier in gestation; in this sce- acquired infection, and thus the possibility that the patient
nario, the transmission rate would be lower [14], the potential acquired her infection during gestation or shortly before con-
for fetal damage would be greater (table 1) [14], and the neg- ception cannot be excluded; (2) results are consistent with an
ative predictive value of the amniotic fluid PCR would be infection acquired in the distant past and before pregnancy; or
greater (table 5) [26] than if the infection was acquired later (3) results are equivocal, which usually requires a follow-up
in gestation. Of special note is that low-avidity or equivocal serum sample for parallel testing (figure 2 and table 4).
test results can persist for many months or a year or more after PCR. Amplification of T. gondii DNA in amniotic fluid at
the primary infection and, for this reason, must not be used 18 weeks of gestation (the optimal time) or later has been used
alone to determine whether the infection was recently acquired successfully for prenatal diagnosis of congenital toxoplasmosis
[22, 27]. In fact, in serum samples with low- or borderline- [26, 29, 30]. Its sensitivity and specificity for amniotic fluid
avidity antibodies and negative IgM antibody test results or a obtained before 18 weeks of gestation have not been studied;
TSP reflecting an infection acquired in the distant past, the IgG in addition, the procedure done early in gestation is associated
avidity test is not useful and, if used alone, can potentially be with a higher risk to the fetus and likely is less useful. A de-
misleading [28]. finitive study of the routine use of PCR of amniotic fluid ob-
Confirmatory testing with the TSP and the avidity method tained at 18 weeks of gestation or later was reported in France
during the first 16 weeks of gestation has the potential to de- to have an overall sensitivity of 64% for the diagnosis of con-
crease the need for follow-up serum samples and thereby reduce genital infection in the fetus, a negative predictive value of 88%,
costs, to make the need for PCR of amniotic fluid and for and a specificity and positive predictive value of 100% (i.e., a

CLINICAL PRACTICE CID 2008:47 (15 August) 559

Table 4. Examples of final interpretation of results of confirmatory tests performed at Palo Alto Medical Foundation Toxoplasma
Serology Laboratory (PAMF-TSL) on serum samples that had positive results of IgM antibody tests at clinical laboratories.

Clinical
PAMF-TSL results for test
(nonreference)
Patient laboratory IgG
a
(weeks of results of IgG/ (dye test), AC/HS
gestation) IgM tests IU/mL IgM IgA IgE pattern Avidity Interpretation
A (11) +/+ 8000 + + + Acute Low Consistent with recently acquired infection
B (9) +/+ 256 + Equivocal High Consistent with infection acquired in the distant past
(i.e., 6 months ago)
C (12) +/+ 4096 Nonacute Low Consistent with infection acquired in the distant past
D (12) +/equivocal 1024 + + Equivocal Low Cannot exclude recently acquired infection; test of
earlier or subsequent sample is required for fur-
ther clarification
a
Differential agglutination.

positive result signifies infection of the fetus) (table 5) [26]. highest risk of severe outcome in the fetus. In clinical practice,
Gestational age had a significant influence on the sensitivity amniocentesis has essentially replaced fetal blood sampling for
and negative predictive values [26]. Sensitivity was statistically diagnosis of congenital toxoplasmosis, because of its inherently
significantly higher when maternal infection occurred at 17 lower risk and higher sensitivity [1, 30].
21 weeks of gestation, compared with when infection occurred PCR techniques for detection of T. gondii DNA in amniotic
before 17 weeks or after 21 weeks of gestation (P ! .02) [26]. fluid or other samples are not standardized, and there is no
However, the negative predictive value of PCR of amniotic fluid consensus on the best protocol to use [26, 29, 3134]. The
from women who acquired the infection early in gestation (e.g., specimen should be sent to a laboratory experienced in per-
before week 7 of gestation) was 100% because of the very forming this assay on amniotic fluid and that has proper val-
low transmission rate during that time in gestation [26]. Ro- idation and quality-control data and experience in interpre-
mand et al. [31] also demonstrated that the parasite load in tation of its results.
amniotic fluid is an independent risk factor for severity of fetal Amniotic fluid examination by PCR should be considered
infection, in addition to the gestational age. Maternal infections for pregnant women (without a contraindication for the pro-
acquired before 20 weeks of gestation with a parasite load 1100 cedure) who (1) have serological test results diagnostic or highly
parasites per mL of amniotic fluid was associated with the suggestive of an infection acquired during gestation or shortly
before conception; (2) have evidence of fetal damage by ultra-
Table 5. Rates of congenital transmission in 270 women and sonographic examination (e.g., ventriculomegaly or hepatic or
the sensitivity and negative predictive value (NPV) of amniotic brain calcifications); or (3) are significantly immunosuppressed
fluid PCR for prenatal diagnosis of congenital toxoplasmosis, ac- and thus at risk of reactivation of their latent infection (with
cording to gestational age at which maternal infection was
the exception of women with AIDS). Amniocentesis may be
acquired.
less advisable for patients coinfected with T. gondii and HIV,
Gestational age No. of infectedb because of the risk of infecting the fetus with HIV during the
Amniotic fluid PCR
at maternal fetuses/total amniocentesis. PCR also may be useful for demonstration of
infection,a weeks no. of fetuses (%) Sensitivity, % NPV, %
parasite DNA in fetal tissues and placenta [35].
6 0/14 (0) NA 100 Ultrasound. Ultrasound is recommended for women with
711 7/50 (14) 28.6 89.6 suspected or diagnosed acute infection acquired during or
1216 7/61 (11) 57.1 94.7
shortly before gestation. Ultrasound may reveal the presence
1721 14/66 (21) 92.9 98.1
of fetal abnormalities, including hydrocephalus, brain or he-
2226 16/36 (44) 62.5 76.9
patic calcifications, splenomegaly, and ascites [1].
2731 19/30 (63) 68.4 64.7
32 12/13 (92) 50 14.3 The clinical outcome of congenitally infected children whose
Total 75/270 (28) NA NA mothers had acquired the infection during the first trimester
of pregnancy, whose fetal ultrasound findings were normal, and
NOTE. The positive predictive value was 100%, regardless of gestational
age. Data are from [26]. NA, not applicable. who received spiramycin during gestation was recently re-
a
Maternal infection was diagnosed by seroconversion in the 270 women; ported. Although these children were expected to have severe
261 (97%) were given treatment with spiramycin.
b
Congenital infection was diagnosed by the persistence of Toxoplasma IgG
damage (table 1), their 2-year follow-up revealed that their
antibodies after 1 year of life. outcomes did not differ significantly from those of infected

560 CID 2008:47 (15 August) CLINICAL PRACTICE

children born to mothers who had acquired the infection dur- ramycin is teratogenic (table 6). The drug is administered until
ing the second and third trimesters (table 1) [36]. The authors delivery even in those patients with negative results of amniotic
concluded that, in such circumstances, termination of preg- fluid PCR, because of the theoretical possibility that fetal in-
nancy was not indicated. However, appropriate treatment was fection can occur later in pregnancy from a placenta that was
essential, and prenatal ultrasound findings should be free of infected earlier in gestation [42]. For pregnant women in whom
any anomaly [36]. In addition to ultrasound, CT has been used the possibility of fetal infection is high or fetal infection has
to search for brain calcifications, and MRI for other abnor- been established, treatment with spiramycin should be switched
malities in the fetus. after the 18th week of gestation to treatment with pyrime-
Histological analysis and attempts to isolate the parasite. thamine, sulfadiazine, and folinic acid. In some centers, change
Occasionally, placental or fetal tissues from pregnant women to such treatment occurs earlier (e.g., at 1416 weeks of ges-
suspected of having acquired acute infection during gestation tation) [38].
are available to attempt to determine whether vertical trans- Spiramycin is not commercially available in the United
mission of the parasite has occurred. T. gondii cysts may be States. It can be obtained at no cost and after consultation
visualized in these tissues with the Wright-Giemsa stain, but (with PAMF-TSL, telephone number (650) 853-4828, or the
immunoperoxidase staining using T. gondiispecific antibodies US [Chicago, IL] National Collaborative Treatment Trial Study
is more sensitive [37]. Isolation of the parasite can be attempted [NCCTS], telephone number (773) 834-4152) through the US
by inoculation of tissues into tissue culture or mice [1]. Food and Drug Administration, telephone number (301) 796-
1600. It is administered orally at a dosage of 1.0 g (or 3 million
APPROACH FOR PATIENTS WITH SUSPECTED U) every 8 h (total dosage of 3 g or 9 million U per day).
OR DIAGNOSED T. GONDII INFECTION Through this program, Sanofi-Aventis, for many years, has
ACQUIRED DURING GESTATION kindly been providing spiramycin to pregnant women in the
United States at no cost.
Once it has been established that serological test results are
consistent with a recently acquired infection and that acqui- In recent years, the effectiveness of spiramycin to prevent
sition of the infection during the first 18 weeks of gestation or congenital toxoplasmosis has become controversial [38, 43].
shortly before conception cannot be excluded, an attempt to Members of the European Multicentre Study on Congenital
prevent vertical transmission of the parasite through treatment Toxoplasmosis (EMSCOT) have raised the question as to the
with spiramycin is recommended for the mother by many in- value of such treatment [38, 43]. These investigators have stated
vestigators in the United States and Europe (figure 3). If fetal repeatedly that carefully designed studies are necessary to clarify
infection is confirmed by a positive result of PCR of amniotic whether spiramycin is efficacious in prevention of congenital
fluid at 18 weeks of gestation or later, treatment with pyri- toxoplasmosis. We agree with that specific statement. Recent
methamine, sulfadiazine, and folinic acid is recommended (if data from the EMSCOT investigators suggest that spiramycin
the patient is already receiving spiramycin, the recommenda- may be more efficacious when administered early after sero-
tion is to switch to this combination). In some centers in Eu- conversion [43]. The studies supporting both positions (for
rope, this switch takes place as early as week 1416 [38]. and against the recommendation of spiramycin treatment) pri-
Because of the high transmission rates observed after 18 marily suffer from a lack of randomization and necessary con-
weeks of gestation, treatment with pyrimethamine, sulfadiazine, trols in their design and from small sample sizes for the group
and folinic acid is also used for patients who have acquired the of untreated women [30, 3843]. The data provided to date
infection after 18 weeks of gestation, in an attempt to prevent have not ruled out a potential benefit from spiramycin [44].
fetal infection from occurring and, if transmission has occurred, It has been suggested, and we agree, that only a large, random-
to provide treatment for the fetus (figure 3). Pyrimethamine is ized, controlled clinical trial would provide clinicians and pa-
not used earlier because it is potentially teratogenic. tients with valid evidence of the potential benefit of prenatal
Spiramycin. The use of the macrolide antibiotic spira- treatment with spiramycin [43]. Until there is further clarifi-
mycin has been reported to decrease the frequency of vertical cation on this subject, we continue to recommend spiramycin
transmission [30, 3942]. However, carefully designed, pro- treatment for women with suspected or confirmed acute T.
spective studies that demonstrate this effect have not been per- gondii infection acquired during the first 18 weeks of gestation
formed. The protection has been reported to be more distinct [1].
in women infected during their first trimester [39, 40, 42]. In Pyrimethamine, sulfadiazine, and folinic acid. Until fur-
studies using historical controls, the incidence of congenital ther information is available, we consider it justifiable to rec-
infection was reduced by 60% [39, 40, 42]. Spiramycin does ommend the combination of pyrimethamine, sulfadiazine, and
not readily cross the placenta and thus is not reliable for treat- folinic acid as treatment for pregnant women who acquire the
ment of infection in the fetus. There is no evidence that spi- infection after 18 weeks of gestation and for those in whom

CLINICAL PRACTICE CID 2008:47 (15 August) 561

Figure 3. Approach for pregnant women who are suspected or confirmed to have toxoplasmosis acquired during gestation. 1Consultation with a
reference laboratory or physician expert in toxoplasmosis is suggested (i.e., Palo Alto Medical Foundation Toxoplasma Serology Laboratory, telephone
number (650) 853-4828, or US [Chicago, IL] National Collaborative Treatment Trial Study, telephone number (773) 834-4152). 2Gestational age at which
maternal infection was suspected or confirmed to have been acquired (or the best estimate); this is not the gestational age at which the patient
consulted with or was seen by the health care provider. 3For dosages and comments, see table 6. Folic acid should not be used as a substitute for
folinic acid. wks, Weeks.

fetal infection has been confirmed (i.e., by positive result of APPROACH FOR OTHERWISE
amniotic fluid PCR) or is highly suspected (e.g., because of IMMUNOCOMPETENT PATIENTS WITH
fetal abnormalities consistent with congenital toxoplasmosis de- T. GONDII INFECTION MOST LIKELY
tected by ultrasound examination) (table 6) [1, 45]. This drug ACQUIRED 6 MONTHS BEFORE GESTATION
regimen is used in an attempt to treat the infection in the fetus
Because the incidence of congenital toxoplasmosis in the off-
and, in some instances, with the hope of preventing transmis-
spring of women who are known to have been infected before
sion, especially in those women for whom amniocentesis for
gestation or whose serological test results reveal infection ac-
PCR testing cannot be performed and whose infection was
quired in the distant past (before gestation) has been shown
acquired after 18 weeks of gestation [46]. Pyrimethamine is
to be extremely low (approaching zero), use of treatment with
potentially teratogenic and should not be used in the first tri-
spiramycin or with pyrimethamine, sulfadiazine, and folinic
mester of pregnancy. The drug produces reversible, usually
acid and prenatal diagnosis of fetal infection are not indicated
gradual, dose-related depression of the bone marrow. All pa-
unless the mother is immunocompromised.
tients who receive pyrimethamine should have complete blood
cell counts frequently monitored. Folinic acid (not folic acid)
APPROACH FOR IMMUNOCOMPROMISED
is used for reduction and prevention of the hematological tox-
PATIENTS WITH T. GONDII INFECTION
icities of the drug.
ACQUIRED BEFORE GESTATION
We suggest that each case involving a pregnant woman sus-
pected of having or given the diagnosis of acute T. gondii in- Women who are coinfected with HIV and T. gondii and who
fection acquired during gestation be discussed with an expert have developed AIDS are at risk of reactivating their T. gondii
in the management of toxoplasmosis (in the United States, e.g., infection, developing severe toxoplasmosis (i.e., toxoplasmic
PAMF-TSL or NCCTS). encephalitis, pneumonia, etc.), and/or transmitting the parasite

562 CID 2008:47 (15 August) CLINICAL PRACTICE

 Table 7. Measures to prevent primary Toxoplasma gondii infection during pregnancy.

Prevention measures
Cook meat to well done or thoroughly to 67C (153F). Meat should not be pink in the center.
Note that meat that is smoked, cured in brine, or dried may still be infectious
Avoid mucous membrane contact when handling raw meat
Wash hands carefully after contact with raw meat
Kitchen surfaces and utensils that have come in contact with raw meat should be washed wearing gloves
Refrain from skinning or butchering animals
Avoid contact with materials potentially contaminated with cat feces, especially when handling cat litter or gardening.
Wearing gloves is recommended when these activities cannot be avoided.
Disinfect emptied cat-litter box with near-boiling water for 5 min before refilling
Wash fruits and vegetables before consumption
Avoid drinking water potentially contaminated with oocysts

to their offspring [1, 11]. Fortunately, such transmission is fected before gestation and who do not have active ocular tox-
surprisingly rare [1, 11]. At present, data are insufficient to oplasmosis [10]. Those with toxoplasmic chorioretinitis, con-
define the effectiveness of treatment intended to prevent vertical sidered to be a manifestation of recently acquired infection [47],
transmission of T. gondii in an HIV-infected woman. Until should be given treatment for the infection, for both the eye
more data become available, we suggest that Toxoplasma-se- disease and the risk of transmission of the infection to their
ropositive pregnant women whose CD4 cell count is !200 cells/ fetus. In this scenario, the reader is referred to the approach
mm3 receive trimethoprim-sulfamethoxazole (80 mg trimeth- described above in the Approach for Patients with Suspected
oprim and 400 mg sulfamethoxazole in a single-strength tablet, or Diagnosed T. gondii Infection Acquired during Gestation
1 tablet per day; this treatment is commonly used to prevent section.
Pneumocystis pneumonia in such patients) in an attempt to
prevent both reactivation of their Toxoplasma infection and APPROACH FOR PATIENTS WITH RECENTLY
transmission of the parasite to their offspring. Trimethoprim ACQUIRED T. GONDII INFECTION WHO WANT
is usually avoided in the first trimester, because it is a folic acid TO KNOW WHEN IT IS SAFE TO BECOME
antagonist. For women whose CD4 cell count is 1200 cells/ PREGNANT
mm3 and for nonHIV infected, immunocompromised
After a nonpregnant woman of childbearing age receives a di-
women, spiramycin treatment is suggested for the duration of
agnosis of a recently acquired T. gondii infection, the question
the pregnancy. Unfortunately, there are no studies to determine
frequently arises as to when they can safely become pregnant,
whether these strategies are effective.
with regard to the risk of congenital transmission of the par-
Performance of amniotic fluid PCR may not be advisable
asite. It should be understood that there are no definitive data
for HIV-infected women because of the risk of facilitating the
on this subject. Our advice has been conservative; we recom-
transmission of HIV to the fetus during the procedure. Am-
mend that such women wait 6 months (from the date that the
niotic fluid PCR should be considered for nonHIV infected,
acute infection was diagnosed or documented) before attempt-
immunocompromised pregnant women who are chronically
infected with T. gondii (as well as those who acquire the in- ing to become pregnant. Each case should be considered sep-
fection during pregnancy). Monthly ultrasound examinations arately and, preferably, in consultation with an expert.
should be considered as well for all immunocompromised preg-
nant women chronically infected with T. gondii. PREVENTION

Primary prevention. Educational materials that contain mes-

APPROACH FOR PREGNANT WOMEN WITH
sages on how to prevent pregnant women from becoming in-
TOXOPLASMIC CHORIORETINITIS
fected have resulted in reduced rates of seroconversion (table
Pregnant women given a diagnosis of toxoplasmic chorioretin- 7) [4850]. Educational measures should be in written form
itis should have serological evaluation to establish whether the (e.g., books, magazines, or simple handouts), available in dif-
infection was acquired recently or in the distant past. Pregnant ferent languages, and integrated into existing prenatal pro-
women with toxoplasmic chorioretinitis as a result of reacti- grams, visits, and classes. Ultimately, it is the responsibility of
vation of a latent infection (acquired before gestation) do not health care policy makers and physicians to educate both preg-
appear to have a higher risk for transmission of the parasite nant women and women who are considering becoming preg-
to their offspring than that of pregnant women who were in- nant, with regard to preventive measures. The need to take

CLINICAL PRACTICE CID 2008:47 (15 August) 563

Table 6. Medicines used for pregnant women who have suspected or confirmed Toxoplasma gondii infection acquired during gestation.

Treatment Dosage Comments

Spiramycin 1 g (3 million U) every 8 h (for a total Not teratogenic; does not treat infection in the fetus; indicated for pregnant women
of 3 g or 9 million U per day) suspected of having acquired the infection at !18 weeks of gestation. Spiramycin
treatment should be continued until delivery in women with low suspicion of fe-
tal infection or those with documented negative results of amniotic fluid PCR and
negative findings on ultrasounds at follow-up. Available in the United States only
through the Investigational New Drug process at the FDA. Prior consultation with
a
medical consultants is required.
Pyrimethamine, sulfadiazine, Pyrimethamine: 50 mg every 12 h for Pyrimethamine is teratogenic; therefore, this combination should not be used be-
and folinic acid 2 days followed by 50 mg daily; fore week 18 of gestation (in some centers in Europe, it is used as early as
sulfadiazine: initial dose of 75 mg/ week 1416). Indicated for women suspected of having acquired infection at
kg, followed by 50 mg/kg every 12 18 weeks of gestation and those with documented fetal infection (positive re-
b
h (maximum, 4 g/day); folinic acid sult of amniotic fluid PCR) or abnormal ultrasound findings suggestive of congeni-
(leucovorin): 1020 mg daily (during tal toxoplasmosis, given when patient is at 18 weeks of gestation
and 1 week after completion of
pyrimethamine therapy)

NOTE. FDA, US Food and Drug Administration.

a
Palo Alto Medical Foundation Toxoplasma Serology Laboratory, telephone number (650) 853-4828, or US (Chicago, IL) National Collaborative Treatment Trial
Study, telephone number (773) 834-4152.
b
Folic acid should not be used as a substitute for folinic acid.

these preventive measures continually must be reinforced trimester but who have not yet formed antibodies, as well as
throughout pregnancy for seronegative women. [48, 51]. Table infants infected early in gestation who are negative for IgM and
7 lists the measures that can be taken in an attempt to prevent IgA antibodies. Postnatal screening programs do not allow for
T. gondii infection. Physicians are urged to make such written measures that attempt to prevent congenital infection.
information available to their pregnant patients. Written ma-
terials are available through the March of Dimes and in a free, Acknowledgments
downloadable format at http://www.toxoplasmosis.org/. Potential conflicts of interest. J.G.M. is director and J.S.R. is founder
Most important is to inform these women that all meat be of and consultant for the Palo Alto Medical Foundation Toxoplasma Se-
prepared well done (not pink in the center). Meat should rology Laboratory.
be heated throughout to at least 67C (153F). Freezing to at
least 20C (4F) for 24 h and thawing also kills T. gondii References
cysts [3, 52]. The process of curing meat does not necessarily 1. Remington JS, McLeod R, Thuilliez P, Desmonts G. Toxoplasmosis.
result in a product free of parasite cysts [53]. In: Remington JS, Klein JO, Wilson CB, Baker C, eds. Infectious dis-
Secondary prevention (serological screening). In addition eases of the fetus and newborn infant. 6th ed. Philadelphia: Elsevier
Saunders, 2006:9471091.
to implementation of primary preventive measures in sero- 2. Roberts T, Frenkel JK. Estimating income losses and other preventable
negative women, it is important to identify those women who costs caused by congenital toxoplasmosis in people in the United States.
acquire T. gondii infection during gestation, and if fetal infection J Am Vet Med Assoc 1990; 196:24956.
3. Dubey JP, Hill DE, Jones JL, et al. Prevalence of viable Toxoplasma
is detected by prenatal testing, therapeutic options, including
gondii in beef, chicken, and pork from retail meat stores in the United
termination of pregnancy and antibiotic treatment of the fetus States: risk assessment to consumers. J Parasitol 2005; 91:108293.
in utero, should be discussed with the patient. Women and 4. Bowie WR, King AS, Werker DH, et al. Outbreak of toxoplasmosis
their partners have the right to know whether their fetus is at associated with municipal drinking water. Lancet 1997; 350:1737.
5. Miller MA, Gardner IA, Kreuder C, et al. Coastal freshwater runoff is
risk for congenital toxoplasmosis or whether their fetus has a risk factor for Toxoplasma gondii infection of southern sea otters
already been infected. Congenital toxoplasmosis will continue (Enhydra lutris nereis). Int J Parasitol 2002; 32:9971006.
to go largely undiagnosed in the United States in the absence 6. Bahia-Oliveira LM, Jones JL, Azevedo-Silva J, Alves CC, Orefice F,
Addiss DG. Highly endemic, waterborne toxoplasmosis in north Rio
of universal screening programs to detect acute T. gondii in- de Janeiro state, Brazil. Emerg Infect Dis 2003; 9:5562.
fection acquired during gestation and in the absence of effective 7. de Moura L, Bahia-Oliveira LM, Wada MY, et al. Waterborne toxo-
and more widely distributed educational programs [1, 9, 54]. plasmosis, Brazil, from field to gene. Emerg Infect Dis 2006; 12:3269.
8. Lin YL, Liao YS, Liao LR, Chen FN, Kuo HM, He S. Seroprevalence
As an alternative, in the states of Massachusetts, New Hamp-
and sources of Toxoplasma infection among indigenous and immigrant
shire, and Vermont, a secondary prevention program that per- pregnant women in Taiwan. Parasitol Res 2008; published online Mar
forms Toxoplasma serological testing in all newborns has been 8.
underway for several years [55, 56]. Although postnatal screen- 9. Boyer KM, Holfels E, Roizen N, et al. Risk factors for Toxoplasma
gondii infection in mothers of infants with congenital toxoplasmosis:
ing of newborns identifies some subclinically infected infants, implications for prenatal management and screening. Am J Obstet
it has the potential to miss those infected late in the third Gynecol 2005; 192:56471.

564 CID 2008:47 (15 August) CLINICAL PRACTICE

10. Garweg JG, Scherrer J, Wallon M, Kodjikian L, Peyron F. Reactivation of fetal infection with Toxoplasma gondii. Am J Obstet Gynecol
of ocular toxoplasmosis during pregnancy. BJOG 2005; 112:2412. 2004; 190:797802.
11. Mitchell CD, Erlich SS, Mastrucci MT, Hutto SC, Parks WP, Scott GB. 32. Costa JM, Darde ML, Assouline B, Vidaud M, Bretagne S. Microsatellite
Congenital toxoplasmosis occurring in infants perinatally infected with in the beta-tubulin gene of Toxoplasma gondii as a new genetic marker
human immunodeficiency virus 1. Pediatr Infect Dis J 1990; 9:5128. for use in direct screening of amniotic fluids. J Clin Microbiol 1997;
12. Remington JS, McLeod R, Desmonts G. Toxoplasmosis. In: Remington 35:25425.
JS, Klein JO, eds. Infectious diseases of the fetus and newborn infant. 33. Chabbert E, Lachaud L, Crobu L, Bastien P. Comparison of two widely
4th ed. Philadelphia: W. B. Saunders, 1995:140267. used PCR primer systems for detection of Toxoplasma in amniotic
13. Wechsler B, Le Thi Huong D, Vignes B, Piette JC, Chomette G, Godeau fluid, blood, and tissues. J Clin Microbiol 2004; 42:171922.
P. Toxoplasmose et lupus: revue de la litterature a propos de 4 obser- 34. Bretagne S. Molecular diagnostics in clinical parasitology and mycol-
vations. Ann Med Interne (Paris) 1986; 137:32430. ogy: limits of the current polymerase chain reaction (PCR) assays and
14. Dunn D, Wallon M, Peyron F, Petersen E, Peckham C, Gilbert R. interest of the real-time PCR assays. Clin Microbiol Infect 2003; 9:
Mother-to-child transmission of toxoplasmosis: risk estimates for clin- 50511.
ical counselling. Lancet 1999; 353:182933. 35. Fricker-Hidalgo H, Brenier-Pinchart MP, Schaal JP, Equy V, Bost-Bru
15. Montoya JG. Laboratory diagnosis of Toxoplasma gondii infection and C, Pelloux H. Value of Toxoplasma gondii detection in one hundred
toxoplasmosis. J Infect Dis 2002; 185(Suppl 1):S7382. thirty-three placentas for the diagnosis of congenital toxoplasmosis.
16. Liesenfeld O, Press C, Montoya JG, et al. False-positive results in im- Pediatr Infect Dis J 2007; 26:8456.
munoglobulin M (IgM) toxoplasma antibody tests and importance of 36. Berrebi A, Bardou M, Bessieres MH, et al. Outcome for children in-
confirmatory testing: the Platelia Toxo IgM test. J Clin Microbiol fected with congenital toxoplasmosis in the first trimester and with
1997; 35:1748. normal ultrasound findings: a study of 36 cases. Eur J Obstet Gynecol
17. Public Health Service, Department of Health and Human Services; US Reprod Biol 2007; 135:537.
Food and Drug Administration. FDA public health advisory: limita- 37. Conley FK, Jenkins KA, Remington JS. Toxoplasma gondii infection of
tions of toxoplasma IgM commercial test kits. Rockville, MD: De- the central nervous system: use of the peroxidase-antiperoxidase
partment of Health and Human Services; US Food and Drug Admin- method to demonstrate Toxoplasma in formalin fixed, paraffin em-
istration, 1997:3. bedded tissue sections. Hum Pathol 1981; 12:6908.
18. Wilson M, Remington JS, Clavet C, et al. Evaluation of six commercial 38. Gilbert R, Gras L, European Multicentre Study on Congenital Toxo-
kits for detection of human immunoglobulin M antibodies to Toxo- plasmosis. Effect of timing and type of treatment on the risk of mother
plasma gondii. J Clin Microbiol 1997; 35:31125. to child transmission of Toxoplasma gondii. BJOG 2003; 110:11220.
19. Liesenfeld O, Montoya JG, Tathineni NJ, et al. Confirmatory serologic 39. Desmonts G, Couvreur J. Congenital toxoplasmosis: a prospective
testing for acute toxoplasmosis and rate of induced abortions among study of the offspring of 542 women who acquired toxoplasmosis
women reported to have positive Toxoplasma immunoglobulin M an- during pregnancy. In: Thalhammer O, Pollak A, Baumgarten K, eds.
tibody titers. Am J Obstet Gynecol 2001; 184:1405. Perinatal medicine: proceedings of the 6th European Congress, Vienna.
20. Lappalainen M, Hedman K. Serodiagnosis of toxoplasmosis: the impact Stuttgart, Germany: Georg Thieme Publishers, 1979:5160.
of measurement of IgG avidity. Ann Ist Super Sanita 2004; 40:818. 40. Forestier F. Les foetopathies infectieuses: prevention, diagnostic pre-
21. Roberts A, Hedman K, Luyasu V, et al. Multicenter evaluation of strat- natal, attitude pratique. Presse Med 1991; 20:144854.
egies for serodiagnosis of primary infection with Toxoplasma gondii. 41. Hohlfeld P, Daffos F, Thulliez P, et al. Fetal toxoplasmosis: outcome
Eur J Clin Microbiol Infect Dis 2001; 20:46774. of pregnancy and infant follow-up after in utero treatment. J Pediatr
22. Hedman K, Lappalainen M, Seppala I, Makela O. Recent primary 1989; 115:7659.
Toxoplasma infection indicated by a low avidity of specific IgG. J Infect 42. Couvreur J, Desmonts G, Thulliez P. Prophylaxis of congenital toxo-
Dis 1989; 159:7369. plasmosis: effects of spiramycin on placental infection. J Antimicrob
23. Lappalainen M, Koskela P, Koskiniemi M, et al. Toxoplasmosis acquired Chemother 1988; 22:193200.
during pregnancy: improved serodiagnosis based on avidity of IgG. J 43. Thiebaut R, Leproust S, Chene G, Gilbert R. Effectiveness of prenatal
Infect Dis 1993; 167:69197. treatment for congenital toxoplasmosis: a meta-analysis of individual
24. Pelloux H, Brun E, Vernet G, et al. Determination of antiToxoplasma patients data. Lancet 2007; 369:11522.
gondii immunoglobulin G avidity: adaptation to the Vidas system 44. Thulliez P. Commentary: efficacy of prenatal treatment for toxoplas-
(bioMerieux). Diagn Microbiol Infect Dis 1998; 32:6973. mosis: a possibility that cannot be ruled out. Int J Epidemiol 2001;
25. Lappalainen M, Koskiniemi M, Hiilesmaa V, et al. Outcome of children 30:13156.
after maternal primary Toxoplasma infection during pregnancy with 45. Kieffer F, Wallon M, Garcia P, Thulliez P, Peyron F, Franck J. Risk
emphasis on avidity of specific IgG. Pediatr Infect Dis J 1995; 14: factors for retinochoroiditis during the first 2 years of life in infants
35461. with treated congenital toxoplasmosis. Pediatr Infect Dis J 2008; 27:
26. Romand S, Wallon M, Franck J, Thulliez P, Peyron F, Dumon H. 2732.
Prenatal diagnosis using polymerase chain reaction on amniotic fluid 46. Foulon W, Villena I, Stray-Pedersen B, et al. Treatment of toxoplasmosis
for congenital toxoplasmosis. Obstet Gynecol 2001; 97:296300. during pregnancy: a multicenter study of impact on fetal transmission
27. Montoya JG, Huffman HB, Remington JS. Evaluation of the immu- and childrens sequelae at age 1 year. Am J Obstet Gynecol 1999; 180:
noglobulin G avidity test for diagnosis of toxoplasmic lymphadenop- 4105.
athy. J Clin Microbiol 2004; 42:462731. 47. Montoya JG, Remington JS. Toxoplasmic chorioretinitis in the setting
28. Montoya JG, Liesenfeld O, Kinney S, Press C, Remington JS. VIDAS of acute acquired toxoplasmosis. Clin Infect Dis 1996; 23:27782.
test for avidity of Toxoplasma-specific immunoglobulin G for confir- 48. Foulon W, Naessens A, Lauwers S, De Meuter F, Amy JJ. Impact of
matory testing of pregnant women. J Clin Microbiol 2002; 40:25048. primary prevention on the incidence of toxoplasmosis during preg-
29. Grover CM, Thulliez P, Remington JS, Boothroyd JD. Rapid prenatal nancy. Obstet Gynecol 1988; 72:3636.
diagnosis of congenital Toxoplasma infection by using polymerase chain 49. Baril L, Ancelle T, Goulet V, Thulliez P, Tirard-Fleury V, Carme B. Risk
reaction and amniotic fluid. J Clin Microbiol 1990; 28:2297301. factors for Toxoplasma infection in pregnancy: a case-control study in
30. Hohlfeld P, Daffos F, Costa J-M, Thulliez P, Forestier F, Vidaud M. France. Scand J Infect Dis 1999; 31:3059.
Prenatal diagnosis of congenital toxoplasmosis with polymerase-chain- 50. Gollub EL, Leroy V, Gilbert R, Chene G, Wallon M. Effectiveness of
reaction test on amniotic fluid. N Engl J Med 1994; 331:6959. health education on Toxoplasma-related knowledge, behaviour, and risk
31. Romand S, Chosson M, Franck J, et al. Usefulness of quantitative of seroconversion in pregnancy. Eur J Obstet Gynecol Reprod Biol
polymerase chain reaction in amniotic fluid as early prognostic marker 2008; 136:13745.

CLINICAL PRACTICE CID 2008:47 (15 August) 565

51. Wong S, Remington JS. Toxoplasmosis in pregnancy. Clin Infect Dis 54. McCabe R, Remington JS. Toxoplasmosis: the time has come. N Engl
1994; 18:85362. J Med 1988; 318:3135.
52. Dubey JP, Lindsay DS, Speer CA. Structures of Toxoplasma gondii tach- 55. Schmidt DR, Hogh B, Andersen O, Fuchs J, Fledelius H, Petersen E.
yzoites, bradyzoites, and sporozoites and biology and development of The national neonatal screening programme for congenital toxoplas-
tissue cysts. Clin Microbiol Rev 1998; 11:26799. mosis in Denmark: results from the initial four years, 19992002. Arch
53. Geurina NG, Hsu HW, Meissner HC, et al.; New England Regional Dis Child 2006; 91:6615.
Toxoplasma Working Group. Neonatal serologic screening and early 56. Guerina N, Hsu H-W, Meissner H, et al. Neonatal serologic screening
treatment for congenital Toxoplasma gondii infection. N Engl J Med and early treatment for congenital Toxoplasma gondii infection. N Engl
1994; 330:185863. J Med 1994; 330:185863.

566 CID 2008:47 (15 August) CLINICAL PRACTICE