Toxo Congentia Revis?o

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14 CME REVIEWARTICLE Volume 56, Number 5

OBSTETRICAL AND GYNECOLOGICAL SURVEY


Copyright 2001
by Lippincott Williams & Wilkins, Inc.

CHIEF EDITORS NOTE: This article is the 14th of 36 that will be published in 2001 for which a total of up to 36 Category 1
CME credits can be earned. Instructions for how credits can be earned appear on the last page of the Table of Contents.

Congenital Toxoplasmosis: A Review


Jeffrey L. Jones, MD, MPH,* Adriana Lopez, MHS,
Marianna Wilson, MS, Jay Schulkin, PhD and Ronald Gibbs, MD
*Medical Epidemiologist, Epidemiologist, and Chief, Reference Immunodiagnostic Laboratory, Division of
Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia; and Director of Research, American College of Obsetricians and Gynecologists,
Washington, DC, and Professor and Chairman of Obstetrics and Gynecology, University of Colorado Health
Sciences Center, Denver, Colorado

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. In the United
States, approximately 85% of women of childbearing age are susceptible to acute infection with T.
gondii. Acute infections in pregnant women may cause serious health problems when the organism is
transmitted to the fetus (congenital toxoplasmosis), including mental retardation, seizures, blindness,
and death. An estimated 400 to 4000 cases of congenital toxoplasmosis occur in the U.S. each year.
Manifestations of congenital toxoplasmosis may not become apparent until the second or third decade
of life. Serologic tests are used to diagnose acute infection in pregnant women, but false-positive tests
occur frequently, therefore, serologic diagnosis must be confirmed at a reference laboratory before
treatment with potentially toxic drugs should be considered. Much of congenital toxoplasmosis can be
prevented by educating women of childbearing age and pregnant women to avoid eating raw or
undercooked meat, to avoid cross-contamination of other foods with raw or undercooked meat, and to
use proper cat-litter and soil-related hygiene.
Target Audience: Obstetricians & Gynecologists, Family Physicians
Learning Objectives: After completion of this article, the reader will be able to outline the biology of
toxoplasmosis, to explain the methods of transmission of toxoplasmosis, and to identify the methods
used to diagnose toxoplasmosis in pregnancy.

Toxoplasmosis is caused by infection with the pro- toxoplasmosis) and cause severe sequelae in the infant
tozoan parasite Toxoplasma gondii. In the United including mental retardation, blindness, and epilepsy.
States, a serological survey from the Third National Practicing obstetricians may be confronted with a num-
Health and Nutrition Examination Survey found that ber of issues regarding toxoplasmosis, including diag-
an estimated 23% of adolescents and adults have nosis, laboratory testing, screening practices, clinical
laboratory evidence of infection with T. gondii (15% presentation, and prevention.
among women of childbearing age) (1; Centers for Although congenital toxoplasmosis is not a nationally
Disease Control, unpublished data, 1994). Although reportable disease, extrapolation from regional studies
these infections are usually either asymptomatic or as- indicates that an estimated 400 to 4,000 cases occur in
sociated with self-limited symptoms in adults (e.g., the U.S. each year (24). The most recent data from
fever, malaise, and lymphadenopathy), infections in New England indicate that congenital toxoplasmosis
pregnant women can cause serious health problems in occurs in approximately 1 in 10,000 live births (4).
the fetus if the parasites are transmitted (i.e., congenital
Reprint requests to: Jeffrey L. Jones, MD, MPH, Mailstop F-22, BIOLOGY, TRANSMISSION, CLINICAL
Centers for Disease Control and Prevention, 4770 Buford Highway SYMPTOMS, AND EPIDEMIOLOGY
NE, Atlanta, GE 30341-3724. Email: [email protected]
The authors have disclosed no significant financial or other T. gondii has a complex life cycle (Fig. 1) consist-
relationship with any commercial entity. ing of three stages: 1) tachyzoiteduring the acute
296
Congenital Toxoplasmosis Y CME Review Article 297

stage of infection, this form of the parasite invades inadequately cooked infected meat (especially pork,
and replicates within cells; 2) bradyzoiteduring mutton, and wild game meat (11)) or eat uncooked
latent infections, this form of the parasite is present foods that have come in contact with infected meat.
in tissue cysts; and 3) sporozoitethis form of the Second, humans can inadvertently ingest oocysts that
parasite is found in oocysts, which are environmen- cats have passed in their feces, either in a cat litter
tally resistant. T. gondii tachyzoites can invade and box or in soil (e.g., soil from gardening or unwashed
multiply in most cell types and are found in all fruits or vegetables). Third, a woman can transmit the
organs in acute infection, especially in muscle (in- infection to her unborn fetus transplacentally. In
cluding heart), liver, spleen, lymph nodes, and the adults, the incubation period ranges from 10 to 23
central nervous system. The tachyzoite is the form of days from ingestion of undercooked meat, and from
the organism responsible for congenital infection. 5 to 20 days from ingestion of oocysts from cat feces.
Cell invasion results in death of parasitized cells and A report conducted by the Economic Research
an acute inflammatory reaction. Placental lesions are Service of the United States Department of Agricul-
usually microscopic in humans, but macroscopic ne- ture concluded that one half of the toxoplasmosis
crosis has been reported in animals (5). cases in the U.S. are caused by eating contaminated
Members of the family Felidae (including domestic meat. The estimated economic burden of these infec-
and feral cats) are the definitive hosts of T. gondii. tions is $7.7 billion each year, primarily from con-
During acute infections, cats excrete unsporulated genital toxoplasmosis (12). Other data are available
(i.e., noninfectious) oocysts in their feces; after sev- to assist in estimating the portion of the disease
eral days to several weeks, depending on environ- burden of toxoplasmosis attributable to consumption
mental conditions, the oocysts sporulate and become of infected meat (i.e., raw or undercooked meat or
infectious. Under favorable conditions (i.e., in warm, cross-contamination from raw or undercooked meat).
moist soil), oocysts can remain infectious for approx- A recent study compared results from a cross-sec-
imately 1 year. They do not survive well in arid, cold tional seroprevalence study of Seventh Day Ad-
climates and can be destroyed by heating (610). ventists, a religious group that follows a diet contain-
Toxoplasmosis can be transmitted to humans by ing no meat, with serologic results from a control
three principal routes. First, humans can eat raw or group of volunteers who were not Seventh Day Ad-

Fig. 1. Life cycle of Toxoplasma gondii.


298 Obstetrical and Gynecological Survey

ventists (13). Results from this study documented a cleaning the cat litter box (26), eating raw or under-
significantly lower rate of Toxoplasma infection in cooked pork, mutton, lamb, beef, or mince meat
Seventh Day Adventists than the control group (24% products (24, 26, 27), gardening (25), eating raw or
vs. 50%, respectively; P .01). Thus, these data unwashed vegetables or fruits, eating raw vegetables
support the estimates that approximately one half of outside the home (24), contact with soil (27), wash-
T. gondii exposure is caused by eating infected meat. ing kitchen knifes infrequently (26), having poor
Of the 750 deaths attributed to toxoplasmosis each hand hygiene (24), and travel outside of Europe,
year, 375 (50%) are believed to be food-borne, mak- U.S., or Canada (27). Protective factors for T. gondii
ing toxoplasmosis the third leading microbial cause infection include a meat-free diet (13), living at high
of food-borne deaths in this country (salmonellosis altitudes and in arid climates (28, 29), and living in
and listeriosis are the first and second leading causes, climates with frequent freezing and thawing (30).
respectively) (14). Owning a cat has not been a consistent risk factor
Women infected with T. gondii before conception, for T. gondii infection. Owning a cat was not shown
with rare exception (15), do not transmit the infection to be a risk factor for T. gondii infection in two
to their fetuses. Women infected with T. gondii dur- studies of pregnant women (27, 31) and in a study of
ing pregnancy can transmit the infection across the HIV-infected persons (32). Risk for T. gondii infec-
placenta to their fetuses. The risk of congenital dis- tion does not occur from merely owning a cat, but
ease is lowest (1025%) when acute maternal infec- rather from being exposed to cat feces from a cat
tion occurs during the first trimester and highest shedding oocysts. Cats generally only shed oocysts
(6090%) when acute maternal infection occurs dur- for several weeks during their lives if they become
ing the third trimester (10, 16, 17). However, the infected with T. gondii. Cats kept indoors that do not
severity of disease is worse if infection is acquired in hunt prey or are not fed raw meat are not likely to
the first trimester (10, 18). The overall risk of con- acquire T. gondii infection and, therefore, pose little
genital infection from acute T. gondii infection dur- risk. Unless cats are sick with diarrhea, little or no
ing pregnancy is 20% to 50%.
feces will stick to their perianal area (11). Usually,
The classic triad of signs suggestive of congenital
adult cats are not diarrheal during the period in which
toxoplasmosis includes chorioretinitis, intracranial
they are shedding oocysts (11). Because of their
calcifications, and hydrocephalus. Most infants in-
grooming habits, fecal matter has not been found on
fected in utero are born with no obvious signs of
toxoplasmosis on routine examination, but up to 80% the fur of clinically normal cats (11). In addition, in
develop learning and visual disabilities later in life if a study of cats induced to shed oocysts, no oocysts
they are followed into adulthood (19, 20). If un- could be found on the cats fur after they shed oo-
treated, congenital toxoplasmosis can be associated cysts (33). Therefore, the possibility of transmission
with severe and even fatal disease (21). to human beings via touching cats is thought to be
In adults, the severity of T. gondii infection is minimal or nonexistent (11). Neighborhood or feral
correlated with the immune status of the infected cats that defecate in gardens or sandboxes may pose
person. Toxoplasmosis in immunocompetent adoles- the greatest risk for toxoplasmosis for some persons,
cents or adults is generally mild or inapparent. Mild whether or not they own a cat.
infections can result in lymphadenopathy, fever, fa- It should also be noted that because cats may not
tigue, and malaise, all of which usually resolve develop antibodies to T. gondii during the oocyst-
within weeks to months without specific treatment. shedding period, serologic examination of cats does
However, infection in immunocompromised persons not provide useful information regarding the ability
can be severe. Immunosuppression caused by AIDS of a particular cat to transmit toxoplasmosis (11). A
or therapies for malignancies, transplants, or lympho- cat that has a positive serologic test for T. gondii
proliferative disorders can result in reactivation of probably has shed oocysts previously and, therefore,
preexisting latent T. gondii infections. Reactivation may pose less of a risk than a serologically negative
most often involves the central nervous system, and cat, but cats can shed oocysts more that once, thus,
symptoms may include those of meningoencephalitis or serologic testing of cats is not really helpful in this
a mass lesion. Women with reactivated T. gondii infec- instance either.
tion can transmit the organism congenitally (22, 23). Outbreaks of toxoplasmosis in humans have been
Recent epidemiologic studies have identified the attributed to ingestion of raw or undercooked ground
following risk factors for T. gondii infection: owning beef, lamb, pork, venison (3439), unpasteurized
cats (24), seropositive cats in farming areas (25), goats milk (40), contaminated, unfiltered drinking
Congenital Toxoplasmosis Y CME Review Article 299

water (41, 42), soil exposure (43), and aerosolized


soil exposure (44).
High T. gondii seroprevalence is found in countries
such as France where undercooked meat is com-
monly eaten (45, 46), and in tropical areas of Latin
America or sub-Saharan Africa where cats are abun-
dant and the climate favors survival of oocysts (47
54). Studies in Scandinavian countries (5557) and
England (58) show lower seroprevalence, more sim-
ilar to that in the U.S.

DIAGNOSIS OF TOXOPLASMOSIS IN
PREGNANCY
Acute toxoplasmosis is diagnosed rarely by detect-
ing the parasite in body fluids, tissue, or secretions;
the most common method of diagnosis is based on
antibody detection. The presence of elevated levels
of Toxoplasma-specific IgG antibodies indicates in-
fection has occurred at some point, but does not
distinguish between an infection acquired recently
and one acquired in the distant past. In acute infec-
tion, IgG and IgM antibodies generally rise within 1
to 2 weeks of infection (59). Determining when T.
gondii infection occurred in a pregnant woman is
important because infection before conception poses
little risk for transmission of infection to the fetus;
however, infection after conception does pose such
risk. Detection of Toxoplasma-specific IgM antibod- Fig. 2. Algorithm for the serodiagnosis of toxoplasmosis in
ies has been used as an aid in determining the time of people older than 1 year of age. Adapted from Wilson M, McAuley
infection, but IgM antibodies have been reported to JM. Toxoplsama. In: Murray PR, Baron EJ, Pfaller MA et al., eds.
Manual of Clinical Microbiology, 7th Ed. Washington DC: ASM
persist for up to 18 months postinfection (6). A Press, 1999, pp 13471382.
negative IgM with a positive IgG result indicates
infection at least 1 year previously. A positive IgM
result may indicate more recent infection or may be ing these test limitations. The agency provided a
a false-positive reaction. A flow diagram for T. gon- guide for interpreting test results (Table 1) and issued
dii testing and guide to interpretation of T. gondii a recommendation to laboratory personnel and phy-
tests are presented in Figure 2 and Table 1. sicians advising them to be aware of the specificity
In the United States, commercial test kits for Tox- problems associated with some commercial test kits
oplasma-specific IgG and IgM antibodies are readily before making decisions about the clinical manage-
available. Some commercial IgM tests have had ment of their patients.
problems with specificity, resulting in unacceptably IgM-positive results should be confirmed by a Tox-
high rates of false-positive test results. In 1996, the oplasma reference laboratory (60). A toxoplasmosis
Food and Drug Administration (FDA) and Centers reference laboratory may be able to help narrow
for Disease Control (CDC) conducted extensive eval- down the time of infection with tests such as the IgG
uations of the six most commonly used commercial avidity test (61, 62). IgG avidity, or the strength with
IgM kits in the U.S. to determine the extent of the which IgG binds to T. gondii, usually shifts from low
problem with the specificity of these kits. Sensitivity avidity to high avidity at about 5 months after infec-
and specificity rates for these six kits ranged from tion and can be used to rule out primary T. gondii
93.3% to 100.0% and from 77.5% to 99.1%, respec- infection in early pregnancy in approximately three
tively (60). quarters of women with positive IgM serum tests
As a result of these findings, in 1997 FDA distrib- (61). Although commonly used in Europe, the IgG
uted an advisory to physicians in the U.S. highlight- avidity test is available currently in only two labora-
300 Obstetrical and Gynecological Survey

TABLE 1 Guide to general interpretation of Toxoplasma tion (AC/HS) test has also been useful in distinguish-
gondii serology results obtained with commercial assays ing recently acquired infections (63).
Results
Report/Interpretation for humans (except For identification of T. gondii intrauterine infec-
IgG IgM infants) tion, polymerase chain reaction (PCR) testing of am-
Negative Negative No serological evidence of infection with niotic fluid has allowed earlier testing than fetal
Toxoplasma. blood sampling (6468). In addition, PCR of amni-
Negative Equivocal Possible early acute infection or false- otic fluid is more sensitive than fetal blood sampling
positive IgM reaction. Obtain a new (69) and is safer. However, false-positive and false-
specimen for IgG and IgM testing. If
results for the second specimen re-
negative tests do occur with PCR (70). Because of
main the same, the patient is probably advances in PCR testing of amniotic fluid, cordocen-
not infected with Toxoplasma. tesis is indicated rarely today.
Negative Positive Possible acute infection or false-positive
IgM result. Obtain a new specimen for
IgG and IgM testing. If results for the SCREENING AND TREATMENT
second specimen remain the same,
the IgM reaction is probably a false- In France, a screening program was implemented
positive. in 1976 to detect and treat T. gondii infection during
Equivocal Negative Indeterminate: obtain a new specimen pregnancy. The goal of this program is to institute
for testing or retest this specimen for preventive measures for seronegative women and to
IgG in a different assay.
Equivocal Equivocal Indeterminate: obtain a new specimen
ensure early diagnosis and treatment of infection
for both IgG and IgM testing. acquired during pregnancy. Since the beginning of
Equivocal Positive Possible acute infection with Toxo- the program, premarital and prenatal medical exam-
plasma. Obtain a new specimen for inations for T. gondii antibodies have been per-
IgG and IgM testing. If results for the formed. Premarital examinations are conducted to
second specimen remain the same or
if the IgG becomes positive, both
distinguish previously infected women from women
specimens should be sent to a refer- who have not been previously infected. When an
ence laboratory with experience in the uninfected woman becomes pregnant, testing is con-
diagnosis of toxoplasmosis for further ducted at her first prenatal examination during her
testing. first trimester and at six additional examinations con-
Positive Negative Infected with Toxoplasma for 1 year.
Positive Equivocal Infected with Toxoplasma for probably
ducted monthly during her second and third trimes-
1 year, or false-positive IgM reac- ters. In addition, women are educated about preven-
tion. Obtain a new specimen for IgM tion methods during pregnancy (71). If these
testing. If results with the second screening tests detect evidence of acute infection
specimen remain the same, both during pregnancy, treatment for the woman is initi-
specimens should be sent to a refer-
ence laboratory with experience in the
ated with spiramycin in an effort to prevent transmis-
diagnosis of toxoplasmosis for further sion to the fetus. If infection in the fetus is confirmed
testing. through fetal blood sampling and amniocentesis, py-
Positive Positive Possible recent infection within the last rimethamine and sulfadiazine or sulfadoxine is added
12 months, or false-positive IgM reac- to the regimen (72, 73) because spiramycin does not
tion. Send the specimen to a refer-
ence laboratory with experience in the
generally cross the placenta.
diagnosis of toxoplasmosis for further Although the proportion of the population included
testing. in the French program has been incomplete, it has
been associated with a decline in the incidence of
congenital infection, as well as a decline in severe
disease detected at birth. The proportion of the de-
tories in the U.S.1 Confirmatory testing with a sero- cline specifically attributable to the program or to the
logic profile including the Sabin-Feldman dye test, general decline in Europe in rates of seropositivity is
IgM enzyme-linked immunosorbent assay (ELISA), difficult to determine because no unscreened group
IgA ELISA, IgE ELISA, and differential agglutina- of women exists for comparison.
1
Austria implemented a toxoplasmosis-screening
Editors Note: Toxoplasma Serology Laboratory, Research In- program in 1975. Nearly all women who become
stitute, Palo Alto Medical Foundation, Ames Building, 795 El
Camino Real, Palo Alto, CA 94301; phone: 650-853-4848, and
pregnant are serologically screened early in preg-
MRL Reference Laboratories, 5785 Corporate Ave., Cypress, CA nancy and, if the results are found to be negative
90630; phone: 800-445-0185. initially, are tested again during the second and third
Congenital Toxoplasmosis Y CME Review Article 301

trimesters. Women with T. gondii infections are treated alternatives for primary infections during pregnancy
as soon as infection is detected. Although seropositivity with the costs of no screening. With screening, the
rates among pregnant Austrian women have declined annual costs of congenital toxoplasmosis were
from approximately 50.0% during the late 1970s to U.S.$95 per pregnancy; without screening, annual
36.7% during the early 1990s, the incidence of congen- costs were U.S.$128 per pregnancy. Furthermore,
ital T. gondii infection has declined even more, from 50 screening along with health education was more ben-
to 70 cases per 10,000 births before the program to 1 eficial than health education alone (76). The study
per 10,000 births during the early 1990s (74). As with findings suggest screening is cost beneficial in coun-
the French program, the lack of an unscreened compar- tries with a low incidence of congenital toxoplasmo-
ison group precludes determining the proportion of the sis, such as Finland. The findings of other studies
decline attributable to the screening program, and the suggest screening programs can also be beneficial in
lack of cost figures precludes cost-effectiveness areas with high incidences of congenital toxoplasmo-
analyses. sis (72, 77, 78).
The European Research Network on Congenital Although the findings of some European studies
Toxoplasmosis was established in 1993 and has suggest T. gondii screening programs of women of
sponsored several studies regarding public health in- childbearing age can prevent cases of congenital
terventions for congenital toxoplasmosis. Most re- toxoplasmosis, several concerns limit support for
cently, a multicenter study was conducted to evaluate such programs in the U.S. Some researchers have
the effectiveness of toxoplasmosis treatment admin- argued that because the prevalence of congenital
istered during pregnancy in preventing transmission toxoplasmosis is so rare in the United States, acute
of maternal infection to the fetus. Pregnant women early pregnancy toxoplasmosis is far too uncommon
who visited one of five European university medical to warrant routine screening (79). The American
centers for prenatal care were screened for T. gondii College of Obstetricians and Gynecologists (ACOG)
antibodies at their first prenatal visit. Women who (80) does not recommend routine screening. Screen-
were seronegative were retested at least once every ing may lead to equivocal or false-positive test re-
trimester in two centers and monthly in the other sults (60, 77), which could lead to inappropriate
centers, until the birth of the infant. For women who treatment. There have been no randomized trials us-
seroconverted during pregnancy, prenatal antibiotic ing spiramycin or other medications to assess the
treatment was started, and their infants were fol- effect of treatment on congenital transmission. Au-
lowed for 1 year after birth. Treatment regimens thors conducting a review of studies performed from
consisted of spiramycin or a combination of py- 1966 through 1997 concluded that it is unclear
rimethamine and sulfadiazine. If prenatal infection whether antenatal treatment in women with toxoplas-
was confirmed with amniocentesis or cordocentesis, mosis reduces congenital transmission (81). In a mul-
women were treated with pyrimethamine and sulfa- ticenter evaluation of 144 pregnant women with
diazine or sulfadoxine. Of the women who screened acute toxoplasmosis in Europe, prenatal antibiotic
positive and did not receive prenatal therapy, trans- therapy had no impact on the maternal-fetal trans-
mission from mother to infant occurred in 72% of the mission rate. However, prenatal treatment reduced
mother-infant pairs; of women who received prenatal the rate of severe sequelae among infected infants
therapy, transmission occurred in 39% of the mother- from 20% to 3.5% (75). In their review of the liter-
infant pairs. However, this difference was not statis- ature, authors from Norway, a country with a low
tically significant when the time of gestation that T. incidence of toxoplasmosis similar to the U.S., con-
gondii infection occurred was accounted for in the cluded that sufficient scientific evidence is not yet
treated and untreated groups. Nevertheless, 20% of available to propose screening for toxoplasmosis in
the untreated mothers gave birth to infants with se- pregnant women (82). In addition, the Royal College
vere sequelae, whereas only 3.5% of the treated of Obstetricians and Gynecologists in the United
mothers gave birth to infants with severe sequelae. Kingdom has recommended that prenatal screening
Furthermore, the earlier antibiotics were adminis- for toxoplasmosis should not be introduced in the
tered after infection, the less likely sequelae were U.K. (83). Finally, researchers from the U.S. used
detected in the infant (75). decision analysis to evaluate clinical outcomes with
From January 1988 through June 1989, a cost- three alternatives: 1) no testing for congenital toxo-
benefit analysis of T. gondii screening during preg- plasmosis, 2) targeted screening in cases of inciden-
nancy was conducted in a prospective study in Fin- tal abnormalities noted on ultrasound, and 3) univer-
land. The study compared costs of screening sal serologic screening of pregnant women followed
302 Obstetrical and Gynecological Survey

by amniocentesis to diagnose fetal infection in cases still lead to at least 2.9 fetal losses per case of toxoplas-
of maternal seroconversion. Universal screening re- mosis avoided. Therefore, they concluded that screen-
duced the total number of cases of congenital toxo- ing of cat owners would probably not be appropriate. In
plasmosis compared with no testing or targeted a large well-designed study of acute T. gondii infection
screening. However, compared with no testing, uni- in pregnant women from the European Research Net-
versal screening with medical treatment resulted in work on congenital toxoplasmosis, none of the risk
18.5 additional pregnancy losses for each case of factors for T. gondii infection increased the risk by as
toxoplasmosis avoided (84). Risks associated with much as five-fold (27). Nevertheless, in this study, the
amniocentesis were an important factor (0.36% fetal highest risks were associated with eating undercooked
death rate). No cost assessment was done in this lamb or other less conventional meats that included
analysis. There is still a need for cost-effectiveness wild game meats and with travel outside Europe, U.S.,
studies to enable comparison of the benefits of ex- or Canada.
panded testing in the U.S., the costs of such testing, It would seem prudent to screen pregnant women
and the unintended adverse consequences that might for acute toxoplasmosis if there were suspicious ul-
accompany such testing. trasound findings. Such findings include hydroceph-
Side effects of treatments must be considered when alus, intracranial calcifications, microcephaly, fetal
treating pregnant women. Spiramycin is a macrolide growth restriction, ascites, and hepatosplenomegaly.
antibiotic that can cause gastrointestinal and dermato- In addition, HIV-infected women should be screened
logic reactions in the mother. The Medical Letter lists for toxoplasmosis (80).
spiramycin as the drug that should be used for toxo-
plasmosis for prophylactic use during pregnancy, how-
ever, it is an investigational drug in the U.S. and can PREVENTION OF TOXOPLASMOSIS IN
only be obtained through the manufacturer (85). Al- PREGNANT WOMEN
though sulfonamides have been associated with ker-
nicterus in the newborn when given in late pregnancy, Recommendations for prevention of toxoplasmosis in
this complication was not noted to occur in a review of pregnant women were discussed at a conference at the
screening programs by French authors (86). Py- Centers for Disease Control and Prevention and pub-
rimethamine is not generally recommended for preg- lished (71). These recommendations were as follows:
nant women because it is a folic acid antagonist (preg- To prevent toxoplasmosis and other food-borne
nancy category C). Folate serves as a coenzyme in the illnesses, food should be cooked to safe temper-
synthesis of DNA, RNA, myelin, and lipids. A lack of atures. A food thermometer should be used to
folic acid in pregnancy has been associated with neural measure the internal temperature of cooked meat
tube defects early in pregnancy before the neural tube to ensure that meat is cooked all the way
has closed. Screening programs do not generally rec- through. Beef, lamb, and veal roasts and steaks
ommend pyrimethamine and sulfadiazine treatment be- should be cooked to at least 145F; and pork,
fore 18 weeks gestation (10). Pyrimethamine has also ground meat, and wild game should be cooked
been associated with heart and kidney malformations in to 160F before eating. Whole poultry should be
infants and may increase the risk of central nervous cooked to 180F in the thigh to ensure that the
system cancer in childhood (87, 88). Pyrimethamine meat is cooked thoroughly.
and sulfadiazine also carry a risk of bone marrow sup- Fruits and vegetables should be peeled or
pression in both the mother and the infant (10). A washed thoroughly before eating.
supplement of folinic acid should be given with py- Cutting boards, dishes, counters, utensils, and
rimethamine to compensate for the reduction of folic hands should always be washed with hot soapy
acid caused by pyrimethamine. Unfortunately, because water after they have contacted raw meat, poul-
there are few cases available for study, it has not been try, seafood, or unwashed fruits or vegetables.
possible to fully assess the risks of side effects due to Pregnant women should wear gloves when gar-
treatment for toxoplasmosis during pregnancy. dening and during any contact with soil or sand
Much of the above discussion raises the issue of because cat waste might be in soil or sand. After
when targeted screening should be done for toxoplas- gardening or contact with soil or sand, hands
mosis in the U.S. In their decision analysis, Bader et al. should be washed thoroughly.
(84) determined that screening high risk women (de- Pregnant women should avoid changing cat lit-
fined as a five-fold increase in risk or a rate of maternal ter if possible. If no one else is available to
toxoplasmosis as high as 1 in 100 pregnancies) would change the cat litter, pregnant women should use
Congenital Toxoplasmosis Y CME Review Article 303

gloves, then wash hands thoroughly. The litter to1982, when no education measures were in effect.
box should be changed daily because T. gondii During 1983 to 1990, education sessions were pro-
oocysts require several days to become infec- vided to pregnant women. The intervention was as-
tious. Pregnant women should be encouraged to sociated with a 63% decrease in seroconversion rates
keep their cats inside and not adopt or handle (90). Although it is possible that other factors such as
stray cats. Cats should be fed only canned or a reduction of T. gondii infection in meat could be
dried commercial food or well-cooked table responsible for the reduction in seroconversion rates,
food, not raw or undercooked meats. this study suggests that educational intervention is
Health education for women of childbearing age beneficial in preventing acute toxoplasmosis among
should include information about meat-related pregnant women.
and soil-borne toxoplasmosis prevention. Educational programs are a potentially powerful
Healthcare providers should educate pregnant intervention because of their low cost, and because
women at their first prenatal visit about food pregnant women are motivated to protect the health
hygiene and prevention of exposure to cat feces. of their babies. However, the impact of educational
Healthcare providers who care for pregnant programs is difficult to evaluate because of the lim-
women should be educated about two potential ited number of comparative studies conducted with
problems associated with the T. gondii serology rigorous scientific methodology and of sufficient size
tests. First, no assay exists that can determine to enable calculation of the effectiveness of the in-
precisely when the initial T. gondii infection tervention compared with its cost.
occurred. Second, in populations with a low
incidence of T. gondii infection, such as in the
U.S., a substantial proportion of the positive AREAS FOR FUTURE RESEARCH
IgM test results will probably be false-positive. There is a need for more complete and accurate
The government and the meat industry should population-based data regarding the incidence of tox-
continue their efforts to reduce T. gondii in oplasmosis and the number of cases by mode of
meat. transmission. Development of techniques that would
One approach to preventing toxoplasmosis focuses enable tracing the source of individual infections to
on educating women of childbearing age about min- food-borne, cat-borne, or soil-borne transmission
imizing their risk for infection with T. gondii. Edu- would help in defining the best approaches for pre-
cational interventions assume that increased knowl- ventive education. Efforts are needed to develop
edge results in awareness, which consequently more accurate screening diagnostic tests and im-
results in changes in risky behavior and declines in proved confirmatory tests. Research is needed also to
infection rates. Messages emphasize the importance further determine the therapeutic value, costs, and
of avoiding eating raw or undercooked meat, han- benefits of prenatal toxoplasmosis screening. Genetic
dling raw meat safely, and washing hands after gar- research is underway to determine if specific strains
dening or changing the cat litter box. are more infectious or pathogenic to humans. It is
A study conducted as part of prenatal classes at already known that at least three clonal lineages of T.
Canadian public health agencies evaluated the effect gondii exist (91). It also may be possible with genetic
of a 10-minute teaching session on three behaviors: research to determine the source and spread of T.
practices associated with cleaning the cat litter box gondii infections in animals and humans. Finally,
and limiting the cats diet to cooked food; safe food- more research needs to be done on the most effective
handling practices; and hand washing after exposure means of primary prevention of toxoplasmosis
to cat feces, garden soil, or raw meats. Among through education.
women in the classes, behavior improved regarding
practices associated with cats; however, behavior
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