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Introduction:
Toxoplasmosis is caused by infection with the protozoan
parasite Toxoplasma gondii.
Toxoplasmosis can be transmitted to humans by three
principal routes.
First, humans can inadvertently ingest water or food
contaminated with oocysts that cats have passed in their
feces, either in a cat litter box or outdoors in soil.
This is the most common method of infection in
underdeveloped and developing countries. Epidemiologic
surveys have revealed that in most areas of the world,
the presence of cats is the primary importance for the
transmission of toxoplasmosis (1).
Second, humans can eat raw or inadequately cooked
infected meat or eat uncooked foods that have come in
contact with contaminated meat.
This is more common in developed countries where eating
undercooked meat is common.
Third, a woman can transmit the infection to her unborn
fetus.
Women infected with Toxoplasma before
conceptions, with rare exceptions such as
immunocompromised women or women infected shortly before
conception, do not transmit the infection to their
fetuses.
Women infected with Toxoplasma after conception
(i.e., during pregnancy) can transmit the infection
across the placenta to their fetuses.
Maternal infections early in pregnancy are less likely
to be transmitted to the fetus than infections later in
pregnancy, but early fetal infections, when they do
occur, are more likely than later infections to be
severe (2).
Although these infections are usually either
asymptomatic or associated with self-limited symptoms
(e.g., fever, malaise, and lymphadenopathy), infection
in immunosuppressed persons (e.g., persons with AIDS or
transplant patients) can be severe.
In addition, infections in pregnant women can cause
serious health problems in the fetus if the parasites
are transmitted (i.e., congenital toxoplasmosis) and
cause severe sequelae in the infant (e.g., mental
retardation, blindness, and epilepsy) (3).
Diagnosis
Acute infection is diagnosed by the isolation of T.
gondii , demonstration of tachyzoites in histologic
sections of tissue or cytologic preparations of body
fluids, serologic tests, or by amplification of T.
gondii DNA by PCR in blood or various body fluids.
The use of serologic tests to show specific antibody to
T. gondii is the primary method of diagnosis of
toxoplasma infections (4).
The problem with serologic diagnosis is that there is no
single test than can be used to support the diagnosis of
acute or chronic infection by T. gondii. In most
cases, a battery of tests is required to differentiate
between acute and chronic infections (4).
The presence of elevated levels of Toxoplasma-specific
IgG antibodies indicates infection has occurred at some
point but does not distinguish between an infection
acquired recently and one acquired in the distant past.
The presence of a high Toxoplasma-specific IgM
antibody titer combined with a high IgG titer probably
indicates an acute infection within the previous 3
months.
A low-to-medium IgM titer and a high IgG titer might
indicate an acute infection 3-6 months previously, but
IgM antibodies have been detected as long as 18 months
after initial infection (5) .
The most commonly used serologic tests for the diagnosis
of T. gondii infection are
Summarized in table1.
There are four groups of individuals in whom the
diagnosis of toxoplasmosis is most critical: pregnant
women who acquire their infection during gestation,
fetuses and newborns with congenital acquired infection,
immunocompromised patients, and patients with
chorioretinitis.
T. gondii infection in pregnancy:
Determining when T. gondii infection occurred in
a pregnant woman is particularly important because
infection before conception poses no substantial risk
for transmission of infection to the fetus; however,
infection after conception does pose such risk.
The
diagnosis of acute T. gondii infection in most
cases requires demonstration of either conversion from a
negative to a positive titer or a significant rise in
titers in serial serum samples obtained at least 3 weeks
apart.
However, using serum titers might not helpful if
considered late in the course of the patient’s pregnancy
because they may have reached their peak at the time the
first serum sample is obtained for testing.
Initial screening of maternal serum involves testing for
IgG and IgM antibodies.
The
lack of both IgG and IgM antibodies essentially excludes
active infection.
The
presence of IgG antibodies in the absence of IgM
antibodie in the first two trimesters amost always
indicate chronic maternal infection with no risk of
transmission to the fetus.
In
the third trimester, negative IgM antibodies with
positive IgG antibodies is most likely consistent with
chronic maternal infection but does not exclude entirely
the possibility of acute infection acquired early in
pregnancy.
In
these cases, the use other serologic testing such as IgA
or IgE antibodies may be of particular help (6).
However, a positive IgM test result requires further
assessment with confirmatory testing since a
false-positive result for IgM can occur.
Several tests are used to help differentiate between
recently acquired infection and distant infections. The
IgG avidity test is one of the commonly used
confirmatory testings.
Results are based on the measurement of avidity of
functional affinity of toxoplasma-specific IgG
antibodies.
During an acute infection, IgG antibodies bind antigen
weakly (low avidity).
However, in chronic infection the affinity of IgG
anibodies increases progressively over weeks to months
(high avidity) (7). The currently available
avidity tests are helpful primarily in excluding that a
patient’s infection occurred within the prior 3-5
months.
This is most helpful in pregnant women in their first
months of gestation who have positive test result for
both IgG and IgM antibodies.
A
pregnant woman in her first trimester with high avidity
test result indicates the acute infection was not
acquired in the preceding 3 months and therefore the
fetus is at no risk of getting infected (8).
It should be noted that low avidity test result doesn’t
indicate recently acquired infection.
Avidity IgG testing should not be used alone as a
definitive test for decision making.
It
should be used with other serologic tests.
These tests are ELISA for IgM, IgA, IgE, IgG and the
differential agglutination test (7).
When the diagnosis of acute acquired T. gondii
infection during pregnancy has been established,
diagnostic efforts should focus on determining whether
the fetus has been infected.
However, these confirmatory tests might be available in
resources poor countries with high prevalence of
toxoplasmosis.
In
this situation, knowing the serologic status of the
patient at first prenatal examination in early pregnancy
might be helpful to differentiate between infection
before and during gestation.
A
screening program for toxoplasmosis in all pregnant
women can be implemented to institute preventive
measures for seronegative women and to ensure early
diagnosis and treatment of infection acquired during
pregnancy.
All
women who become pregnant should be serologically
screened in the first prenatal examination during her
first trimester, if found to be negative initially,
should be tested again during the second and third
trimesters.
In
addition, women are educated about prevention methods
during pregnancy.
Women with Toxoplasma infections are treated as
soon as infection is detected (9).
Congenital toxoplasmosis in the fetus:
Prenatal diagnosis of fetal infection is recommended
when a diagnosis of acute infection is established or
highly suspected in a pregnant woman.
Prenatal diagnosis of congenital toxoplasmosis is based
on ultrasonography and amniocentesis.
PCR on amniotic fluid for the detection of T. gondii-specific
DNA performed at 18 week of gestation or later is more
sensitive, more rapid, and safer than conventional
diagnostic procedures involving fetal blood sampling.
Amniotic fluid should be tested by PCR in all cases with
serologic test results diagnostic of or highly
suggestive of acute acquired infection during pregnancy
and if there is evidence of fetal damage by ultrasound
examination such as hydrocephalus or calcifications
(10).
Congenital toxoplasmosis in the newborn:
Serologic diagnosis of congenital toxoplasmosis in the
newborn is most commonly made by demonstration of serum
IgM or IgA Toxoplasma gondii antibodies in the
infant.
The serologic diagnosis can not be made by
demonstration of IgG antibodies in the newborn because
of maternal IgG antibodies are passively transferred in
utero to the fetus.
However, transmission of maternal IgM and/or IgA
antibodies can occur during the birth process.
Therefore, serum samples obtained from peripheral blood
and not from the umbilical cords are preferred.
Furthermore, positive results for IgM and IgA antibodies
in the newborn must be confirmed by repeat testing at
2-4 days of life in the case of IgM antibodies and at 10
days of life for IgA antibodies (11).
Occasionally, some newborn with congenital toxoplasmosis
may be negative for IgM and/or IgA antibodies during the
newborn period.
In this case, a monthly measurement of infant IgG
antibodies should be performed for 6 months or longer to
determine if IgG antibodies are due maternal transfer of
antibodies or to the infant’s own immune response to the
infection (12). Studies using the Western
blot techniques, with IgG and IgM mother-infant pairs,
have shown that maternal and infant sera may recognize
different T. gondii antigens when the infant is
congenitally infected.
However, it should be emphasized that Western blot
method should be used in a combination with other
serologic testing.
Overall, the combination of Western blots with
conventional serologic tests can detect 94% of
congenitally infected infants in the first 3 months of
life (7).
PCR of cerebrospinal fluid, whole blood, and urine can
also be used to diagnose congenital toxoplasmosis in the
newborn (6).
Finally, evaluation of infants with suspected congenital
toxoplasmosis always should include ophthalmologic
examination, radiologic examination for detection o
cerebral calcifications, and examination of
cerebrospinal fluid (6).
T. gondii infection in immunocompromised patient:
Reactivation of chronic infection is the most common
source of toxoplasmosis in immunocompromised patients
such as patients with AIDS, malignancy, and organ
transplantation.
Routine screening of these patients for T. gondii
IgG antibodies should be as an initial assessment.
Patient with negative IgG antibodies should be
instructed on prevention of infection.
Patient with positive IgG antibodies are at high risk
of reactivation.
Post-transplant serology frequently is not helpful in
the diagnosis of toxoplasmosis in patients who have
undergone organ transplantation and knowing the
pre-transplant serology status might be helpful. A
definitive diagnosis of toxoplasmosis in
immunocompromised patients relies on histologic
demonstration of the parasite or on detection of T.
gondii DNA by PCR (4).
Ocular toxoplasmosis:
In
most cases, toxoplasma chorioretinitis is diagnosed by
ophthalmologic examination, and empiric therapy against
T. gondii is often initiated based on clinical
findings and serologic test result.
However, in cases of unclear diagnosis or inadequate
clinical response to empiric therapy, other diagnostic
tests such as abnormal T. gondii antibody
response in ocular fluid, histopathologic examination,
and PCR of vitreous or aqueous fluids should be used
(13).
Treatment
Treatment of toxoplasmosis in immunocompetent persons
other than pregnant women is generally not indicated
unless symptoms are severe or persistent.
In
immunocompromised persons, treatment usually consists of
pyrimethamine,sulfadiazine, and folinic acid.
Depending on gestational age and whether the fetus is
known to be infected, pregnant women have been treated
with the antibiotic spiramycin or with sulfadiazine
alone or the combination of pyrimethamine and
sulfadiazine (14).
Treatment of acute infection during pregnancy has been
associated with an approximately 50% reduction in fetal
infection (15). Treatment options for
toxoplasmosis are summarized in table2.
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