Toxoplasmosis

• Toxoplasma gondii, an obligate intracellular protozoan, is

acquired perorally, transplacentally, or, rarely, parenterally in
laboratory accidents; by transfusion; or from a transplanted
organ
• T. gondii is a coccidian protozoan that multiplies only in living
cells. The tachyzoites are oval or crescent-like, measuring 2–4
× 4–7 μm. Tissue cysts, which are 10–100 μm in diameter, may
contain thousands of parasites and remain in tissues, especially
the CNS and skeletal and heart muscle, for the life of the host.
Toxoplasma can multiply in all tissues of mammals and birds.
• Newly infected cats excrete infectious Toxoplasma
oocysts in their feces. Toxoplasma organisms are
transmitted to cats by ingestion of infected meat
containing encysted bradyzoites or by ingestion of
oocysts excreted by other recently infected cats. The
parasites then multiply through schizogonic and
gametogonic cycles in the distal ileal epithelium of the
cat intestine. Oocysts containing 2 sporocysts are
excreted, and, under proper conditions of temperature
and moisture, each sporocyst matures into 4
sporozoites. For about 2 wk the cat excretes 105–107
oocysts/day, which, in a suitable environment, may
retain their viability for >1 yr. Oocysts sporulate 1–5
days after excretion and are then infectious.
• Oocysts are killed by drying or boiling, but not exposure
to bleach., Oocysts and tissue cysts are sources of
animal and human infections
 Human infection is usually acquired
orally by eating undercooked or raw
meat that contains cysts or food or
other material contaminated with
oocysts from acutely infected cats.
 Freezing meat to -20°C or heating it to
66°C renders the cysts noninfectious..
 Toxoplasma organisms are not
transmitted from person to person
except for transplacental infection
from mother to fetus and, rarely, by
organ transplantation or transfusion.
 Congenital Toxoplasmosis
 Transmission to the fetus usually follows
acquisition of infection by an immunologically
normal mother during gestation.
 Congenital transmission from mothers
infected before pregnancy is extremely rare
except for immunocompromised women who
are chronically infected.
 The incidence of infection among pregnant
women depends on the general risk for
infection in the specific locale and the
proportion of the population that has not been
infected previously.
 PATHOGENESIS
 When a mother acquires infection during gestation, organisms
may disseminate hematogenously to the placenta. Of
untreated maternal infections acquired in the 1st trimester,
approximately 17% of fetuses are infected, usually with
severe disease. Of untreated maternal infection acquired in
the 3rd trimester, approximately 65% of fetuses are
infected, usually with disease that is mild or inapparent at
birth. These different rates of transmission and outcomes are
most likely related to placental blood flow, virulence, inoculum
of T. gondii, and immunologic capacity of the mother to limit
parasitemia.
 Examination of the placenta of infected newborns may reveal
chronic inflammation and cysts. Tachyzoites can be seen with
Wright or Giemsa stains but are best demonstrated with
immunoperoxidase technique. Tissue cysts stain well with
periodic acid-Schiff and silver stains as well as with the
immunoperoxidase technique.
 Gross or microscopic areas of necrosis may be present in
many tissues, especially the CNS, choroid and retina, heart,
lungs, skeletal muscle, liver, and spleen. Areas of calcification
occur in the brain.
 CLINICAL MANIFESTATIONS
 Congenital toxoplasmosis usually occurs when a woman
acquires primary infection while pregnant. Most often,
maternal infection is asymptomatic or without specific
symptoms or signs. As with other adults with acute
toxoplasmosis, lymphadenopathy is the most common
symptom, but this is present in only a small subset of
mothers
 Congenital infection may present as a mild or severe
neonatal disease, with onset during the 1st mo of life or
with sequelae or relapse of a previously undiagnosed, and
untreated, infection presenting during infancy or even later
in life.
 There is a wide variety of manifestations of congenital
infection ranging from hydrops fetalis and perinatal death
to small size for gestational age, prematurity, peripheral
retinal scars, persistent jaundice, mild thrombocytopenia,
CSF pleocytosis, and the characteristic triad of
chorioretinitis, hydrocephalus, and cerebral calcifications.
 Neurologic signs such as convulsions, setting-sun sign with
downward gaze, and hydrocephalus with increased head
circumference may be associated with or without
substantial cerebral damage, or with relatively mild
inflammation obstructing the aqueduct of Sylvius. If
affected infants are treated promptly, signs and symptoms
may resolve and they may develop normally.
 Diagnosis
 General and Pregnant Women
 Because toxoplasmosis can only rarely be documented by the
observation of parasites in patient specimens, antibody detection tests
are the main source of diagnostic information. More commonly available
tests include enzyme immunoassays (EIAs), agglutination tests, and
indirect fluorescent antibody (IFA) tests. Positive immunoglobulin (Ig) G
antibody tests are indicative of an infection occurring in the past,
whereas positive IgM antibody tests indicate an infection occurring more
recently. However, some IgM antibody tests can stay positive for 18
months or more, or give false-positive reactions.
 When clinicians are attempting to determine whether or not T. gondii
infection occurred in a woman during her pregnancy, a serologic profile
done in a reference laboratory—including the avidity test, differential
agglutination, Sabin-Feldman dye test, IgM EIA, IgA EIA, and IgE EIA,
and, if indicated, repeat titers—is helpful in attempting to determine the
timing of infection. Serologic diagnosis must be confirmed at a reference
laboratory before potentially toxic drugs or amniocentesis for T. gondii
infection diagnosis are considered for a pregnant woman.
 When serologic test results indicate a potential T. gondii infection during
pregnancy, diagnosis of congenital toxoplasmosis in the fetus is usually
accomplished by amniocentesis and DNA polymerase chain reaction
(PCR) testing of amniotic fluid at a reference laboratory from 18 weeks
of gestation onward.
 Infants
 In the newborn, diagnosis of Toxoplasma infection is made with a
combination of serologic testing (IgG, IgM, and IgA antibodies), parasite
isolation, and evaluation of cerebrospinal fluid (CSF) (glucose, protein,
cells, total IgG antibody, Toxoplasma-specific IgG and IgM antibodies, and
direct examination for tachyzoites). In addition, an infant suspected of
having congenital toxoplasmosis should have a thorough general,
neurologic, and ophthalmologic examination and a CT scan of the head.
Positive Toxoplasma-specific IgM or IgA is diagnostic of congenital
infection. Although occasionally placental leak can lead to a false-positive
IgM test in the infant, repeat testing in approximately 10 days can help
resolve the diagnosis because the half-life of IgM is only 3 to 5 days.
Maternal IgG antibodies in the newborn's peripheral blood reflect infection
in the mother; however, persistent or increasing IgG antibody levels in
the infant compared with the mother measured by the dye test or IFA test
provide strong evidence of congenital infection. Persistence of a positive
IgG test result in the infant beyond 1 year of life confirms congenital
infection, whereas a negative IgG test at 1 or more years of age
essentially rules out congenital infection.
 Demonstration of serum antibodies in the newborn that are directed
against unique Toxoplasma epitopes on immunoblot that are not found in
the mother provides diagnostic evidence for congenital infection. In
addition, direct demonstration of the parasite by isolation (mouse
inoculation or tissue culture) and amplification of T. gondii–specific DNA
(e.g., PCR of CSF, peripheral blood, or urine) are used to diagnose
infection in infants. Infants born to women who have serologic evidence of
infections with human immunodeficiency virus (HIV) and Toxoplasma
should be evaluated for congenital toxoplasmosis.
 TREATMENT
 Pyrimethamine plus sulfadiazine act synergistically against
Toxoplasma, and combination therapy is indicated for many of the
forms of toxoplasmosis. However, use of pyrimethamine is
contraindicated during the 1st trimester of pregnancy.
 Spiramycin should be used to attempt to prevent vertical
transmission of infection to the fetus of acutely infected pregnant
women, and to treat congenital toxoplasmosis.
 Pyrimethamine inhibits the enzyme dihydrofolate reductase
(DHFR), and thus the synthesis of folic acid, and therefore
produces a dose-related, reversible, and usually gradual
depression of the bone marrow, resulting in thrombocytopenia,
leukopenia, and anemia. Reversible neutropenia is the most
common adverse effect in treated infants. All patients treated with
pyrimethamine should have platelet and leukocyte counts twice
weekly.
 Seizures may occur with overdosage of pyrimethamine. Folinic
acid, as calcium leukovorin, should always be administered
concomitantly and for 1 wk after treatment with pyrimethamine is
discontinued to prevent bone marrow suppression. Potential toxic
effects of sulfonamides (e.g., crystalluria, hematuria, and rash)
should be monitored. Hypersensitivity reactions occur, especially
in patients with AIDS.
 Congenital Toxoplasmosis
 All newborns infected with T. gondii should be treated
whether or not they have clinical manifestations of the
infection because treatment may be effective in
interrupting acute disease that damages vital organs.
 Infants should be treated for 1 yr with pyrimethamine
(2 mg/kg/day for 2 days, then 1 mg/kg/day for 2 or 6
mo, then 1 mg/kg given on Monday, Wednesday, and
Friday, or more often, PO), sulfadiazine (100
mg/kg/day divided bid PO), and leukovorin (5–10 mg
given on Monday, Wednesday, and Friday, PO).

 Pyrimethamine and sulfadiazine are available only in

tablet form and can be prepared as suspensions.
 Prednisone (1 mg/kg/day divided bid PO) has been
utilized in addition when active chorioretinitis involves
the macula or otherwise threatens vision or the CSF
protein is >1,000 mg/dL at birth, but the efficacy is
not established.
 .Pregnant Women with T .gondii Infection
 The immunologically normal pregnant woman who acquired T. gondii
before conception does not need treatment to prevent congenital infection
of her fetus.
 Treatment of a pregnant woman who acquires infection at any time during
pregnancy reduces the chance of congenital infection in her infant.
Spiramycin (1 g every 8 hr PO without food) is recommended for
prevention of fetal infection if the mother develops acute Toxoplasmosis
during pregnancy.
 Adverse reactions are infrequent and include paresthesias, rash, nausea,
vomiting, and diarrhea.
 Pyrimethamine (50 mg once daily PO), sulfadiazine (2 g bid PO), and
leukovorin (10 mg once daily PO) are recommended for confirmed or
probable fetal infection except in the 1st trimester, when spiramycin is
recommended because pyrimethamine is potentially teratogenic.
 Delay in maternal treatment during gestation results in greater brain and
eye disease in the infant.
 Diagnostic amniocentesis should be performed at >17–18 wk of gestation
in pregnancies when there is high suspicion of fetal infection.
 Chronically infected pregnant women who are immunocompromised have
transmitted T. gondii to their fetuses. Such women should be treated with
spiramycin throughout gestation.
 PREVENTION
 Counseling pregnant women about the methods of
preventing transmission of T. gondii during pregnancy
can substantially reduce acquisition of infection during
gestation.
 Women who do not have specific antibody to T. gondii
before pregnancy should only eat well-cooked meat
during pregnancy and avoid contact with oocysts
excreted by cats.
 Cats that are kept indoors, maintained on prepared
food, and not fed fresh, uncooked meat should not
contact encysted T. gondii or shed oocysts.
 Serologic screening, ultrasound monitoring, and
treatment of pregnant women during gestation can
also reduce the incidence and manifestations of
congenital toxoplasmosis.
 No protective vaccine is available.