Toxoplasmosis
B. Denise Hemby and Theresa M. Campo
Definition
A.Toxoplasmosis is caused by an intracellular protozoan parasite, Toxoplasma gondii. Cats are the primary host in which T. gondii can complete its reproductive cycle. Humans are the intermediate host. Toxoplasmosis is acquired through contact with infected cat feces (cleaning a cat’s litter box), by eating raw or undercooked meat (usually pork, lamb, goat, or wild game meat), by gardening, or by eating soil-contaminated fruit or vegetables. In less developed countries, contaminated unfiltered water is an important source of infection. Once ingested by humans or any other warm-blooded animal, the parasite transforms into a tissue-infective stage in the intestine, migrates through the intestinal wall, and is carried via the blood to other tissues, including the central nervous system (CNS). Mother-to-child transmission typically occurs when a pregnant woman is newly infected during or just prior to her pregnancy. The organism can also be transmitted when a previously uninfected person receives an organ or blood transfusion from an infected donor.
B.Emphasis should not be placed on prior exposure to cats, because patients can acquire toxoplasma without direct contact with felines. Toxoplasmosis is one of the TORCH infections (Toxoplasmosis, Other infections including syphilis, Rubella, CMV, and herpes simplex virus [HSV]). Toxoplasmosis causes CNS disease in patients with AIDS and has perinatal consequences. Latent infection can persist for the life of the host.
C.There are three genotypes of T. gondii: types I, II, and III. Genotype II is generally responsible for congenital toxoplasmosis in the United States.
D.There is no vaccination available for the prevention of toxoplasmosis.
Incidence
A.Toxoplasmosis has a worldwide distribution and is responsible for considerable morbidity and mortality in the United States. Serologic evidence of infection is more frequently seen in black and Hispanic persons, and among persons who are foreign-born, have low educational levels or socioeconomic status, or have occupations involving exposure to soil. There is no association with cat ownership. The incidence of seropositivity in adults ranges from 9% (United States) to 85% (Europe). Adults most commonly acquire toxoplasmosis by environmental exposure, that is, through ingestion of infectious oocysts, usually from soil contamination with feline feces.
B.Once a person is infected, the parasite lies dormant in neural and muscle tissue and will never be eliminated. Studies have now revealed associations between T. gondii antibody seropositivity (indicating infection) and the presence of various psychiatric disorders in humans (e.g., schizophrenia, bipolar illness, suicide attempts, episodes of self-directed violence, and memory impairment in elderly persons). Approximately 50% of all pregnant women in the United States have been previously infected and are immune, whereas those who keep cats as pets have a higher seropositivity rate. Congenital infection can cause pregnancy loss (miscarriage or stillbirth) or severe disease in the newborn, including developmental delays, blindness, and epilepsy. However, many newborns with congenital toxoplasmosis are asymptomatic at birth. Nevertheless, even if asymptomatic at birth, illness will develop in many infected infants later in their life, most often ocular disease but also neurologic symptoms and developmental disabilities.
C.Approximately 30% of women who acquire the infection during pregnancy transmit the infection to the fetus; the risk of transmission from mother to child is lowest when infection occurs during the first trimester (10%–15%) and higher as pregnancy progresses to the third trimester (60%–90%)
D.In the United States, it is estimated that toxoplasmosis is the second leading cause of death attributable to a foodborne illness. It is also the fourth leading cause of hospitalizations from contaminated food and the leading contributor to loss of quality-adjusted life years. T.gondii infects an estimated 1.1 million persons each year in the United States.
E.In patients with late phase HIV infection and AIDS, toxoplasmosis is the leading cause of focal CNS disease.
Pathogenesis
A.T. gondii is the causative agent and an intracellular protozoan parasite. It is worldwide in distribution; cats, birds, and domesticated animals serve as reservoirs. T. gondii is recognized as a major cause of opportunistic infection in AIDS.
B.The incubation period is estimated to be on average 7 days (4- to 21-day range).
C.Routine screening for toxoplasmosis in pregnancy is not currently recommended:
1.Maternal toxoplasmosis infection is acquired orally.
2.Fetal infection results from transmission of parasites via the placenta (vertical transmission).
3.Neonatal infection may also occur during vaginal delivery.
Predisposing Factors
A.Food sources:
1.Eating raw or undercooked meats, especially lamb, goat, pork, and wild game meat.
2.Drinking unpasteurized goat milk.
3.Eating raw shellfish from contaminated waters.
B.Exposure to contaminated soil or gardens, kitty litter, and cats.
C.Immunocompromised state:
1.HIV-infected/AIDS.
2.Cancer therapy.
3.Transplant recipients.
4.Prescribed immunosuppressive drugs.
D.T. gondii has been documented as being acquired from blood or blood product transfusion and organ (i.e., heart) or bone-marrow transplant from a seropositive donor with latent infection.
E.Poor sanitary conditions.
F.Consumption of contaminated unfiltered water.
G.Occupational exposure:
1.Working with meat.
2.Landscaping.
H.Travel to underdeveloped country.
Common Complaints
A.80% to 90% of acute T. gondii infectious hosts are asymptomatic.
B.Bilateral, symmetrical, nontender cervical adenopathy.
C.30% of symptomatic patients have generalized lymphadenopathy.
Other Signs and Symptoms
A.Usually subclinical infection:
1.Fever.
2.Arthralgia, malaise, and myalgia.
3.Headache.
4.Sore throat/pharyngitis.
5.Generalized lymphadenopathy.
6.Skin rash: Diffuse nonpruritic maculopapular rash.
7.Hepatosplenomegaly.
8.Chorioretinitis: Ocular pain and loss of visual acuity (most frequent, permanent manifestation of toxoplasmic infection).
B.Pregnancy:
1.Intrauterine growth restriction (IUGR) or low birth weight.
2.Hydrocephaly.
3.Microcephaly.
4.Anemia.
C.CNS toxoplasmosis:
1.Headache, dull and constant, is an almost universal symptom of cerebral lesions in AIDS patients.
2.Fever.
3.Lethargy.
4.Altered mental state.
5.Seizures.
6.Weakness.
7.Hemiparesis.
8.Cranial nerve disturbances.
9.Sensory abnormalities.
10.Movement disorders.
11.Neuropsychiatric manifestations: Toxoplasmosis is a significant factor in the causation of mental retardation and blindness.
Subjective Data
A.Review onset, course, and duration of symptoms.
B.Determine if the patient is pregnant.
C.Review presence of indoor cat and contact with cat litter.
D.Rule out other illness with review of symptoms such as pharyngitis (mononucleosis).
E.Elicit initial site of rash and progression to other body areas.
F.Determine any new medications and contact exposures.
G.Rule out other family members with similar symptoms.
H.Review HIV status.
I.Review ingestion of raw/rare or undercooked meats, raw shellfish, and unpasteurized goat’s milk.
J.Review recent travel to an underdeveloped country (untreated water).
K.Review occupational exposure.
Physical Examination
A.Check temperature, pulse, respirations, and blood pressure.
B.Inspect:
1.Conduct ear, nose, and throat exam and careful funduscopic exam.
A funduscopic exam may reveal yellow-white areas of retinitis with fluffy borders. Diagnosis of ocular toxoplasmosis is based on observation of characteristic retinal lesions in conjunction with toxoplasma-specific serum immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies.
2.Complete a dermal exam.
C.Auscultate: Auscultate lungs and heart.
D.Palpate:
1.Palpate all lymph nodes, especially cervical nodes. Lymph nodes are usually smaller than 3 cm in size and nonfluctuant.
2.Palpate the abdomen.
3.Palpate the joints.
E.Neurologic exam: Conduct a mental status evaluation.
Diagnostic Tests
A panel of tests (the toxoplasma serological profile [TSP]) consisting of the Sabin-Feldman dye test (DT), double sandwich immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA), IgA ELISA, IgE ELISA, and differential agglutination (AC/HS), and avidity test. The most commonly used tests for the measurement of IgG antibody are the DT, the ELISA, the immunofluorescence assay (IFA), and the modified direct agglutination tests. PCR amplification is used for detection of DNA in body fluids and tissue for the diagnosis of congenital, ocular, and cerebral and disseminated toxoplasmosis:
A.DT—high titers; positive IgM, IgA, and IgE ELISAs and an acute pattern in the AC/HS test are highly suggestive of a recently acquired infection.
B.IgG antibodies—usually appear within 1 to 2 weeks of acquisition of the infection, peak within 1 to 2 months, decline at various rates and usually persist for life.
C.IgE antibodies—detected by ELISA for acutely infected adults, congenitally infected infants, and children with congenital toxoplasmic chorioretinitis.
D.PCR—often performed on amniotic fluid at 18 gestation weeks to determine if infant is infected:
1.Complete blood count (CBC) with differential.
2.HIV (rule out).
3.Pregnancy test if indicated.
4.CT scan or MRI (usually superior to CT scan).
Differential Diagnoses
A.Toxoplasmosis.
B.Epstein–Barr virus (EBV).
C.Cytomegalovirus (CMV) retinitis.
D.Cat scratch disease (CSD).
E.Tuberculosis.
F.Syphilis.
G.Sarcoidosis.
H.Hodgkin’s disease.
I.Lymphoma.
J.Viral syndrome.
K.HIV.
L.Mononucleosis.
M.Pneumocystis carinii pneumonia.
N.Varicella zoster.
O.Fungal infection of eye.
Plan
A.Patient teaching: Handwashing is the single most important measure to reduce transmission of T. gondii. 
See Section III: Patient Teaching Guide Chlamydia
:
B.Pharmaceutical therapy:
1.Treatment is rarely necessary because most clinical illness resolves spontaneously; the exception is during pregnancy.
2.Treatment is usually given for 2 to 4 weeks if disease is clinically evident or symptoms are severe or persistent. If ocular lesions are present the patient should be immediately referred to ophthalmology for evaluation and treatment:
a.Nonpregnant adults: One of two regimens are typically prescribed:
i.Pyrimethamine: 100 mg loading dose then 25 to 50 mg by mouth daily; plus sulfadiazine 2 to 4 g/d by mouth in divided doses; plus leucovorin calcium (folinic acid) 10 to 25 mg by mouth daily. Pyrimethamine penetrates the brain parenchyma efficiently even in the absence of inflammation. Leucovorin reduces the likelihood of development of hematologic toxicities associated with pyrimethamine therapy.
ii.Pyrimethamine: 100 mg loading dose, then 25 to 50 mg by mouth daily; plus clindamycin 300 mg by mouth four times a day; plus leucovorin calcium (folinic acid) 10 to 25 mg by mouth daily. (Pyrimethamine plus clindamycin plus leucovorin is the preferred alternative regimen for patients who cannot tolerate sulfadiazine or do not respond to first-line therapy.)
b.Maternal and fetal-Spiramycin is recommended for the first and early second trimesters or pyrimethamine/sulfadiazine and leucovorin for late second and third trimesters.